Polymorphism of SMAD7 gene (rs2337104) and risk of colorectal cancer in an Iranian population: a case-control study

PubMed Central

Akbari, Zahra; Safari-Alighiarloo, Nahid; Taleghani, Mohammad Yaghoob; Mirfakhar, Farzaneh Sadat; Asadzadeh Aghdaei, Hamid; Vahedi, Mohsen; Irani Shemirani, Atena; Nazemalhosseini-Mojarad, Ehsan; Zali, Mohammad Reza

2014-01-01

Aim: The purpose of this study was to evaluate the influence of intronic polymorphism of the SMAD7 (Mothers Against Decantaplegic Homolog 7) gene (rs2337104) on the risk of colorectal cancer (CRC) and clinicopathological features in an Iranian population. Background: SMAD7 has been identified as an antagonist of transforming growth factor beta (TGF-b)-mediating fibrosis, carcinogenesis, and inflammation. Regarding to the recent genome-wide scan, a risk locus for colorectal cancer at 18q21 has been found, which maps to the SMAD7 gene. Patients and methods: This case-control study was performed on 109 CRC patients and 109 healthy controls recruited in Taleghani Hospital. The genotyping of all samples were done by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from peripheral blood. The association of this polymorphism with the risk of CRC and clinicopathological features was investigated. Results: Our results indicated that there were no significant association between genotypic and allelic frequencies of SMAD7 polymorphism (rs2337104) and CRC risk in our population. Although the T allele is the most frequent one in this population and its frequency was 86.7% in patients compared with 91.7% in controls (OR=1.705, 95% CI= 0.916–3.172). Also, the SMAD7 genotypes were not associated with any clinicopathological characteristics in CRC patients (P>0.05). Conclusion: For the first time, this study results revealed that this SMAD7 polymorphism couldn’t be a potential risk factor for CRC or a prognostic biomarker for prediction of clinicopathological features in an Iranian population. A large-scale case-control study is needed to validate our results. PMID:25289133

A retrospective clinico-pathological study comparing lichen planus pigmentosus with ashy dermatosis.

PubMed

Cheng, Hui Mei; Chuah, Sai Yee; Gan, Emily Yiping; Jhingan, Anjali; Thng, Steven Tien Guan

2018-04-10

Controversy persists as to whether lichen planus pigmentosus and ashy dermatosis are separate clinical entities. This study was conducted to examine the clinicopathological features and treatment outcome of the two conditions. A retrospective medical chart review of all patients who were diagnosed with lichen planus pigmentosus or ashy dermatosis was conducted. The information collected included the participants' age at onset, site of onset, duration of disease, presence of precipitating factors, distribution of disease, pigmentation and presence of symptoms. In patients from whom a biopsy was taken the histopathological reports were included. Altogether 26 patients with ashy dermatosis and 29 with lichen planus pigmentosus were included in the study. Compared with ashy dermatosis, lichen planus pigmentosus had a more localised distribution with a preponderance for facial involvement, compared with the truncal preponderance in ashy dermatosis. Ashy dermatosis tended to have a more stable clinical course than lichen planus pigmentosus, which was more likely to wax and wane. The utility of histopathology in differentiating between the two conditions is low. Ashy dermatosis and lichen planus pigmentosus, as defined in this study, appear to be two separate clinical entities with distinguishable clinical features and natural histories. © 2018 The Australasian College of Dermatologists.

"Clinicopathological features and treatment outcomes of differentiated thyroid cancer in Saudi children and adults".

PubMed

Al-Qahtani, Khalid Hussain; Tunio, Mutahir A; Al Asiri, Mushabbab; Aljohani, Naji J; Bayoumi, Yasser; Riaz, Khalid; AlShakweer, Wafa

2015-11-06

Age is an important prognostic factor in differentiated thyroid cancer (DTC). Our aim was to evaluate differences in clinicopathological features and treatment outcomes among children and adult patients with DTC. We studied 27 children (below 18 years) with DTC treated during the period 2000-2012 and were compared with (a) 78 adults aged 19-25 years and (b) 52 adults aged 26-30 years treated during the same period in terms of their clinicopathological features and long term treatment outcomes. Locoregional recurrence (LRR), locoregional control (LRC), distant metastasis (DM), distant metastasis control (DMC), disease free survival (DFS) and overall survival (OS) rates were evaluated. Mean age of children was 13.5 years (range: 5-18), while mean age of adults was 24.6 years (range: 19-30). In children, female: male ratio was 2.85:1, and in adults female: male ratio was 7.1:1 (P = 0.041). No significant difference in tumor size was seen between the two groups (P = 0.653). According to American Thyroid Association (ATA) risk stratification classification, the children (85.2 %) were found to have at high risk as compared to adults P = 0.001. Post-thyroidectomy complications and RAI induced toxicities were observed more in children than adults (P = 0.043 and P = 0.041 respectively). LRR occurred in 6 (22.2 %), 9 (11.5 %) and 3 (5.8 %) in age groups of <18 years, 19-25 years and 26-30 years respectively (P = 0.032); while DM was seen in 10 (37.0 %), 9 (10.3 %) and 5 (9.6 %) in age groups of <18 years, 19-25 years and 26-30 years respectively (P = 0.002). Ten year DFS rates were 67.3 % in age group below 18 years, 82.4 % in age group of 19-25 years and 90.1 % in age group of 26-30 years (P = 0.021). At the time of diagnosis, children with DTC were found to have more aggressive clinicopathological characteristics. Comparatively lower LRC, DMC and DFS rates in children warrants further multi-institutional studies.

Clinicopathological characteristics of clinical early gastric cancer in the upper-third stomach.

PubMed

Ichikawa, Daisuke; Komatsu, Shuhei; Kosuga, Toshiyuki; Konishi, Hirotaka; Okamoto, Kazuma; Shiozaki, Atsushi; Fujiwara, Hitoshi; Otsuji, Eigo

2015-12-07

To elucidate the clinicopathological characteristics of clinically early gastric cancer in the upper-third stomach and to clarify treatment precautions. A total of 683 patients with clinical early gastric cancer were enrolled in this retrospective study, 128 of whom had gastric cancer in the upper-third stomach (U group). All patients underwent a double contrast barium examination, endoscopy, and computed tomography (CT), and were diagnosed preoperatively based on the findings obtained. The clinicopathological features of these patients were compared with those of patients with gastric cancer in the middle- and lower-third stomach (ML group). We also compared clinicopathological factors between accurate-diagnosis and under-diagnosis groups in order to identify factors affecting the accuracy of a preoperative diagnosis of tumor depth. Patients in the U group were older (P = 0.029), had a higher ratio of males to females (P = 0.015), and had more histologically differentiated tumors (P = 0.007) than patients in the ML group. A clinical under-diagnosis occurred in 57 out of 683 patients (8.3%), and was more frequent in the U group than in the ML group (16.4% vs 6.3%, P < 0.0001). Therefore, the rates of lymph node metastasis and lymphatic invasion were slightly higher in the U group than in the ML group (P = 0.071 and 0.082, respectively). An under-diagnosis was more frequent in histologically undifferentiated tumors (P = 0.094) and in those larger than 4 cm (P = 0.024). The median follow-up period after surgery was 56 mo (range, 1-186 mo). Overall, survival and disease-specific survival rates were significantly lower in the U group than in the ML group (P = 0.016 and 0.020, respectively). However, limited operation-related cancer recurrence was not detected in the U group in the present study. Clinical early gastric cancer in the upper-third stomach has distinguishable characteristics that increase the risk of a clinical under-diagnosis, especially in patients with larger or undifferentiated tumors.

[Expression of SLP-2 protein in esophageal squamous cell carcinoma is associated with cancer invasion].

PubMed

Cao, Wen-feng; Zhang, Li-yong; Zhang, Bin; Wang, Yue-qi; Liu, Zhi-hua; Sun, Bao-cun

2010-11-01

To study the expression of stomatin-like protein-2 (SLP-2) in esophageal squamous cell carcinoma (ESCC), and analyze the correlation between SLP-2 expression and clinicopathological features. The expression of SLP-2 protein in ESCC tissues (18 and 220 cases respectively) was detected by Western blot and IHC. The association between SLP-2 expression and clinicopathological features was analyzed. Compared with normal epithelium, 13 cases of ESCC tissues showed a higher expression of SLP-2 on the protein level (72.2%, 13/18). IHC analysis on tissue microarray revealed that the expression rate of SLP-2 protein in ESCC was 54.1% and in normal esophageal mucosa was 3.6%, showing a significant difference (P < 0.001). SLP-2 high-level expression correlates with the extent of ESCC invasion (P = 0.033), but not with other clinicopathologic characteristics (P > 0.05). SLP-2 as a novel cancer-related gene may play an important role in tumorigenesis of ESCC. The overexpression of SLP-2 may be closely associated with the invasion of esophageal cancer.

Clinical significance of Mena and Her-2 expression in breast cancer.

PubMed

Du, J W; Xu, K Y; Fang, L Y; Qi, X L

2012-01-01

The aim of this study was to determine the expression patterns of Mena and Her-2 in breast cancer tissues and to explore their clinical significance and correlation with clinicopathological parameters. The expression of Mena and Her-2 was detected in 40 breast cancer tissues and 14 normal breast tissues by immunohistochemistry, and the relationship of Mena and Her-2 expression with clinicopathological parameters was analyzed. Both Mena (70%) and Her-2 (40%) were more commonly expressed in breast cancer than in normal breast tissue (7.1%, 0%, respectively; p < 0.05); further, Mena and Her-2 expression in breast cancer were positively correlated (r = 0.530, p < 0.05). In comparing expression with clinicopathological parameters of tumor samples, Mena and Her-2 were both associated with axillary lymph node metastasis and TNM stage (p < 0.05), but not with patient age or pathological type. Mena and Her-2 are related to the malignancy degree and metastasis of breast cancer, and thus may play a coordinating role in the occurrence and progression of breast cancer.

The clinicopathologic differences in papillary thyroid carcinoma with or without co-existing chronic lymphocytic thyroiditis.

PubMed

Yoon, Yeo-Hoon; Kim, Hak Joon; Lee, Jin Woo; Kim, Jin Man; Koo, Bon Seok

2012-03-01

The goal of this study is to determine the clinicopathologic differences in patients with papillary thyroid carcinoma (PTC) with or without chronic lymphocytic thyroiditis (CLT). We reviewed the medical records of 195 consecutive PTC patients who underwent total thyroidectomy and bilateral central lymph node dissection from April 2008 to March 2010. The differences in clinicopathologic factors, such as age, gender, size of primary tumor, perithyroidal invasion, lymphovascular invasion, capsular invasion, and central lymph node (CLN) metastasis, were analyzed in PTC patients with or without CLT. Among 195 patients, 56 (28.7%) had co-existing CLT. Patients with CLT had the following characteristics as compared to patients without CLT: significantly younger, female predominance, smaller tumor size, and lower incidence of capsular invasion (p = 0.038, 0.006, 0.037, and 0.026, respectively). Also, patients with CLT (12.5%) had a significantly lower incidence of CLN metastases than patients without CLT (28.1%; p = 0.025) based on univariate analysis. Moreover, multivariate analysis showed that younger age (p = 0.042, odds ratio = 1.033) and female gender (p = 0.012, odds ratio = 6.865) are independent clinical factors in patients with CLT compared to patients without CLT. CLT was shown to be commonly associated with PTC. Compared to patients with PTC without CLT, patients with CLT were younger with a female predominance, which are the most important and well-known prognostic variables for thyroid cancer mortality.

Comparative Study of Hand-Sutured versus Circular Stapled Anastomosis for Gastrojejunostomy in Laparoscopy Assisted Distal Gastrectomy.

PubMed

Seo, Su Hyun; Kim, Ki Han; Kim, Min Chan; Choi, Hong Jo; Jung, Ghap Joong

2012-06-01

Mechanical stapler is regarded as a good alternative to the hand sewing technique, when used in gastric reconstruction. The circular stapling method has been widely applied to gastrectomy (open orlaparoscopic), for gastric cancer. We illustrated and compared the hand-sutured method to the circular stapling method, for Billroth-II, in patients who underwent laparoscopy assisted distal gastrectomy for gastric cancer. Between April 2009 and May 2011, 60 patients who underwent laparoscopy assisted distal gastrectomy, with Billroth-II, were enrolled. Hand-sutured Billroth-II was performed in 40 patients (manual group) and circular stapler Billroth-II was performed in 20 patients (stapler group). Clinicopathological features and post-operative outcomes were evaluated and compared between the two groups. Nosignificant differences were observed in clinicopathologic parameters and post-operative outcomes, except in the operation times. Operation times and anastomosis times were significantly shorter in the stapler group (P=0.004 and P<0.001). Compared to the hand-sutured method, the circular stapling method can be applied safely and more efficiently, when performing Billroth-II anastomosis, after laparoscopy assisted distal gastrectomy in patients with gastric cancer.

Young adult breast cancer patients have a poor prognosis independent of prognostic clinicopathological factors: a study from the Japanese Breast Cancer Registry.

PubMed

Kataoka, Akemi; Iwamoto, Takayuki; Tokunaga, Eriko; Tomotaki, Ai; Kumamaru, Hiraku; Miyata, Hiroaki; Niikura, Naoki; Kawai, Masaaki; Anan, Keisei; Hayashi, Naoki; Masuda, Shinobu; Tsugawa, Koichiro; Aogi, Kenjiro; Ishida, Takanori; Masuoka, Hideji; Iijima, Kotaro; Kinoshita, Takayuki; Nakamura, Seigo; Tokuda, Yutaka

2016-11-01

The aim of this study was to investigate whether young age at onset of breast cancer is an independent prognostic factor in patients from the Japanese Breast Cancer Registry, after adjustment of known clinicopathological prognostic factors. Of the 53,670 patients registered between 2004 and 2006 and surveyed after a 5-year follow-up prognosis, 25,898 breast cancer patients (48.3 %), who were obtained prognostic data, were examined. Clinicopathological factors were compared between young adult (YA; <35 years), middle-aged adult (MA; 35-50 years), and older adult (OA; >50 years) patients. Five-year disease-free survival (DFS) and overall survival (OS) rates were studied. YA patients were associated with an advanced TNM stage and aggressive characteristics (e.g. human epidermal growth factor receptor 2 (HER2)-positive or oestrogen receptor (ER)-negative breast cancers) compared to MA and OA patients (P < 0.001). The 5-year DFS and OS rates were 79.4 % and 90.8, 88.5 and 95.0 %, and 87.8 % and 91.6 % for YA, MA, and OA patients, respectively. From the multivariable regression analysis, young age at onset was confirmed as an independent prognostic factor for both DFS (hazard ratio 1.73, 95 % confidence interval 1.42-2.10; P < 0.001) and OS (hazard ratio 1.58, 95 % confidence interval 1.16-2.15; P = 0.004). Young age at onset is an independent negative prognostic factor in breast cancer. Further studies are required to develop new therapeutic strategies for YA breast cancer patients.

Clinicopathological Characteristics of Patients with Gastric Cancer according to the Expression of LIN28A.

PubMed

Park, Chan Hyuk; Lee, Jung Hwa; Lee, Na Keum; Lee, Yong Chan; Lee, Sang Kil

2016-09-15

Although LIN28A is known to potentially play a role in the oncogenesis of various cancers, whether LIN28A expression is a predictor of poor prognosis in patients with gastric cancer has not been fully explored. We sought to evaluate clinicopathological characteristics according to the expression of LIN28A in numerous gastric cancer tissue samples. LIN28A expression was evaluated by immunohistochemical (IHC) analysis of a tissue microarray comprising 288 gastric cancer tissues and 288 adjacent normal tissues. Clinicopathological characteristics, including overall survival, were compared according to LIN28A expression. The IHC staining score was lower for the cancer tissues than the normal tissues (p<0.001). However, no significant differences were observed in the clinicopathological characteristics between the low and high LIN28A expression groups. In addition, the 5-year overall survival rate did not differ between the two groups: 75.3% (95% confidence interval [CI], 69.3% to 81.7%) versus 71.6% (95% CI, 63.3% to 80.9%) for low versus high expression, respectively. The expression of LIN28A did not appear to play a distinct role in predicting the clinicopathological characteristics of patients with gastric cancer. In addition, LIN28A expression was not an independently associated factor for overall survival in patients with gastric cancer.

Clinicopathological factors associated with survival in patients with breast cancer brain metastasis.

PubMed

Li, Rong; Zhang, Kui; Siegal, Gene P; Wei, Shi

2017-06-01

Brain metastasis from breast cancer generally represents a catastrophic event yet demonstrates substantial biological heterogeneity. There have been limited studies solely focusing on the prognosis of patients with such metastasis. In this study, we carried out a comprehensive analysis in 108 consecutive patients with breast cancer brain metastases between 1997 and 2012 to further define clinicopathological factors associated with early onset of brain metastasis and survival outcomes after development of them. We found that lobular carcinoma, higher clinical stages at diagnosis, and lack of coexisting bone metastasis were significantly associated with a worse brain relapse-free survival when compared with brain-only metastasis. High histologic grade, triple-negative breast cancer, and absence of visceral involvement were unfavorable prognostic factors after brain metastasis. Furthermore, high histologic grade, advanced tumor stages, and lack of coexisting bone involvement indicated a worse overall survival. Thus, the previously established prognostic factors in early stage or advanced breast cancers may not entirely apply to patients with brain metastases. Furthermore, the prognostic significance of the clinicopathological factors differed before and after a patient develops brain metastasis. This knowledge might help in establishing an algorithm to further stratify patients with breast cancer into prognostically significant categories for optimal prevention, screening, and treatment of their brain metastasis. Copyright © 2017 Elsevier Inc. All rights reserved.

Colorectal adenocarcinoma with mucinous component: relation of MMP-13, EGFR, and E-cadherin expressions to clinicopathological features and prognosis.

PubMed

Foda, Abd Al-Rahman Mohammad; El-Hawary, Amira Kamal; Aziz, Azza Abdel

2015-06-01

The aim of this study was to compare colorectal adenocarcinoma with mucinous component, ordinary adenocarcinoma (OA) and mucinous adenocarcinoma (MA) regarding clinicopathological parameters, survival, EGFR, MMP-13, and E-cadherin. We studied tumor tissue specimens from 28 patients with adenocarcinoma with mucinous component, 47 with OA, and 56 with MA, who underwent radical surgery from January 2007 to January 2012 at the Gastroenterology Centre, Mansoura University, Egypt. High density manual tissue microarrays were constructed and immunohistochemistry for EGFR, MMP-13, and E-cadherin was done. Colorectal adenocarcinoma with mucinous component (AWMC) was significantly associated with more perineural invasion, lower EGFR, and MMP-13 expressions than OA, with no difference in E-cadherin expression. Conversely, only microscopic abscess formation was significantly more with colorectal AWMC than MC with no difference in EGFR, MMP-13 and E-cadherin expression between both groups. Colorectal AWMC showed a better survival than MA with no difference with OA. In a univariate analysis, EGFR, MMP-13, and E-cadherin expressions did not show a significant impact on disease-free or overall survival in patients with colorectal AWMC. Colorectal AWMC remains a vague entity that resembles OA in some clinicopathological and molecular respects as well as MA. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Clinicopathological features and pituitary homeobox 1 gene expression in the progression and prognosis of cutaneous malignant melanoma.

PubMed

Barut, Figen; Udul, Perihan; Kokturk, Furuzan; Kandemir, Nilufer Onak; Keser, Sevinc Hallac; Ozdamar, Sukru Oguz

2016-10-01

The evidence that PITX1 (pituitary homeobox 1) is a significant tumor suppressor in human cancer remains largely circumstantial, but it clearly warrants further study as little is known about the tumor-inhibitory roles of PITX1 in cutaneous malignant melanoma. The aims of this study were to investigate PITX1 gene expression in patients with cutaneous malignant melanoma and to evaluate its potential relevance to clinicopathological characteristics and tumor cell proliferation. Clinicopathological findings of patients with cutaneous malignant melanoma were analyzed retrospectively. PITX1 and Ki-67 expression were detected by immunohistochemistry in malignant melanoma and healthy tissue samples from each patient. Labeling indices were calculated based on PITX1 gene and Ki-67 expression. The correlation between PITX1and Ki-67 expressions was analyzed in cutaneous malignant melanoma cases. The relationship between PITX1 expression intensity and clinicopathological characteristics was also analyzed. PITX1 expression was observed in all (100%) normal healthy skin tissue samples. In addition, PITX1 expression was found in 56 (80%) and was absent in 14 (20%) of the 70 cutaneous malignant melanoma cases. Ki-67 positive expression was only detected in the 14 (20%) PITX1-negative cases. PITX1-positive tumor cells were observed on the surface, but Ki-67 positive tumor cells were observed in deeper zones of the tumor nests. PITX1 expression was downregulated in human cutaneous malignant melanoma lesions compared with healthy skin tissue, but Ki-67 expression was upregulated in concordance with the progression of cutaneous malignant melanoma. PITX1 expression may be involved in tumor progression and is a potential tumor suppressor gene and prognostic marker for cutaneous malignant melanoma. Copyright © 2016. Published by Elsevier Taiwan.

Association between proto-oncogene mutations and clinicopathologic characteristics and overall survival in colorectal cancer in East Azerbaijan, Iran

PubMed Central

Dolatkhah, Roya; Somi, Mohammad Hossein; Asvadi Kermani, Iraj; Bonyadi, Morteza; Sepehri, Bita; Boostani, Kamal; Azadbakht, Saleh; Fotouhi, Nikou; Farassati, Faris; Dastgiri, Saeed

2016-01-01

Background Colorectal cancer (CRC) is the third-most common cancer in Iran. The increasing incidence of CRC in the past three decades has made it a major public health burden in the country. This study aimed to determine any relationship of specific mutations in CRCs with clinicopathologic aspects and outcome of patients. Materials and methods This study was conducted on 100 CRC patients by the case-only method. Polymerase chain-reaction products were analyzed by Sanger sequencing, and sequence results were compared with the significant KRAS and BRAF gene mutations in the My Cancer Genome database. Logistic regression models were used to detect associations of clinicopathologic characteristics with each of the mutations. Kaplan–Meier and Cox regression models were constructed to estimate overall survival in patients. Results A total of 26 subjects (26%) had heterozygote-mutant KRAS, and mutations were not detected in the amplified exon of BRAF in both tumor and normal tissues of the 100 CRCs. Rectal tumors had 1.53-fold higher likelihood of KRAS mutations than colon tumors, and men had 1.37-fold higher odds than women. The presence of metastasis increased the likelihood of KRAS mutations 2.36-fold over those with nonmetastatic CRCs. Compared to patients with KRAS wild-type cancers, those with KRAS mutations had significantly higher mortality (hazard ratio 3.74, 95% confidence interval 1.44–9.68; log-rank P=0.003). Conclusion Better understanding of the causality of CRC can be established by combining epidemiology and research on molecular mechanisms of the disease. PMID:27994469

A Comparative Clinicopathologic Study of Collagenous Gastritis in Children and Adults: The Same Disorder With Associated Immune-mediated Diseases.

PubMed

Ma, Changqing; Park, Jason Y; Montgomery, Elizabeth A; Arnold, Christina A; McDonald, Oliver G; Liu, Ta-Chiang; Salaria, Safia N; Limketkai, Berkeley N; McGrath, Kevin M; Musahl, Tina; Singhi, Aatur D

2015-06-01

Collagenous gastritis is a rare condition characterized by surface epithelial damage, subepithelial collagen deposition, and a lamina propria inflammatory infiltrate. Previous studies have proposed 2 clinicopathologic subtypes: (1) children (18 y of age or younger) presenting with severe anemia, nodular gastric mucosa, and isolated gastric disease; and (2) adults with chronic watery diarrhea that is associated with diffuse collagenous involvement of the gastrointestinal tract. However, notable exceptions exist. In fact, broad variability in clinical presentation, etiology, treatment and disease course has been reported. To better define the clinicopathologic features of collagenous gastritis, we have collected 10 pediatric and 21 adult cases and describe their clinical, endoscopic, pathologic, and follow-up findings. Both children and adults presented with similar clinical symptoms such as anemia (50%, 35%, respectively), epigastric/abdominal pain (50%, 45%), and diarrhea (40%, 55%). Concomitant immune disorders were identified in 2 (20%) children and 3 (14%) adults. Further, 7 of 17 (41%) adults were taking medications associated with other immune-related gastrointestinal diseases including olmesartan and antidepressants. Histologically, there were no differences between children and adults with collagenous gastritis in the location of gastric involvement, mean collagenous layer thickness, and prominence of eosinophils (P>0.05). Extragastric collagenous involvement was also seen with comparable frequencies in each cohort (44%, 59%). Follow-up information was available for 22 of 31 (71%) patients and ranged from 2 to 122 months (mean, 33.6 mo). Despite medical management in most cases, persistence of symptoms or collagenous gastritis on subsequent biopsies was seen in 100% of children and 82% of adults. Of note, treatment for 1 adult patient involved cessation of olmesartan resulting in resolution of both symptoms and subepithelial collagen deposition on subsequent biopsies. Contrary to prior reports, no clinicopathologic differences were identified among pediatric and adult patients with collagenous gastritis. Whereas collagenous gastritis remains an enigmatic condition, our findings suggest that immune abnormalities and medications, such as olmesartan, may be possible triggers. However, current treatment options have had limited success and, thus, highlight the need for improved therapeutic regimens.

Comparative Study of Hand-Sutured versus Circular Stapled Anastomosis for Gastrojejunostomy in Laparoscopy Assisted Distal Gastrectomy

PubMed Central

Seo, Su Hyun; Kim, Min Chan; Choi, Hong Jo; Jung, Ghap Joong

2012-01-01

Purpose Mechanical stapler is regarded as a good alternative to the hand sewing technique, when used in gastric reconstruction. The circular stapling method has been widely applied to gastrectomy (open orlaparoscopic), for gastric cancer. We illustrated and compared the hand-sutured method to the circular stapling method, for Billroth-II, in patients who underwent laparoscopy assisted distal gastrectomy for gastric cancer. Materials and Methods Between April 2009 and May 2011, 60 patients who underwent laparoscopy assisted distal gastrectomy, with Billroth-II, were enrolled. Hand-sutured Billroth-II was performed in 40 patients (manual group) and circular stapler Billroth-II was performed in 20 patients (stapler group). Clinicopathological features and post-operative outcomes were evaluated and compared between the two groups. Results Nosignificant differences were observed in clinicopathologic parameters and post-operative outcomes, except in the operation times. Operation times and anastomosis times were significantly shorter in the stapler group (P=0.004 and P<0.001). Conclusions Compared to the hand-sutured method, the circular stapling method can be applied safely and more efficiently, when performing Billroth-II anastomosis, after laparoscopy assisted distal gastrectomy in patients with gastric cancer. PMID:22792525

Are clinicopathological features of colorectal cancers with methylation in half of CpG island methylator phenotype panel markers different from those of CpG island methylator phenotype-high colorectal cancers?

PubMed

Bae, Jeong Mo; Rhee, Ye-Young; Kim, Kyung Ju; Wen, Xianyu; Song, Young Seok; Cho, Nam-Yun; Kim, Jung Ho; Kang, Gyeong Hoon

2016-01-01

CpG island methylator phenotype (CIMP)-high (CIMP-H) colorectal cancer (CRC) is defined when a tumor shows methylation at greater than or equal to 60% of CIMP panel markers. Although CRCs with methylation at 50% of panel markers are classified as CIMP-low/CIMP-0 tumors, little is known regarding the clinicopathological and molecular features of CRCs with methylation at 4/8 panel markers (4/8 methylated markers) and whether they are akin to CIMP-H or CIMP-low/CIMP-0 CRCs in terms of their clinicopathological or molecular features. A total of 1164 cases of surgically resected CRC were analyzed for their methylation status in 8 CIMP panel markers, and the frequencies of various clinicopathological and molecular features were compared between CRCs with 0/8, 1/8 to 3/8, 4/8, and 5/8 to 8/8 methylated markers. CRCs with 4/8 methylated markers were closer to CRCs with 5/8 to 8/8 methylated markers in terms of sex distribution, mucin production, serration, nodal metastasis, CK7 expression, CK20 loss, and CDX2 loss frequencies and overall survival rate. CRCs with methylation at 4/8 markers were closer to CRCs with 1/8 to 3/8 methylated markers in terms of less frequent right colon location and poor differentiation. CRCs with 4/8 methylated markers showed the shortest overall survival time compared with CRCs with 0/8, 1/8 to 3/8, 4/8, or 5/8 to 8/8 methylated markers. In terms of clinicopathological and molecular features, CRCs with 4/8 methylated markers appeared to be closer to CIMP-H than to CIMP-low/CIMP-0 and would thus be better classified as CIMP-H if the CRCs require classification into either CIMP-H or CIMP-low/CIMP-0. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinicopathological and Prognostic Analysis of Primary Gastrointestinal Stromal Tumor Presenting with Gastrointestinal Bleeding: a 10-Year Retrospective Study.

PubMed

Yin, Zhijie; Gao, Jinbo; Liu, Weizhen; Huang, Cheng; Shuai, Xiaoming; Wang, Guobin; Tao, Kaixiong; Zhang, Peng

2017-05-01

The objectives of this paper were to investigate the clinicopathological characteristics and prognostic factors of GI-bleeding GIST patients and explore whether GI bleeding is a risk factor for GIST relapse. Primary GIST patients with initial symptoms of GI bleeding or no GI bleeding were retrospectively studied. Up to 178 GI-bleeding GIST patients including 108 (60.7%) males and 70 (39.3%) females were evaluated for the clinicopathological characteristics. The stomach, small bowel, and colorectum were the tumor sites in 82 (46.1%), 85 (47.8%), and 11 (6.2%) patients. Of the 178 patients, 163 GI-bleeding patients had follow-up while another 363 patients from the total population presented without GI bleeding were followed up. Up to 526 patients who received postoperative follow-up were included in the survival analysis. Compared with the 363 non-GI-bleeding patients, GI-bleeding patients developed smaller tumors (P = 0.015) and had a longer relapse-free survival (RFS; P = 0.014). For the 163 GI-bleeding patients, a Cox regression analysis showed that the mitotic count and the platelet-lymphocyte ratio before surgery were independent prognostic predictors for poor outcome regarding RFS. For all 526 patients, a Cox regression analysis indicated that tumor location, mitotic index, platelet-lymphocyte ratio, and GI bleeding were independent prognosis predictors. Compared to non-GI-bleeding GIST patients, patients with GI bleeding were more likely to be male and to have more small intestine GISTs, smaller tumors, and a longer RFS. For GI-bleeding patients, mitotic count and platelet-lymphocyte ratio were independent prognostic indicators. GI bleeding served as a surrogate for smaller GIST and was a protective factor for GIST recurrence.

Intraductal oncocytic papillary neoplasms of the pancreas and bile ducts: a description of five new cases and review based on a systematic survey of the literature.

PubMed

Liszka, Lukasz; Pajak, Jacek; Zielińska-Pajak, Ewa; Krzych, Lukasz; Gołka, Dariusz; Mrowiec, Sławomir; Lampe, Paweł

2010-05-01

Intraductal oncocytic papillary neoplasms (IOPN) are rare tumors of the pancreatic and biliary ductal system. It is not absolutely clear if the molecular and clinicopathologic characteristics of IOPN differ significantly from other related lesions, namely intraductal papillary mucinous neoplasms (IPMN). Therefore it is not clear if it is reasonable to consider IOPN as a separate diagnostic and clinical entity. In order to describe the clinicopathologic characteristics of IOPN and to compare them with the IPMN profile, we performed a systematic review of the literature and additionally studied five previously unreported IOPN cases. IOPN differ from IPMN by lack of K-ras gene mutations in all studied cases. Several differences in the clinical and biological profile between IOPN and IPMN exist, but they are of quantitative rather than of qualitative nature. Additionally, pancreaticobiliary or gastric-foveolar IPMN components may coexist with IOPN component within a single lesion, which suggests at least a partial relation of the pathogenetic pathways of IPMN and IOPN. Importantly, the pathogenesis of accumulation of mitochondria and oxyphilic appearance of IOPN remains unknown. At present, there are no reliable criteria other than histopathological picture and K-ras gene status to differentiate IOPN from IPMN. In particular, no clear differences in optimal treatment options and prognosis between these tumors are known. Further studies are needed to clarify the biology of IOPN and to establish their position in clinicopathologic classifications of pancreatic tumors.

WhatsApp: a telemedicine platform for facilitating remote oral medicine consultation and improving clinical examinations.

PubMed

Petruzzi, Massimo; De Benedittis, Michele

2016-03-01

Increased use of smartphone and related software applications has created a new era in clinical data exchange among patients and clinicians. This study describes use of the smartphone-based application WhatsApp to share clinical oral medicine information. Clinical images and related questions were submitted by general dentists, physicians, dental hygienists, and patients to the authors via WhatsApp. For each submission, a clinical impression was made and categorized as traumatic, infective, neoplastic, autoimmune, or unclassified. Submissions were summarized by sender type, number of photographs per sender, and category of question. Patients were invited to undergo a clinical examination with biopsy, when indicated. The telemedicine impression was compared to the clinicopathologic diagnosis. Three hundred and thirty-nine images were received for 96 patients; 92 (95.8%) patients underwent clinicopathologic examination, and 45 (49%) received a biopsy. General dentists (62%) and dental hygienists (26%) were the most frequent senders. The most common question was related to diagnosis (56%). The telemedicine impression agreed with the clinicopathologic assessment for 82% of cases. Telemedicine applications, such as WhatsApp, can support communication about oral conditions among clinicians and patients. Telemedicine consultation reduced geographic barriers to initial clinical consultation and encouraged the significant majority of patients to pursue expert clinical examination. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinicopathological importance of anterior prostate cancer in Japanese Men.

PubMed

Sato, Shun; Takahashi, Hiroyuki; Kimura, Takahiro; Egawa, Shin; Furusato, Bungo; Ikegami, Masahiro

2017-03-01

Prostate cancer of transition zone origin or anterior location has been recognized as infrequent, smaller in size and indolent, whereas, our previous report showed that transition zone/anterior cancer was frequently experienced in Japanese men. The current study was conducted to show clinicopathological characteristics of transition zone/anterior cancer. A total of 201 radical prostatectomy specimens were categorized as cancer of anterior or posterior prostate where more than two thirds of the tumor existed in the specific area. Clinicopathological characteristics including Gleason score, pathological stage, lymph node metastasis, extraprostatic extension, surgical incision into the prostate (shown as pT2+), and surgical margin status were compared between anterior and posterior cases. Cases were divided as 83, 73, and 45 of anterior, posterior cancer, and no dominance, respectively. Anterior cancers included significant numbers of high grade tumors (13/83 cases: 15.7%), which was less than posterior cancers (28.8%: 21/73). The cases in pT2+ were significantly more frequent in anterior cases than posterior ones (22.9% vs. 4.1%). No seminal vesicle invasion was shown in anterior cases. Thus, although anterior cancers are less aggressive than posterior cancers, a significant numbers of clinically important cancers were located in the anterior portion in Japanese men. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Clinicopathological Study of 30 Cases of Peripheral T-cell Lymphoma with Hodgkin and Reed-Sternberg-like B-cells from Japan.

PubMed

Eladl, Ahmed E; Satou, Akira; Elsayed, Ahmed Ali; Suzuki, Yuka; Kato, Seiichi; Asano, Naoko; Nakamura, Shigeo

2017-04-01

The presence of Hodgkin and Reed-Sternberg (HRS)-like B-cells in peripheral T-cell lymphoma (PTCL) is rare and its clinicopathological features still remain unclear. Here, we describe 30 cases of PTCL with HRS-like B-cells from Japan. Twenty-three cases (77%) presented evidence of follicular T-helper phenotype (TFH) derivation: 12 were angioimmunoblastic T-cell lymphoma and 11 PTCL with TFH phenotype (PTCL-TFH). The remaining seven cases were diagnosed as PTCL, not otherwise specified (PTCL-NOS). Epstein-Barr virus (EBV) reactivation was detected in 25 cases (83%), but HRS-like B-cells were EBER in only 20 cases (67%). The median age at diagnosis was 77 years (range, 39-91 y), including 24 patients (80%) were older than 60 years of age. Most of the patients presented at an advanced clinical stage and were associated with higher risk according to the International Prognostic Index. The 3-year overall and progression-free survival rates were 44% and 27%, respectively. No significant clinicopathological differences were detected between PTCL-TFH, PTCL-NOS and the angioimmunoblastic cases. Cases with EBER HRS-like B-cells were associated with inferior overall and progression-free survival compared to those with EBER HRS-like B-cells, but the difference was not significant. In conclusion, HRS-like B-cells were found in a subset of T-cell lymphomas, especially in association with the TFH phenotype and EBV reactivation. These cells have a tendency to affect elderly patients and to be associated with advanced clinical stages and dismal prognosis. The EBV status of HRS-like B-cells does not seem to affect the clinicopathological features of this group of PTCLs.

Differential clinicopathological features in microsatellite instability-positive colorectal cancers depending on CIMP status.

PubMed

Bae, Jeong Mo; Kim, Mi Jung; Kim, Jung Ho; Koh, Jae Moon; Cho, Nam-Yun; Kim, Tae-You; Kang, Gyeong Hoon

2011-07-01

Microsatellite instability-positive (MSI+) colorectal cancers (CRCs) are divided into CpG island methylator phenotype-positive (CIMP+) and CpG island methylator phenotype-negative (CIMP-) tumors. The repertoire of inactivated genes in CIMP+/MSI+ CRCs overlaps with but is likely to differ from that of CIMP-/MSI+ CRCs. Because epigenotypic differences are likely to be manifested as phenotypic differences, CIMP+/MSI+ CRCs are expected to differ from CIMP-/MSI+ CRCs in some clinicopathological features. This study aimed to characterize both common and different features between the two subtypes. A total of 72 MSI+ CRCs were analyzed for their methylation status in eight CIMP panel markers using MethyLight assay. CIMP+/MSI+ and CIMP-/MSI+ CRCs were compared regarding clinicopathologic features and mutation in KRAS/BRAF. An independent set of MSI+ CRCs (n = 97) was analyzed for their relationship of CIMP+ status with clinical outcome. Eighteen cases (25%) were CIMP+, and this CIMP+ subtype was highly correlated with older age (P < 0.001). Polypoid gross appearance without ulceration was observed only in CIMP-/MSI+ CRCs (18.5%, P = 0.057). CIMP+/MSI+ CRCs were closely associated with poor differentiation, medullary appearance, signet ring cell appearance, and acinar-form appearance, whereas the CIMP-/MSI+ subtype was closely associated with intraglandular eosinophilic mucin and stratified nuclei (all P values <0.05). Patients with CIMP+/MSI+ CRCs showed worse overall survival than patients with CIMP-/MSI+ CRCs. Our results demonstrate heterogeneity in the clinicopathological features of MSI+ CRCs depending on CIMP status. The observation that CIMP+ and CIMP- subtypes showed different clinical behaviors may provide a clue for establishing subtype-specific therapeutic strategies for these two subtypes.

Clinicopathological and prognostic significance of MUC13 and AGR2 expression in intraductal papillary mucinous neoplasms of the pancreas.

PubMed

Mito, Kumiko; Saito, Michihiro; Morita, Kohei; Maetani, Iruru; Sata, Naohiro; Mieno, Makiko; Fukushima, Noriyoshi

2018-06-01

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a primary pancreatic ductal epithelial neoplasm with the potential to develop into an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic and prognostic significance of four potential biomarkers for the preoperative evaluation of patients with IPMN. Clinicopathologic materials from 104 patients with IPMN who underwent surgical resection at Jichi Medical University Hospital were analyzed. IPMNs (110 lesions in total) were histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n = 26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and FXYD3, which were previously reported to be overexpressed in pancreatic ductal adenocarcinoma. The expression of MUC13 was more common in Group 3 compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor location, histological subtype, lymphatic or vascular invasion, or neural invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show an association with tumor recurrence and poorly differentiated histology of invasive carcinoma; however, this association was not statistically significant. The expressions of FUT8 and FXYD3were not associated with the clinicopathological features of IPMNs. The results suggest that MUC13 overexpression and loss of expression of AGR2 may predict the progression of IPMN and an unfavorable prognosis in patients with IPMN. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Esophageal foreign body ingestion in adults on weekdays and holidays

PubMed Central

Zhong, Qian; Jiang, Ruiwei; Zheng, Xi; Xu, Guifang; Fan, Xiuqin; Xu, Yuanyuan; Liu, Fei; Peng, Chunyan; Ren, Wei; Wang, Lei

2017-01-01

Abstract The purpose of this study is to compare the clinicopathological characteristics and outcomes of esophageal foreign body (FB) ingestion in adults between weekdays and holidays. This is a retrospective study including 1058 patients with esophageal FB ingestion from 2012 to 2016. Patient characteristics, the types and locations of FB, and clinical outcomes were compared between patients on weekdays and holidays. Furthermore, independent risk factors of complication on weekdays and holidays respectively were evaluated. The locations of FB, underlying diseases, and complications significantly differed between weekdays and holidays groups, while no difference was found in the types of FB. Patients got higher percentage of erosion complication on holidays than that on weekdays (60.8% vs 47.6%, P < .0001). Multivariate logistic regression analysis revealed that jujube shell was a significant predictor of complication on weekdays (P < .001). However, complication was significantly associated with nonfood bolus FB ingestion on holidays (P < .001). Our data suggest that there were different clinicopathological characteristics of FB ingestion between weekdays and holidays, and more patients got complications on holidays. On holidays, a latex protector hood or an overtube should be applied to patients who swallowed nonfood bolus in order to reduce esophageal mucosal damage. PMID:29069038

Over-expression of IQGAP1 indicates poor prognosis in head and neck squamous cell carcinoma.

PubMed

Wu, Cong-Cong; Li, Hao; Xiao, Yao; Yang, Lei-Lei; Chen, Lei; Deng, Wei-Wei; Wu, Lei; Zhang, Wen-Feng; Sun, Zhi-Jun

2018-05-30

IQ-domain GTPase-activating protein 1 (IQGAP1) is associated with the development and progression of many human cancers. We aimed to investigate the expression and clinicopathological significances of IQGAP1 in head and neck squamous cell carcinoma (HNSCC). In this study, immunohistochemical staining of IQGAP1, co-inhibitory immune checkpoint molecules and macrophage markers were performed in human HNSCC samples to analyze the expression and correlation with clinicopathological characteristics. Immunoreactivity of IQGAP1 was also detected in immunocompetent mouse HNSCC tissue. We found that IQGAP1 expression level was significantly increased in human HNSCC compared with dysplasia and normal mucosa, and the expression of IQGAP1 in HNSCC was positively associated with advanced lymph node status. Besides, our data indicated that patients with higher IQGAP1 expression exhibited poor overall survival compared with patients with lower IQGAP1 expression. Furthermore, this study demonstrated that IQGAP1 expression was positively associated with TIM3, Galectin-9 (TIM3 ligand), B7H4, macrophage markers CD68 and CD163. In conclusion, these findings suggest that over-expression of IQGAP1 in human HNSCC may indicate poor prognosis.

Prognostic and clinicopathological significance of platelet to lymphocyte ratio in esophageal cancer: a meta-analysis.

PubMed

Deng, Juhong; Zhang, Peng; Sun, Yue; Peng, Ping; Huang, Yu

2018-03-01

The prognostic and clinicopathological significance of the platelet to lymphocyte ratio (PLR) has been studied in various cancers. However, studies examining the role of PLR in esophageal cancer have not yielded consistent results. The purpose of this meta-analysis was to study the prognostic and clinicopathological significance of PLR in esophageal cancer patients. We performed a literature search in three major databases: PubMed, Web of Science and Embase (up until May 1, 2017). The clinicopathologic significance of PLR and its prognostic significance were analyzed. Our meta-analysis consisted of 13 studies with 4,621 patients. The pooled hazard ratios (HRs) showed that a high PLR was associated with poor survival of esophageal cancer [HR =1.283; 95% confidence interval (CI): 1.173-1.404; P<0.001]. Subgroup analysis revealed that elevated PLR was associated with poor survival in esophageal squamous cell carcinoma (HR =1.281; 95% CI: 1.098-1.493; P=0.002). The pooled odds ratio (OR) indicated that high PLR was also associated with the depth of tumor invasion (OR =1.543, 95% CI: 1.269-1.876, P<0.001), lymph node metastasis (OR =1.427, 95% CI: 1.195-1.705, P<0.001), tumor length (OR =1.81, 95% CI: 1.331-2.461, P<0.001), and Tumor stage (OR =1.459, 95% CI: 1.235-1.724, P<0.001). Our results demonstrate that elevated PLR was significantly associated with poor prognosis of esophageal cancer. Furthermore, the high PLR might predict worse clinicopathological features of esophageal cancer patients.

Clinicopathological Features of Cervical Esophageal Cancer: Retrospective Analysis of 63 Consecutive Patients Who Underwent Surgical Resection.

PubMed

Saeki, Hiroshi; Tsutsumi, Satoshi; Yukaya, Takafumi; Tajiri, Hirotada; Tsutsumi, Ryosuke; Nishimura, Sho; Nakaji, Yu; Kudou, Kensuke; Akiyama, Shingo; Kasagi, Yuta; Nakashima, Yuichiro; Sugiyama, Masahiko; Sonoda, Hideto; Ohgaki, Kippei; Oki, Eiji; Yasumatsu, Ryuji; Nakashima, Torahiko; Morita, Masaru; Maehara, Yoshihiko

2017-01-01

The objectives of this retrospective study were to elucidate the clinicopathological features and recent surgical results of cervical esophageal cancer. Cervical esophageal cancer has been reported to have a dismal prognosis. Accurate knowledge of the clinical characteristics of cervical esophageal cancer is warranted to establish appropriate therapeutic strategies. The clinicopathological features and treatment results of 63 consecutive patients with cervical esophageal cancer (Ce group) who underwent surgical resection from 1980 to 2013 were analyzed and compared with 977 patients with thoracic or abdominal esophageal cancer (T/A group) who underwent surgical resection during that time. Among the patients who received curative resection, the 5-year overall and disease-specific survival rates of the Ce patients were significantly better than those of the T/A patients (overall: 77.3% vs 46.5%, respectively, P = 0.0067; disease-specific: 81.9% vs 55.8%, respectively, P = 0.0135). Although total pharyngo-laryngo-esophagectomy procedures were less frequently performed in the recent period, the rate of curative surgical procedures was markedly higher in the recent period (2000-1013) than that in the early period (1980-1999) (44.4% vs 88.9%, P = 0.0001). The 5-year overall survival rate in the recent period (71.5%) was significantly better than that in the early period (40.7%, P = 0.0342). Curative resection for cervical esophageal cancer contributes to favorable outcomes compared with other esophageal cancers. Recent surgical results for cervical esophageal cancer have improved, and include an increased rate of curative resection and decreased rate of extensive surgery.

Clinicopathological characteristic and clinical handling of the patients with 2 cm or less gastric GISTs.

PubMed

Kataoka, Mikinori; Kawai, Takashi; Ikemiyagi, Hidekazu; Fujii, Takashi; Fukuzawa, Mari; Fukuzawa, Masakatsu; Kubota, Keisuke; Yoshida, Masashi; Suzuki, Shinji; Kitajima, Masaki

2013-01-01

We previously reported that safety and efficacy of mucosal cutting biopsy for diagnosing included 2 cm or less gastric GISTs. However, there have been no reports stating the clinicopathological characteristic and clinical handling of the patients with 2 cm or less gastric GISTs. The aim of our study is to investigate the clinicopathological characteristic and clinical handling of the patients with 2 cm or less gastric GISTs. The 19 patients diagnosed with GIST by mucosal cutting biopsy were divided into 2 groups: Group I; subjects were GISTs with 2 cm or less, Group II; subjects were GISTs >2 cm. We compared the 2 groups in terms of mean age, tumor size, tumor site, histopathological risk grade. In cases that underwent surgery with a diagnosis of GIST, we compared the pre- and postoperative histopathological diagnosis, and the histopathlogical risk grade within each group. The mean age and tumor size were significantly higher in Group I than in Group II. Meanwhile, there were no significant differences between the 2 groups, sex ratio, tumor site. All lesions were at histopathological risk grade at very low risk and low risk respectively. In 17 patients with GIST who underwent surgery, the histopathological diagnoses, immunostaining were in agreement with those from the mucosal cutting biopsy specimens in all cases, but mitotic count of one patient was not in agreement in group II. The 2 cm or less gastric GISTs diagnosed with histpathlogical very low risk can be considered acceptable to follow-up.

Expression of microRNA 638 and sex-determining region Y-box 2 in hepatocellular carcinoma: Association between clinicopathological features and prognosis.

PubMed

Ye, Weikang; Li, Jieke; Fang, Guan; Cai, Xiupeng; Zhang, Yan; Zhou, Chaojun; Chen, Lei; Yang, Wenjun

2018-05-01

The aim of the present study was to determine the expression profile of microRNA 638 (miR-638) and sex-determining region Y-box 2 (SOX2) in hepatocellular carcinoma (HCC), and to investigate their association with clinicopathological features and survival. Reverse transcription-quantitative polymerase chain reaction analysis was used to investigate miR-638 and SOX2 expression in 78 patients with HCC. Western blot and immunohistochemical analyses were performed in order to determine SOX2 protein expression in HCC samples. Combined with the clinical postoperative follow-up data, the expression of miR-638 and SOX2 and the association between this and the prognostic values of patients with HCC were statistically analyzed. The results of the present study confirmed that miR-638 expression in tumor tissues was significantly downregulated (P<0.001), while SOX2 expression was significantly increased, compared with healthy control tissues (P<0.05). In addition, a significant inverse correlation between miR-638 and SOX2 expression was also observed in the HCC tissues (r=-0.675; P<0.05). Clinicopathological correlation analysis demonstrated that reduced miR-638 and elevated SOX2 expression was significantly associated with the Tumor-Node-Metastasis stage and portal vascular invasion (P<0.05). However, no significant differences were observed in other clinicopathological features, including age, sex, tumor size, tumor differentiation and hepatitis status (P>0.05). Notably, follow-up analysis revealed that patients with HCC with low miR-638 expression and high SOX2 expression tended to have a significantly shorter postoperative survival time (P<0.001). It was concluded that miR-638 may serve a vital role in the occurrence and progression of HCC by regulating SOX2 expression and thus, that miR-638 and SOX2 may be critical as novel diagnostic and prognostic biomarkers for HCC.

Clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma: a meta-analysis.

PubMed

Qu, Hai-Xia; Zhao, Li-Ping; Zhan, Shu-Hui; Geng, Chang-Xin; Xu, Lin; Xin, Yong-Ning; Jiang, Xiang-Jun

2016-11-01

The clinicopathological and prognostic significance of programmed cell death ligand 1 (PD-L1) expression in patients with esophageal squamous cell carcinoma (ESCC) remains controversial. To investigate this question, we conducted a meta-analysis. A comprehensive literature search of electronic databases (up to July 10, 2016) was performed for relevant studies using multiple search strategies. Correlation between PD-L1 expression and clinicopathological features/overall survival (OS) was analyzed. A total of 1,350 ESCC patients from eight studies were included. The pooled odds ratios (ORs) indicated that none of the clinicopathological characteristics was correlated with PD-L1 expression, including gender [OR =0.84; 95% confidence interval (CI): 0.59-1.18; P=0.31], histological differentiation (OR =1.33; 95% CI: 0.95-1.85; P=0.09), tumor depth (OR =0.66; 95% CI: 0.33-1.35; P=0.26), status of lymph node metastasis (OR =0.67; 95% CI: 0.30-1.52; P=0.34), distal metastasis (OR =0.66; 95% CI: 0.40-1.09; P=0.10) and tumor node metastasis (TNM) stage (OR =0.93; 95% CI: 0.49-1.75; P=0.82). The combined hazard ratio (HR) for OS showed a trend that overexpression of PD-L1 might be associated with the survival outcome of ESCC, though the difference was not statistically significant (HR =1.65; 95% CI 0.95-2.85; P=0.07). Based on the published studies, PD-L1 overexpression in ESCC was not associated with common clinicopathological characteristics. PD-L1 might be a poor prognostic biomarker for ESCC. Further large-scale research should be performed to reveal the precise clinicopathological and prognostic significance of PD-L1 in ESCC by unified testing standard.

Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal cancer.

PubMed

Wei, Xiao-Li; Wang, De-Shen; Xi, Shao-Yan; Wu, Wen-Jing; Chen, Dong-Liang; Zeng, Zhao-Lei; Wang, Rui-Yu; Huang, Ya-Xin; Jin, Ying; Wang, Feng; Qiu, Miao-Zhen; Luo, Hui-Yan; Zhang, Dong-Sheng; Xu, Rui-Hua

2014-12-28

To explore the association between AT-rich interactive domain 1A (ARID1A) protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer. We retrospectively collected clinicopathologic data and archived paraffin-embedded primary colorectal cancer samples from 209 patients, including 111 patients with colon cancer and 98 patients with rectal cancer. The tumor stage ranged from stage I to stage IV according to the 7(th) edition of the American Joint Committee on Cancer tumor-node-metastasis (TNM) staging system. All patients underwent resection of primary colorectal tumors. The expression of ARID1A protein in primary colorectal cancer tissues was examined by immunohistochemical staining. The clinicopathologic association and survival relevance of ARID1A protein loss in colorectal cancer were analyzed. ARID1A loss by immunohistochemistry was not rare in primary colorectal cancer tumors (25.8%). There were 7.4%, 24.1%, 22.2% and 46.3% of patients with ARID1A loss staged at TNM stage I, II, III and IV, respectively, compared with 20.0%, 22.6%, 27.7% and 29.7% of patients without ARID1A loss staged at TNM stage I, II, III and IV, respectively. In patients with ARID1A loss, the distant metastasis rate was 46.3%. However, only 29.7% of patients without ARID1A loss were found to have distant metastasis. In terms of pathologic differentiation, there were 25.9%, 66.7% and 7.4% with poorly, moderately and well differentiated tumors in patients with ARID1A loss, and 14.2%, 72.3% and 13.5% with poorly, moderately and well differentiated tumors in patients without ARID1A loss, respectively. ARID1A loss was associated with late TNM stage (P = 0.020), distant metastasis (P = 0.026), and poor pathological classification (P = 0.035). However, patients with positive ARID1A had worse overall survival compared to those with negative ARID1A in stage IV colorectal cancer (HR = 2.49, 95%CI: 1.13-5.51). ARID1A protein loss is associated with clinicopathologic characteristics in colorectal cancer patients and with survival in stage IV patients.

Esophageal foreign body ingestion in adults on weekdays and holidays: A retrospective study of 1058 patients.

PubMed

Zhong, Qian; Jiang, Ruiwei; Zheng, Xi; Xu, Guifang; Fan, Xiuqin; Xu, Yuanyuan; Liu, Fei; Peng, Chunyan; Ren, Wei; Wang, Lei

2017-10-01

The purpose of this study is to compare the clinicopathological characteristics and outcomes of esophageal foreign body (FB) ingestion in adults between weekdays and holidays. This is a retrospective study including 1058 patients with esophageal FB ingestion from 2012 to 2016. Patient characteristics, the types and locations of FB, and clinical outcomes were compared between patients on weekdays and holidays. Furthermore, independent risk factors of complication on weekdays and holidays respectively were evaluated. The locations of FB, underlying diseases, and complications significantly differed between weekdays and holidays groups, while no difference was found in the types of FB. Patients got higher percentage of erosion complication on holidays than that on weekdays (60.8% vs 47.6%, P < .0001). Multivariate logistic regression analysis revealed that jujube shell was a significant predictor of complication on weekdays (P < .001). However, complication was significantly associated with nonfood bolus FB ingestion on holidays (P < .001). Our data suggest that there were different clinicopathological characteristics of FB ingestion between weekdays and holidays, and more patients got complications on holidays. On holidays, a latex protector hood or an overtube should be applied to patients who swallowed nonfood bolus in order to reduce esophageal mucosal damage.

Clinical and clinicopathologic abnormalities in young dogs with acquired and congenital portosystemic shunts: 93 cases (2003-2008).

PubMed

Adam, Fiona H; German, Alexander J; McConnell, J Fraser; Trehy, Mary R; Whitley, Nat; Collings, Alison; Watson, Penny J; Burrow, Rachel D

2012-09-15

To determine whether clinical and clinicopathologic data could assist differentiation of congenital portosystemic shunts (CPSSs) from acquired portosystemic shunts (APSSs) in young dogs. Retrospective case series. Dogs < 30 months of age with CPSSs (n = 62) or APSSs (31). Medical records from 3 referral centers identified 31 dogs with APSSs and 62 dogs with CPSSs diagnosed from July 2003 to July 2008. Signalment, clinical signs, physical examination, and clinicopathological data were recorded, and statistical analyses were performed to determine differences between groups. Univariable analysis showed APSS patients were older, heavier, and in poorer body condition, compared with CPSS patients. In CPSS patients, diarrhea was less prevalent, and neurologic signs were more prevalent. Ascites was more prevalent in APSS (Fisher exact test; OR, 50.2; 95% confidence interval [CI], 6.2 to 409.7), with no significant difference in albumin concentration between groups. The logistic regression model used to assess clinicopathological parameters showed lower Hct (OR, 1.42 × 10(-12); 95% CI, 1.42 × 10(-17) to 4.0 × 10(-6)), higher mean corpuscular volume (OR, 1.27; 95% CI, 1.08 to 1.50), and higher alanine aminotransferase concentrations (OR, 1.005; 95% CI, 1.001 to 1.009) were more likely in APSS patients. Several clinicopathologic differences between dogs with congenital and acquired shunts were identified; however, assessed alone, these would be unlikely to enable differentiation between the 2 conditions. Awareness of the rarity of ascites in CPSS cases should prompt recognition of a likely diagnosis of APSS, allowing the veterinarian to target further diagnostics and counsel the owner appropriately.

A genomic and clinicopathological study of non-small-cell lung cancers with discordant ROS1 gene status by fluorescence in-situ hybridisation and immunohistochemical analysis.

PubMed

Zhao, Jing; Chen, Xiaotong; Zheng, Jing; Kong, Mei; Wang, Bo; Ding, Wei

2018-02-21

ROS1 immunohistochemistry (IHC) using D4D6 antibody is a useful tool for screening patients with non-small-cell lung cancer (NSCLC) who may be suitable for targeted therapy. Many studies and our data have identified cases that express the ROS1 protein strongly but are negative for ROS1 by fluorescence in-situ hybridisation (FISH). The present study investigated the driver mutation and clinicopathological characteristics of 26 discordant cases (ROS1 IHC-positive but FISH-negative) to find new clues for distinguishing real ROS1-rearranged cases. Tumours from 26 discordant cases were analysed for clinicopathological characteristics, mutations in EGFR, KRAS, ERBB2, BRAF and PIK3CA; fusions in ALK and RET; and amplifications in MET, ERBB2 and ROS1. ROS1-rearranged NSCLCs were significantly more likely to be found in younger patients and at an advanced stage; they showed cribriform features, extracellular mucus and psammoma bodies, whereas ROS1-discordant cases were found in older patients at a relatively early tumour-node-metastasis (TNM) stage and showed a lepidic growth pattern (all P < 0.001). Most ROS1-rearranged NSCLCs had no concurrent mutation, whereas 73% of discordant cases harboured genetic aberrations, including EGFR and ERBB2. Compared with general lung adenocarcinomas, ERBB-2 abnormality was disproportionately high in ROS1-discordant cases. Moreover, we optimised the scoring criteria for ROS1 IHC as 'H score > 150 and no concurrent mutations'; the specificity was then increased to 81.6%. Compared with ROS1-rearranged cases, ROS1-discordant patients showed distinct clinical and morphological features and often harboured another oncogenic driver alteration. The use of optimised screening criteria will increase the specificity of ROS1 antibody. © 2018 John Wiley & Sons Ltd.

Clinical signs and clinicopathologic abnormalities in dogs with clinical spirocercosis: 39 cases (1996-2004).

PubMed

Mylonakis, Mathios E; Rallis, Tim; Koutinas, Alexander F; Leontides, Leonidas S; Patsikas, Michail; Florou, Marianna; Papadopoulos, Elias; Fytianou, Anna

2006-04-01

To determine clinical signs and clinicopathologic abnormalities in dogs with naturally occurring clinical spirocercosis. Retrospective case series. 39 dogs with spirocercosis. Medical records were reviewed, and information on signalment, residence (rural vs urban), owner complaints, physical examination findings, clinicopathologic abnormalities, radiographic and endoscopic findings, and concurrent systemic diseases was recorded. Hellenic hounds and mixed-breed dogs were overrepresented, compared with a group of 117 control dogs without spirocercosis that were examined because of gastrointestinal tract disease, and mean body weight of dogs with spirocercosis was significantly higher than mean body weight of control dogs. Odynophagia (34 [87%]), regurgitation (24 [62%]), and excessive salivation (14 [36%]) were the most common clinical findings. The most common radiographic abnormalities were a mass in the caudodorsal aspect of the mediastinum (15/35 [43%]) and spondylitis of the caudal thoracic vertebrae (10 [29%]). Parasitic nodules were seen during esophagoscopy in all 39 dogs. Normocytic, normochromic, nonregenerative anemia; neutrophilic leukocytosis; hyperproteinemia; and high alkaline phosphatase activity were significantly more common in dogs with spirocercosis than in a control group of 56 healthy dogs. Concurrent systemic diseases, mainly leishmaniosis, dirofilariosis, and monocytic ehrlichiosis, were documented in 14 (36%) dogs. Results suggest that clinical spirocercosis occurs more often in young-adult, large-breed dogs. Nonregenerative anemia, neutrophilic leukocytosis, hyperproteinemia, and high alkaline phosphatase activity may be useful clinicopathologic indicators of this disease.

Molecular essence and endocrine responsiveness of estrogen receptor-negative, progesterone receptor-positive, and HER2-negative breast cancer.

PubMed

Yu, Ke-Da; Jiang, Yi-Zhou; Hao, Shuang; Shao, Zhi-Ming

2015-10-05

The clinical significance of progesterone receptor (PgR) expression in estrogen receptor-negative (ER-) breast cancer is controversial. Herein, we systemically investigate the clinicopathologic features, molecular essence, and endocrine responsiveness of ER-/PgR+/HER2- phenotype. Four study cohorts were included. The first and second cohorts were from the Surveillance, Epidemiology, and End Results database (n = 67,932) and Fudan University Shanghai Cancer Center (n = 2,338), respectively, for clinicopathologic and survival analysis. The third and fourth cohorts were from two independent publicly available microarray datasets including 837 operable cases and 483 cases undergoing neoadjuvant chemotherapy, respectively, for clinicopathologic and gene-expression analysis. Characterized genes defining subgroups within the ER-/PgR+/HER2- phenotype were determined and further validated. Clinicopathologic features and survival outcomes of the ER-/PgR+ phenotype fell in between the ER+/PgR+ and ER-/PgR- phenotypes, but were more similar to ER-/PgR-. Among the ER-/PgR+ phenotype, 30% (95% confidence interval [CI] 17-42%, pooled by a fixed-effects method) were luminal-like and 59% (95% CI 45-72%, pooled by a fixed-effects method) were basal-like. We further refined the characterized genes for subtypes within the ER-/PgR+ phenotype and developed an immunohistochemistry-based method that could determine the molecular essence of ER-/PgR+ using three markers, TFF1, CK5, and EGFR. Either PAM50-defined or immunohistochemistry-defined basal-like ER-/PgR+ cases have a lower endocrine therapy sensitivity score compared with luminal-like ER-/PgR+ cases (P <0.0001 by Mann-Whitney test for each study set and P <0.0001 for pooled standardized mean difference in meta-analysis). Immunohistochemistry-defined basal-like ER-/PgR+ cases might not benefit from adjuvant endocrine therapy (log-rank P = 0.61 for sufficient versus insufficient endocrine therapy). The majority of ER-/PgR+/HER2- phenotype breast cancers are basal-like and associated with a lower endocrine therapy sensitivity score. Additional studies are needed to validate these findings.

Gliomatosis cerebri: clinicopathologic study of 33 cases and comparison of mass forming and diffuse types.

PubMed

Park, S; Suh, Y-L; Nam, D-H; Kim, S T

2009-01-01

Gliomatosis cerebri (GC) is defined as a diffuse neoplastic glial cell infiltration of the brain with the preservation of anatomical architecture and the sparing of neurons and can be classified into Type 1 (diffuse) and Type 2 (mass forming) GCs macroscopically. There is little information on subtypes of GC. The aim of this study was to evaluate the clinicopathologic findings of GCs and to compare the clinicopathologic findings between Type 1 and Type 2 GCs. A total of 33 cases of GC were obtained from pathology file of Samsung Medical Center. The diagnosis was based on magnetic resonance imaging findings and histological confirmation for all patients. Fifteen cases were classified into Type 1 and 18 were Type 2 based on the MR images. Clinical information included patients' age, sex, tumor extent, treatment modality and survival. Pathologic features included the amount of rod cells and cytologic anaplasia such as multinucleated tumor giant cells, endothelial cell proliferation, or mitosis. Immunohistochemical study was performed for GFAP, O1, Gal-C, Ki-67, and p53. Clinicopathologic comparison between subtypes and statistical analysis were performed. Median age at diagnosis was older (56 years) in Type 1 than in Type 2 (44 years). Male to female ratio was about 1.54:1. Mean survival time was shorter (21 months) in Type 2 than in Type 1 GCs (24 months) (p = 0.0447). Histologically, 33 cases of GC were classified into two histologic grades (low and high grade) by cytologic anaplasia. High-grade GC was more common in Type 2 than Type 1 (p = 0.027). Immunohistochemical results demonstrated that the infiltrating tumor cells were undifferentiated cells with astrocytic or oligodendroglial differentiation. Ki-67 labeling index was correlated with subtypes (p = 0.0096). Pathologic features were not correlated with survival. Type 1 and 2 GCs are somewhat different in clinical presentation and pathologic features. The age group, survival time, histologic grade, and Ki-67 labeling index were significantly correlated with subtypes ofGCs. Type 2 GC was correlated with poor survival but histologic grade was not.

Clinicopathologic features of patients with non-small cell lung cancer harboring the EML4-ALK fusion gene: a meta-analysis.

PubMed

Wang, Ying; Wang, Shumin; Xu, Shiguang; Qu, Jiaqi; Liu, Bo

2014-01-01

The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene. The Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted. Seventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30-0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66-3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41-0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03-0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger's test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status. This meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR.

Clinicopathologic Features of Patients with Non-Small Cell Lung Cancer Harboring the EML4-ALK Fusion Gene: A Meta-Analysis

PubMed Central

Wang, Shumin; Xu, Shiguang; Qu, Jiaqi

2014-01-01

Background The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene. Methods The Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted. Results Seventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30–0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66–3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41–0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03–0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger's test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status. Conclusion This meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR. PMID:25360721

Clinical data, clinicopathologic findings and outcome in dogs with amegakaryocytic thrombocytopenia and primary immune-mediated thrombocytopenia.

PubMed

Cooper, S A; Huang, A A; Raskin, R E; Weng, H-Y; Scott-Moncrieff, J C

2016-03-01

The aim of this study was to identify distinguishing characteristics between dogs diagnosed with amegakaryocytic thrombocytopenia and those diagnosed with presumed primary peripheral immune-mediated thrombocytopenia. Presenting clinical and clinicopathologic data and outcomes were compared between the two groups. Retrospective study performed on seven client-owned dogs diagnosed with amegakaryocytic thrombocytopenia and 34 client-owned dogs with primary peripheral immune-mediated thrombocytopenia. All dogs in the amegakaryocytic thrombocytopenia group were anaemic on presentation with a median haematocrit of 23% (range 9·4 to 36), while the primary peripheral immune-mediated thrombocytopoenia group had a median presenting haematocrit of 35% (range 10 to 53). Dogs with amegakaryocytic thrombocytopenia had a median of five (range 4 to 7) clinical signs of bleeding compared to a median of three (range 0 to 6) in the primary peripheral immune-mediated thrombocytopenia group with 86% (6 of 7) of amegakaryocytic thrombocytopenia dogs requiring a blood transfusion compared to 41% (14 of 34) of primary peripheral immune-mediated thrombocytopenia dogs. Six of the seven amegakaryocytic thrombocytopenia dogs did not survive to discharge, while only five of the 34 primary peripheral immune-mediated thrombocytopenia dogs did not survive to discharge. The clinical presentation of dogs with amegakaryocytic thrombocytopenia and primary peripheral immune-mediated thrombocytopenia is similar, but dogs with amegakaryocytic thrombocytopenia had a more severe clinical course compared to primary peripheral immune-mediated thrombocytopenia dogs. The prognosis for dogs with amegakaryocytic thrombocytopenia is poor. © 2016 British Small Animal Veterinary Association.

Clinicopathologic, Immunohistochemical, and Molecular Features of Histiocytoid Sweet Syndrome.

PubMed

Alegría-Landa, Victoria; Rodríguez-Pinilla, Socorro María; Santos-Briz, Angel; Rodríguez-Peralto, José Luis; Alegre, Victor; Cerroni, Lorenzo; Kutzner, Heinz; Requena, Luis

2017-07-01

Histiocytoid Sweet syndrome is a rare histopathologic variant of Sweet syndrome. The nature of the histiocytoid infiltrate has generated considerable controversy in the literature. The main goal of this study was to conduct a comprehensive overview of the immunohistochemical phenotype of the infiltrate in histiocytoid Sweet syndrome. We also analyze whether this variant of Sweet syndrome is more frequently associated with hematologic malignancies than classic Sweet syndrome. This is a retrospective case series study of the clinicopathologic, immunohistochemical, and molecular features of 33 patients with a clinicopathologic diagnosis of histiocytoid Sweet syndrome was conducted in the dermatology departments of 5 university hospitals and a private laboratory of dermatopathology. The clinical, histopathological, immunohistochemical, and follow-up features of 33 patients with histiocytoid Sweet syndrome were analyzed. In some cases, cytogenetic studies of the dermal infiltrate were also performed. We compare our findings with those of the literature. The dermal infiltrate from the 33 study patients (20 female; median age, 49 years; age range, 5-93 years; and 13 male; median age, 42 years; age range, 4-76 years) was mainly composed of myeloperoxidase-positive immature myelomonocytic cells with histiocytoid morphology. No cytogenetic anomalies were found in the infiltrate except in 1 case in which neoplastic cells of chronic myelogenous leukemia were intermingled with the cells of histiocytoid Sweet syndrome. Authentic histiocytes were also found in most cases, with a mature immunoprofile, but they appeared to be a minor component of the infiltrate. Histiocytoid Sweet syndrome was not more frequently related with hematologic malignancies than classic neutrophilic Sweet syndrome. The dermal infiltrate of cutaneous lesions of histiocytoid Sweet syndrome is composed mostly of immature cells of myeloid lineage. This infiltrate should not be interpreted as leukemia cutis.

Involvement of oral tissues by AL amyloidosis: a literature review and report of eight new cases.

PubMed

Matsuo, Flávia Sayuri; Barbosa de Paulo, Luiz Fernando; Servato, João Paulo Silva; de Faria, Paulo Rogério; Cardoso, Sergio Vitorino; Loyola, Adriano Mota

2016-11-01

Amyloidosis is a term used to describe a group of diseases in which there is an extracellular deposition of amorphous fibrillar proteins known as amyloid. The aim of this study was to present clinicopathological data from eight oral amyloidosis-affected patients and a deep review of the literature about the disease. A retrospective study was conducted based on the records of oral amyloidosis-affected patients diagnosed in our institution between 1978 and 2012. The clinicopathological features and immunohistochemical (IHC) staining with anti-kappa and anti-lambda light chain antibodies were carried out and analyzed. Eight patients were diagnosed with the disease; the tongue and women in their sixth decade of life were mostly affected. All lesions demonstrated apple-green birefringence and immunoreactivity for kappa-light chain, and four cases also showed lambda positivity. According to our series, four cases were diagnosed with localized amyloidosis and four with systemic amyloidosis. Prognosis for the systemic ones was gloomy, but good for the localized ones, which was characterized by a slow pattern of deposition without evolution to systemic involvement. This study reinforces our knowledge about predilections, outcomes, and the importance of making a correct and quick diagnosis of oral amyloidosis and shows the necessity of more studies detailing oral amyloidosis predilection on a global scale. The importance and utility of IHC in the typing of the biochemical nature of amyloid deposits are becoming increasingly necessary for proper management of the patient. Correct classification of the type of amyloid is important for treatment consequences. This article highlights the clinicopathological data of patients with amyloidosis affecting oral tissues and compare these new findings with other worldwide descriptions. Because of its rarity, such data are often unfamiliar to most clinicians and pathologists.

Association of CA 15-3 and CEA with clinicopathological parameters in patients with metastatic breast cancer.

PubMed

Geng, Biao; Liang, Man-Man; Ye, Xiao-Bing; Zhao, Wen-Ying

2015-01-01

The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.

Clinicopathologic Characteristics and Prognosis of Xp11.2 Translocation Renal Cell Carcinoma: Multicenter, Propensity Score Matching Analysis.

PubMed

Choo, Min Soo; Jeong, Chang Wook; Song, Cheryn; Jeon, Hwang Gyun; Seo, Seong Il; Hong, Sung Kyu; Byun, Seok-Soo; Chung, Jin Soo; Hong, Sung-Hoo; Hwang, Eu Chang; Kim, Hyeon Hoe; Kwak, Cheol

2017-10-01

We evaluated the clinicopathologic characteristics and prognosis of Xp11.2 translocation (Xp11.2t) renal cell carcinoma (RCC) from a multicenter study and compare them with clear-cell RCC using a propensity score matching analysis. Between 2004 and 2013, 8384 consecutive patients from 7 institutions who were diagnosed with RCC were reviewed, and the pathologically confirmed Xp11.2t cases were enrolled. The oncological outcomes of Xp11.2t were compared with those of clear-cell RCC by selecting matched cases using 1:3 propensity score matching methods in a precollected clear-cell RCC data set from our hospital. The patients were divided into 2 subgroups on the basis of age of onset, either before (early) or after (late) 45 years old. Xp11.2t was found in 61 cases, corresponding to 0.72% of RCC cases for the 10 years. The mean age was 38.2 ± 19.4 years, and the mean tumor size was 6.2 ± 3.9 cm. The Xp11.2t cases were at more advanced stages and showed tendencies to involve lymph nodes at diagnosis. After the matching, there were no significant differences in recurrence-free and overall survival compared with clear-cell RCC. The age of incidence for Xp11.2t had a bimodal distribution, which was most common in the 30s and smaller peak in the 60s. Xp11.2t corresponded to a significantly worse prognosis for overall survival in late onset (after 45 years) subgroup (P = .038; hazard ratio, 3.199; 95% confidence interval, 1.065-9.609). This neoplasm has more aggressive clinicopathologic features at diagnosis. In older patients with onset age > 45 years, Xp11.2t showed a significantly worse prognosis than clear-cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

[Neuroendocrine neoplasm of digestive system with different grades: a clinicopathologic and prognostic study].

PubMed

Zhang, Ming-hui; Liu, Yan-hui; Luo, Xin-lan; Lin, Xing-tao; Zhuang, Heng-guo

2012-07-01

To study the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. The clinicopathologic features of 139 cases of neuroendocrine neoplasm occurring in digestive system were retrospectively reviewed and graded according to the 2010 World Health Organization classification of tumours of the digestive system. Immunohistochemical study for synaptophysin, chromogranin A and Ki-67 was carried out. The follow-up and survival data were analysed using Kaplan-Meier method. Prognostic factors were tested by Log-rank testing and independent risk factors were analysed using Cox regression model. Amongst the 139 cases studied, there were 88 cases (63.3%) of grade 1 tumors, 9 cases (6.5%) of grade 2 tumors and 42 cases (30.2%) of grade 3 tumors. There was diffusely positive staining for synaptophysin and chromogranin A in most of the grade 1 and grade 2 tumors. The staining in grade 3 tumors however was focal (P < 0.05). The differences in tumor size, depth of invasion, presence of tumor emboli, perineural permeation, nodal involvement, distant metastasis and survival rate amongst the three groups was statistically significant (P < 0.05). There is significant difference in the clinicopathologic and prognostic features of neuroendocrine neoplasm of digestive system with different grades. It is considered as an independent prognostic factor and represents a useful tool for prognostic evaluation of such tumors, both in clinical practice and research.

Primary intrathoracic liposarcoma: a clinicopathologic study and prognostic analysis of 23 cases

PubMed Central

2014-01-01

Background Primary intrathoracic liposarcoma is an extremely rare malignancy as well as a rare histologic subtype of intrathoracic sarcoma. Relatively few reports appear in the world literatures. We explored the clinicopathologic features and prognostic factors of this tumor in this study. Methods We retrospectively analyzed the clinicopathological data of 23 patients with primary intrathoracic liposarcoma who were treated in Shanghai chest Hospital affiliated to Jiao Tong University, from January 2003 to March 2013. These patients were classified into three groups according to the distinct tumor locations, including mediastinum, pleura and lung liposarcoma. Also, these patients could be divided into four types, including well-differentiated, myxoid, dedifferentiated and pleomorphic liposarcoma. The influences of age, sex, tumor size, tumor location, tumor histologic type and therapy on the prognosis of the patients were analyzed. Results There were no significant difference for survival among distinct liposarcoma locations. However, significant difference for survival among distinct liposarcoma types were observed. Poor disease-free survival (DFS) was observed in the myxoid, pleomorphic and dedifferentiated types as compared to well-differentiated type (P = 0.038). Inferior overall-survival (OS) was observed in dedifferentiated, pleomorphic and myxoid types relative to well-differentiated type (P = 0.027). The radical surgery was a favorable prognostic factor for OS, as demonstrated by the better OS of the radical surgery group as compared to that of the non-radical surgery group ( P = 0.029). Notably, there were no significant differences for DFS and OS in other clinical parameters including tumor size, gender and age. In addition, radiotherapy and/or chemotherapy could not improve the prognosis of the patients receiving non-radical surgery or suffering from relapse. Conclusions The histological type and the radical surgery are the factors that influence the behavior and prognosis of liposarcoma. In general, radiotherapy and chemotherapy are believed to be ineffective therapeutic modalities for survival. So it is essential to completely resect the primary intrathoracic liposarcoma as radical cure of the disease. PMID:24993036

Epidemiological trends and clinicopathological features of cutaneous melanoma in sporadic and xeroderma pigmentosum Tunisian patients.

PubMed

Naouali, Chokri; Jones, Meriem; Nabouli, Imen; Jerbi, Manel; Tounsi, Haifa; Ben Rekaya, Mariem; Ben Ahmed, Melika; Bouhaouala, Balkiss; Messaoud, Olfa; Khaled, Aida; Zghal, Mohamed; Abdelhak, Sonia; Boubaker, Samir; Yacoub-Youssef, Houda

2017-01-01

Epidemiological features and trends of cutaneous melanoma (CM) in North-African populations remain unclear. Those populations are of particular interest as they belong to a mosaic of various other origins (sub-Saharan, European Ancestry, and North-African Berbers). The aim of this study is to draw epidemiological profile and clinicopathological features of CM in the Tunisian population. Incidence analyses were based on data from regional cancer registries. Clinical data were collected from dermatological departments and xeroderma pigmentosum (XP) referral centers and provided CM clinicopathological characteristics and progression. Statistical analyses were achieved using R packages and SPSS 20.0. The incidence of CM in Tunisia is relatively low (0.5-0.7 per 100,000 inhabitants per year). Gender differences were observed regarding anatomical distribution (P = 0.004). Acral lentiginous melanoma (ALM) was the most frequent histological subtype (32.3%); however, nodular melanoma (NM) was the most aggressive and responsible for 54.8% of deaths. CM in XP patients develops at a median age that is 42 years earlier than sporadic cases, with preferential localization on the head and neck (P < 0.001). Finally, male patients exhibited survival disadvantages compared with females (adjusted hazard ratio (HR) = 2.22, 95% CI: 1.05-4.68, P = 0.037). Cutaneous melanoma features in Tunisia are closer to those of non-Caucasians, even though gender differences that are similar to those observed in Caucasians were uncovered. This study also emphasizes the aggressiveness of NM and its effect on melanoma patient deaths. Xeroderma pigmentosum stands as the major predisposing host factor. © 2016 The International Society of Dermatology.

Astroblastoma: a distinct tumor entity characterized by alterations of the X chromosome and MN1 rearrangement.

PubMed

Hirose, Takanori; Nobusawa, Sumihito; Sugiyama, Kazuhiko; Amatya, Vishwa J; Fujimoto, Naomi; Sasaki, Atsushi; Mikami, Yoshiki; Kakita, Akiyoshi; Tanaka, Shinya; Yokoo, Hideaki

2017-10-09

Astroblastoma is a rare, enigmatic tumor of the central nervous system (CNS) which shares some clinicopathologic aspects with other CNS tumors, especially ependymoma. To further clarify the nature of astroblastoma, we performed clinicopathologic and molecular genetic studies on eight cases of astroblastoma. The median age of the patients was 14.5 years, ranging from 5 to 60 years, and seven of the patients were female. All tumors arose in the cerebral hemisphere and radiologically appeared to be well-bordered, nodular tumors often associated with cystic areas and contrast-enhancement. Six of the seven patients with prognosis data survived without recurrences during the follow-up periods ranging from six to 76 months. One patient had multiple recurrences and died six years later. All tumors exhibited salient microscopic features, such as being well demarcated from the surrounding brain tissue, perivascular arrangement of epithelioid tumor cells (represented by "astroblastic" pseudorosettes, trabecular alignment, and pseudopapillary patterns), and hyalinized blood vessels. Immunoreactivity for GFAP, S-100 protein, Olig2, and EMA was variably demonstrated in all tumors, and IDH1 R132H and L1CAM were negative. Array comparative genomic hybridization revealed numerous heterozygous deletions on chromosome X in the four tumors studied, and break-apart fluorescence in situ hybridization demonstrated rearrangement of MN1 in five tumors with successful testing. The characteristic clinicopathologic and genetic findings support the idea that astroblastoma is distinct from other CNS tumors, in particular, ependymoma. In addition, MN1 rearrangement and aberrations of chromosome X may partly be involved in the pathogenesis of astroblastoma. © 2017 International Society of Neuropathology.

The biomedical piglet: establishing reference intervals for haematology and clinical chemistry parameters of two age groups with and without iron supplementation.

PubMed

Ventrella, Domenico; Dondi, Francesco; Barone, Francesca; Serafini, Federica; Elmi, Alberto; Giunti, Massimo; Romagnoli, Noemi; Forni, Monica; Bacci, Maria L

2017-01-17

The similarities between swine and humans in physiological and genomic patterns, and the great correlation in size and anatomy, make pigs extremely useful in preclinical studies. New-born piglets can represent a model for congenital and genetic diseases in new-born children. It is known that piglets may have significant differences in clinicopathological results compared to adult pigs. Therefore, adult laboratory reference intervals cannot be applied to piglets. The aim of this study was to compare haematological and chemical variables in piglets of two ages and determinate age-related reference intervals for commercial hybrid young pigs. Blood samples were collected under general anaesthesia from 130 animals divided into five- (P5) and 30- (P30) day-old piglets. Only P30 animals were treated with parenteral iron after birth. Samples were analysed using automated haematology (ADVIA 2120) and chemistry analysers, and age-related reference intervals were calculated. Significant higher values of RBC, Hb and HCT were observed in P30 animals when compared to P5, with an opposite trend for MCV. These results were associated with a reduction of the RBC regeneration process and the thrombopoietic response. The TSAT and TIBC were significantly higher in P30 compared to P5; however, piglets remained iron deficient compared to adult reference intervals reported previously. In conclusion, this paper emphasises the high variability occurring in clinicopathological variables between new-born and 30-day-old pigs, and between piglets and adult pigs. This study provides valuable reference data for piglets at precise ages and could be used in the future as historical control improving the Reduction in animal experiments, as suggested by the 3Rs principle.

Correlation of clinicopathologic features and lung squamous cell carcinoma subtypes according to the 2015 WHO classification.

PubMed

Chen, Rongrong; Ding, Zhengping; Zhu, Lei; Lu, Shun; Yu, Yongfeng

2017-12-01

This study aimed to determine the relationship between clinicopathologic features and lung squamous cell carcinoma (LSCC) subtypes according to the 2015 WHO classification. We identified 824 operable LSCC patients undergoing a complete surgical resection at Shanghai Chest Hospital between April 2015 and January 2017. Immunohistochemistry was used to investigate the clinicopathologic features. Among them, the percentages of LSCC subtypes were 66.1% (545/824), 28.6% (236/824), and 5.2% (43/824) for keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), and basaloid squamous cell carcinoma (BSCC), respectively. There were more males, more smokers, and more pneumonectomy surgeries in KSCC patients (p = 0.008, p = 0.000, p = 0.043). There were more N2 lymph node involvement and pathological stage III in NKSCC patients (p = 0.01, p = 0.03). BSCC did not demonstrate specificity to anything, but expressed adenocarcinoma markers more frequently. No significant difference existed between pathological subtypes and other clinicopathologic features, such as age, location type, visceral pleural involvement and lymphovascular invasion. The frequencies of EGFR sensitive mutations and ALK rearrangements were not significantly different among three subtypes. Significant relationships exist between some clinicopathologic features and LSCC subtypes. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Esophagogastrostomy plus gastrojejunostomy: a novel reconstruction procedure after curative resection for proximal gastric cancer.

PubMed

Chen, Shicai; Li, Jianchang; Liu, Haiying; Zeng, Jun; Yang, Guohua; Wang, Jin; Lu, Weiqun; Yu, Nanrong; Huang, Zhiliang; Xu, Houwei; Zeng, Xiang

2014-03-01

The choice of surgical strategy for patients with proximal gastric cancer remains controversial. In this study, we recommend that a new reconstruction procedure be performed following proximal gastrectomy. We conducted a retrospective study involving 71 patients who underwent gastrectomy for proximal gastric cancer. Clinicopathological features, postoperative complications, nutritional status, and overall survival (OS) rate were compared among three different reconstruction approaches. There were 34 cases of proximal gastrectomy followed by esophagogastrostomy reconstruction (EG), 16 cases of total gastrectomy and Roux-en Y reconstruction (RY) and 21 cases of proximal gastrectomy followed by esophagogastrostomy plus gastrojejunostomy reconstruction (EGJ). Though the clinicopathological features, the nutritional status and OS rate were similar among the three groups of patients, the incidence of reflux esophagitis was significantly higher in the EG group (35.3%) than the RY (6.2%) and EGJ (9.6%) groups(P < 0.05). Few EGJ patients suffered from either reflux esophagitis or anastomotic stenosis. The EGJ reconstruction method helps to resolve the syndrome of reflux esophagitis. Our data indicates that it is a simple, safe, and effective reconstruction procedure for PGC.

Predictors of clinical-pathologic stage discrepancy in oral cavity squamous cell carcinoma: A National Cancer Database study.

PubMed

Kılıç, Sarah S; Kılıç, Suat; Crippen, Meghan M; Varughese, Denny; Eloy, Jean Anderson; Baredes, Soly; Mahmoud, Omar M; Park, Richard Chan Woo

2018-04-01

Few studies have examined the frequency and survival implications of clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC). Oral cavity SCC cases with full pathologic staging information were identified in the National Cancer Database (NCDB). Clinical and pathologic stages were compared. Multivariate logistic regressions were performed to identify factors associated with stage discrepancy. There were 9110 cases identified, of which 67.3% of the cases were stage concordant, 19.9% were upstaged, and 12.8% were downstaged. The N classification discordance (28.5%) was more common than T classification discordance (27.6%). In cases of T classification discordance, downstaging is more common than upstaging (15.4% vs 12.1% of cases), but in cases of N classification discordance, the reverse is true; upstaging is much more common than downstaging (20.1 vs 8.4% of cases). Clinicopathologic stage discrepancy in oral cavity SCC is a common phenomenon that is associated with a number of clinical factors and has survival implications. © 2018 Wiley Periodicals, Inc.

Expression of connective tissue growth factor in male breast cancer: clinicopathologic correlations and prognostic value.

PubMed

Lacle, Miangela M; van Diest, Paul J; Goldschmeding, Roel; van der Wall, Elsken; Nguyen, Tri Q

2015-01-01

Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female breast cancer (FBC). The aim of the present study was to investigate clinicopathologic correlations and prognostic value of CTGF in male breast cancer (MBC) and to compare these findings with FBC. For this, we studied CTGF protein expression by immunohistochemistry in 109 MBC cases and 75 FBC cases. In MBC, stromal CTGF expression was seen in the majority of the cases 78% (85/109) with high expression in 31/109 cases (28.4%), but expression in tumor cells was only seen in 9.2% (10/109) of cases. High stromal CTGF expression correlated with high grade and high proliferation index (>15%) assessed by MIB-1 immunohistochemical staining. CTGF expression in tumor epithelial cells did not correlate with any of the clinicopathologic features. In FBC, stromal CTGF expression positively correlated with mitotic count and tumor CTGF expression was associated with triple negative status of the tumor (p = 0.002). Neither stromal nor tumor epithelial cell CTGF expression had prognostic value in MBC and FBC. In conclusion, stromal CTGF expression was seen in a high percentage of MBC and was correlated with high grade and high proliferation index. In view of the important role of the microenvironment in cancer progression, this might suggest that stromal CTGF could be an interesting target for novel therapies and molecular imaging. However, the lack of association with prognosis warrants caution. The potential role of CTGF as a therapeutic target for triple negative FBC deserves to be further studied.

Clinicopathologic Characteristics and Prognosis of Tongue Squamous Cell Carcinoma in Patients with and without a History of Radiation for Nasopharyngeal Carcinoma: A Matched Case-Control Study.

PubMed

Zhang, Peng; Zhang, Li; Liu, Hui; Zhao, Lei; Li, Yong; Shen, Jing-Xian; Liu, Qing; Liu, Meng-Zhong; Xi, Mian

2017-07-01

Previous studies reported an association between an increased risk of tongue cancer and radiation treatment for nasopharyngeal carcinoma (NPC). This study compared the clinicopathologic characteristics and outcomes of tongue squamous cell carcinoma (TSCC) in patients with and without a history of radiotherapy for NPC. From 1965 to 2009, a total of 73 patients were diagnosed with TSCC with a history of radiotherapy for NPC. The patients were matched in a 1:3 ratio with patients with sporadic TSCC according to age, sex, and year of the TSCC diagnosis. The primary endpoint was the overall survival. The median interval from NPC to TSCC was 82 months. The NPC survivors were more likely to be diagnosed with a more advanced T classification, less likely to have lymph node involvement, and more likely to have the tumor located in the dorsum of the tongue than sporadic TSCC. Regarding the histologic characteristics, the NPC survivors were more likely to have a weak lymphocytic host response, low tumor budding, and low risk of a worse pattern of invasion. The sporadic TSCC patients had a better overall survival (hazard ratio, 0.690; p=0.033) than the NPC survivors. In competing risks analysis, the cumulative incidence functions for the competing event (documented non-tongue cancer death) were significantly higher in the NPC survivors (Gray's test, p=0.001). TSCC patients with a history of radiotherapy for NPC appear to have particular clinicopathologic features, a poorer survival, and are more likely to die from non-tongue cancer causes than those with sporadic TSCC.

Demographic and clinicopathological profile of patients with chronic pancreatitis in a tertiary referral teaching hospital of West Bengal: Personal experience.

PubMed

Bhattacharjee, Prosanta Kumar; Mukerjee, Aishik; Adhikary, Chandranath

2015-09-01

There is a paucity of data on the demographic and clinicopathological profiles of patients with chronic pancreatitis from the eastern part of India. This study documents the demographic and clinicopathological profiles of patients with chronic pancreatitis presenting to a general surgery unit of a tertiary referral hospital of Kolkata. The records of 145 patients presenting with chronic pancreatitis over a 5-year period were scrutinized and their demographics, clinical profile, and complications and morphological changes of the pancreas are described. Of the 145 patients, more than 50% were under the age of 30 years. Males were affected more frequently than females (M/F = 3.8:1). While idiopathic pancreatitis was the most common form of chronic pancreatitis (41.4%), alcohol was found to be the most common etiology (37.9%). Pain was the most common presenting symptom (n = 143; 98.6%). Sixty-five subjects (45%) had diabetes of which 32 subjects were insulin-dependent. On contrast-enhanced computed tomography, ductal dilatation was seen in 80 (55.17%) subjects, while ductal calculi and ductal dilatation in 54 cases (37.2%). Parenchymal calcification was seen in 45 patients of whom 40 patients (89%) were under the age of 30 years. Pseudocyst was the most common complication (n = 16) followed by biliary obstruction (n = 8) and portal hypertension (n = 4). Patients with alcoholic pancreatitis had significantly higher frequency of severe abdominal pain, diabetes, and local complications as compared to the other forms of pancreatitis in our study. Idiopathic pancreatitis was the most common form of chronic pancreatitis in this study, followed by alcoholic pancreatitis and then tropical pancreatitis.

Lung Adenocarcinoma With MUC4 Expression Is Associated With Smoking Status, HER2 Protein Expression, and Poor Prognosis: Clinicopathologic Analysis of 338 Cases.

PubMed

Rokutan-Kurata, Mariyo; Yoshizawa, Akihiko; Sumiyoshi, Shinji; Sonobe, Makoto; Menju, Toshi; Momose, Masanobu; Koyama, Mizuki; Shigeto, Shohei; Fujimoto, Masakazu; Zhang, Meng; Morita, Satoshi; Date, Hiroshi; Haga, Hironori

2017-07-01

MUC4 is a transmembrane glycoprotein that plays a role in the cell growth signaling pathway and has been studied in various organ malignancies. This study aimed to analyze MUC4 expression in resected lung adenocarcinomas (ADCs) to define the clinicopathologic characteristics of MUC4-positive cancers. Immunohistochemical MUC4 analysis was performed using tissue microarray slides containing 338 lung ADCs. Associations between MUC4 expression and the following clinicopathologic parameters were evaluated: sex; age; smoking status; tumor stage; tumor grade; lymphovascular invasion; pleural invasion; TTF-1 and HNF4α expression; EGFR, KRAS, BRAF, and HER2 mutation status; and ALK and ROS1 fusion status. Ninety-four tumors (27.8%) were MUC4 positive. Most patients with MUC4-positive tumors were male (P < .001) and smokers (P = .006). Moreover, MUC4 expression was significantly associated with solid ADCs (P < .001) and vascular invasion (P = .001). MUC4 expression inversely correlated with TTF-1 expression (P = .020) and EGFR mutations (P = .004). Interestingly, MUC4 expression correlated with HER2 protein expression (P = .042), although MUC4 expression did not correlate with HER2 DNA amplification or HER2 gene mutations. Patients with MUC4-positive tumors had significantly worse prognoses compared to patients with MUC4-negative tumors (P = .025). The present study showed that MUC4-positive lung ADCs correlated with male smokers, solid ADCs, negative TTF-1 expression, the EGFR wild-type gene, HER2 protein expression, and poorer prognoses. These results suggest that MUC4-positive lung ADC may be a distinct subtype found in patients with smoking-related poor outcomes, mediated by HER2 signaling pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence and clinicopathologic features of CD30-positive de novo diffuse large B-cell lymphoma in Chinese patients: a retrospective study of 232 cases

PubMed Central

Gong, Qi-Xing; Lu, Ting-Xun; Liu, Chong; Wang, Zhen; Liang, Jin-Hua; Xu, Wei; Li, Jian-Yong; Zhang, Zhi-Hong; Chen, Qi

2015-01-01

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease that great efforts had been made in to build up molecular and immunophenotypic subgroups that could relatively accurate indicate prognosis and give clue to therapy. Recently, CD30 was reported as a useful predictor with favorable clinical outcome. However, CD30 expression patterns and the clinicopathologic features of CD30 positive DLBCL are not well described thus far, especially in Asian patients. Here, we studied 232 cases of de novo DLBCL in East China to investigate the prevalence and clinicopathological features of CD30-positive DLBCL using a panel of immunohistochemical markers. Applying a >0% threshold, CD30 was expressed in approximately 12% patients with Epstein-Barr virus (EBV) negative DLBCL, affecting younger people and showing a lower frequency of BCL2 expression and MYC/BCL2 co-expression. Patients with CD30-positive DLBCLs showed better progression-free survival and overall survival compared with patients with CD30-negative DLBCLs, although the superior outcome of CD30 positivity had minimal effects on BCL2+ DLBCL or DLBCL with MYC/BCL2 co-expression. Moreover, CD30 could express in CD5+ DLBCL. We concluded that CD30 may be useful as a prognostic marker in rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treated DLBCLs, indicating favorable outcomes in a Chinese population. Further studies with larger samples should be performed to investigate the function of CD30 expression in BCL2+ DLBCLs, DLBCLs with MYC/BCL2 co-expression, and CD5+ DLBCLs, and to evaluate the feasibility of anti-CD30 targeted treatment in DLBCL therapy. PMID:26884853

Clinicopathological patterns and distribution of Schistosomiasis in Asir Region.

PubMed

Morad, N A; Khan, A R

2001-06-01

The objective of this study is to report, for the first time, the histopathologic pattern of Schistosomiasis from the Asir Region and to compare it to patterns reported from other regions of the Kingdom of Saudi Arabia. Several studies have reported the patterns of Schistosomiasis in other regions of the Kingdom of Saudi Arabia and other countries where Schistosomiasis is endemic. Schistosomiasis is endemic in certain areas of Asir region, however no data is available concerning the clinicopathological pattern of Schistosomiasis in the Asir Region. This is a retrospective analysis of 217 cases of Schistosomiasis from surgical and biopsy files of Asir Central Hospital during a period from January 1990 to October 1999. Our study revealed that Schistosomiasis was more common among the expatriate population of Asir Region than Saudi nationals residing in this area. The urinary tract was most commonly involved, and then in descending frequency came the vermiform appendix, liver and large bowel. These findings are somewhat different from those observed in the Riyadh Region where the vermiform appendix was the most commonly affected organ. Based on the histopathologic pattern, our study describes the pattern of Schistosomiasis in the Asir Region and may serve as a base-line for future research work.

Impact of acetylsalicylic Acid on the clinicopathological characteristics and prognosis of patients with invasive breast cancer.

PubMed

Sendur, Mehmet A N; Aksoy, Sercan; Ozdemir, Nuriye Y; Zengin, Nurullah; Altundag, Kadri

2014-04-01

The impact of acetylsalicylic acid (ASA) on the clinicopathological characteristics of breast cancer has not yet been elucidated in detail; we therefore aimed to investigate the effects of ASA on the clinicopathological characteristics of patients with breast cancer. Patients diagnosed with breast cancer were retrospectively analyzed. Breast cancer patients who were taking ASA at the time of breast cancer diagnosis were enrolled as ASA users (n = 84); matching patients with the same age who were not taking ASA were included as control group (n = 890). The median age was 56 (range 34-82) years in both groups. ASA users had a significantly lower incidence of grade II-III tumors compared to non-users (P = 0.02). The other clinicopathological characteristics and treatment histories were similar in both groups. In patients using ASA, the disease-free survival (DFS) rate was 97.3%, 89.4%, and 79.9% and in non-users it was 94.1%, 81.8%, and 70.9% in the 1rst, 3rd, and 5th year, respectively (P = 0.01). In aspirin users, the overall survival rate was 95.0%, 90.6%, and 87.6% and in non-users it was 98.1%, 91.2%, and 85.5% in the 1rst, 3rd, and 5th year, respectively (P = 0.50). Using ASA at the time of breast cancer diagnosis was associated with significantly improved DFS in breast cancer patients.

Cutaneous metastasis of signet-ring gastric adenocarcinoma to the breast with unusual clinicopathological features.

PubMed

Avgerinou, Georgia; Flessas, Ioannis; Hatziolou, Eftychia; Zografos, Georgios; Nitsios, Ilias; Zagouri, Flora; Katsambas, Andreas; Kanitakis, Jean

2011-06-01

Cutaneous metastasis of gastric adenocarcinoma is rare and usually presents in men, as nodules over the abdomen. We present the case of a woman with cutaneous metastasis of gastric adenocarcinoma showing unusual clinicopathological features. A 37-year-old woman developed florid cutaneous metastasis over the skin of the left breast two years after total gastrectomy for a signet-ring adenocarcinoma of the diffuse type. The metastasis presented as a multinodular growth developing over erythematous skin of the left hemithorax. Microscopically, the skin tumor was predominantly made up of spindle-shaped cells, mimicking a mesenchymal/fibrohistiocytic neoplasm. A comparative immunohistochemical study of the gastric primary and the skin tumor showed an almost identical profile (keratin 7/20+; epithelial membrane antigen+, MUC-5AC+), highlighting the gastric adenocarcinoma as the origin of the skin metastasis. Although rare, cutaneous metastases of gastric adenocarcinomas can develop in women and may mimic inflammatory metastasis of breast adenocarcinoma. Immunohistochemistry is invaluable in establishing the correct diagnosis.

Loss of gastric gland mucin-specific O-glycan is associated with progression of differentiated-type adenocarcinoma of the stomach.

PubMed

Shiratsu, Kazuo; Higuchi, Kayoko; Nakayama, Jun

2014-01-01

Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides having terminal α1,4-linked N-acetylglucosamine (αGlcNAc) residues largely attached to a MUC6 scaffold. Previously, we generated A4gnt-deficient mice, which totally lack αGlcNAc, and showed that αGlcNAc functions as a tumor suppressor for gastric cancer. Here, to determine the clinicopathological significance of αGlcNAc in gastric carcinomas, we examined immunohistochemical expression of αGlcNAc and mucin phenotypic markers including MUC5AC, MUC6, MUC2, and CD10 in 214 gastric adenocarcinomas and compared those expression patterns with clinicopathological parameters and cancer-specific survival. The αGlcNAc loss was evaluated in MUC6-positive gastric carcinoma. Thirty-three (61.1%) of 54 differentiated-type gastric adenocarcinomas exhibiting MUC6 in cancer cells lacked αGlcNAc expression. Loss of αGlcNAc was significantly correlated with depth of invasion, stage, and venous invasion by differentiated-type adenocarcinoma. Loss of αGlcNAc was also significantly associated with poorer patient prognosis in MUC6-positive differentiated-type adenocarcinoma. By contrast, no significant correlation between αGlcNAc loss and any clinicopathologic variable was observed in undifferentiated-type adenocarcinoma. Expression of MUC6 was also significantly correlated with several clinicopathological variables in differentiated-type adenocarcinoma. However, unlike the case with αGlcNAc, its expression showed no correlation with cancer-specific survival in patients. In undifferentiated-type adenocarcinoma, we observed no significant correlation between mucin phenotypic marker expression, including MUC6, and any clinicopathologic variable. These results together indicate that loss of αGlcNAc in MUC6-positive cancer cells is associated with progression and poor prognosis in differentiated, but not undifferentiated, types of gastric adenocarcinoma. © 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

The predictive factors for lymph node metastasis in early gastric cancer: A clinical study.

PubMed

Wang, Yinzhong

2015-01-01

To detect the clinicopathological factors associated with lymph node metastases in early gastric cancer. We retrospectively evaluated the distribution of metastatic nodes in 198 patients with early gastric cancer treated in our hospital between May 2008 and January 2015, the clinicopathological factors including age, gender, tumor location, tumor size, macroscopic type, depth of invasion, histological type and venous invasion were studied, and the relationship between various parameters and lymph node metastases was analyzed. In this study, one hundred and ninety-eight patients with early gastric cancer were included, and lymph node metastasis was detected in 28 patients. Univariate analysis revealed a close relationship between tumor size, depth of invasion, histological type, venous invasion, local ulceration and lymph node metastases. Multivariate analysis revealed that the five factors were independent risk factors for lymph node metastases. The clinicopathological parameters including tumor size, depth of invasion, local ulceration, histological type and venous invasion are closely correlated with lymph node metastases, should be paid high attention in early gastric cancer patients.

Therapeutic strategies and genetic profile comparisons in small cell carcinoma and large cell neuroendocrine carcinoma of the lung using next-generation sequencing.

PubMed

Ito, Masaoki; Miyata, Yoshihiro; Hirano, Shoko; Kimura, Shingo; Irisuna, Fumiko; Ikeda, Kyoko; Kushitani, Kei; Tsutani, Yasuhiro; Ueda, Daisuke; Tsubokawa, Norifumi; Takeshima, Yukio; Okada, Morihito

2017-12-12

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung are classified as variants of endocrine carcinoma and subdivided into pure or combined type. Clinical benefit of target therapy has not been established in these tumors. This study aimed to compare genetic and clinicopathological features between SCLC and LCNEC or pure and combined types, and explore the possibility of target therapy using next-generation sequencing. In 13 SCLC and 22 LCNEC cases, 72 point mutations, 19 deletions, and 3 insertions were detected. As therapeutically targetable variants, mutations in EGFR (L858R), KRAS (G12D, G12A, G12V), and PIK3CA (E545K) were detected in 5 cases. The case harboring EGFR mutation showed response to EGFR-tyrosine kinase inhibitor. However, there are no clinicopathological features associated with therapeutically targetable cases. And there was no significant genetic feature between SCLC and LCNEC or pure and combined types. In conclusion, although patients with SCLC and LCNEC may benefit from target therapy, they were not identifiable by clinicopathologic background. And there was not significant genetic difference between SCLC and LCNEC, including between pure and combined types. Classifying SCLC and LCNEC in same category is reasonable. However, distinguishing the pure type from combined type was not validated. Comprehensive genetic analysis should be performed to detect targetable variants in any type of SCLC and LCNEC.

Association of microRNA-200c expression levels with clinicopathological factors and prognosis in endometrioid endometrial cancer.

PubMed

Wilczynski, Milosz; Danielska, Justyna; Domanska-Senderowska, Daria; Dzieniecka, Monika; Szymanska, Bozena; Malinowski, Andrzej

2018-05-01

MicroRNAs (miRNAs) are regulators of gene expression, which play an important role in many critical cellular processes including apoptosis, proliferation and cell differentiation. Aberrant miRNA expression has been reported in a variety of human malignancies. Therefore, miRNAs may be potentially used as cancer biomarkers. miRNA-200c, which is a member of the miRNA-200 family, might play an essential role in tumor progression. The purpose of this study was to evaluate the prognostic and clinical significance of miRNA-200c in women with endometrioid endometrial cancer. Total RNA extraction from 90 archival formalin-fixed paraffin-embedded tissue samples of endometri-oid endometrial cancer and 10 normal endometrium samples was performed. After cDNA synthesis, real-time polymerase chain reaction was conducted and relative expression of miRNA-200c was assessed. Then, miRNA-200c expression levels were evaluated with regard to clinicopathological characteristics. The expression levels of miRNA-200c were significantly increased in endometrioid endometrial cancer samples. Expression of miRNA-200c maintained at significantly higher levels in the early stage endometrioid endometrial cancer compared with more advanced stages. In the Kaplan-Meier analysis, lower levels of miRNA-200c expression were associated with inferior survival. Expression levels of miRNA-200c might be associated with clinicopathological factors and survival in endometrioid endometrial cancer. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

PubMed

Rakha, E A; Soria, D; Green, A R; Lemetre, C; Powe, D G; Nolan, C C; Garibaldi, J M; Ball, G; Ellis, I O

2014-04-02

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods. In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes. Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

The Clinicopathological Factors Associated with Disease Progression in Luminal A Breast Cancer and Characteristics of Metastasis: A Retrospective Study from A Single Center in China.

PubMed

Ye, Jingming; Wang, Wenjun; Xin, Ling; Owen, Sioned; Xu, Ling; Duan, Xuening; Cheng, Yuanjia; Zhang, Hong; Zhang, Shuang; Li, Ting; Liu, Yinhua

2017-08-01

This study investigated the clinicopathological factors associated with outcomes in patients with Luminal A breast cancer. Retrospective analysis of the association of clinicopathological factors and breast cancer outcome in 421 patients with newly-diagnosed Luminal-A breast cancer that were enrolled from January 2008 to December 2014. Clinicopathological data were analyzed to validate the relationship with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves and log-rank tests were used to analyze the value of clinicopathological factors (tumor size, node status and lymphovascular invasion), and subsequent Cox regression analysis revealed significant prognostic factors. With a median of 61 months follow-up, the 5-year DFS and 5-year OS rate were 98.3% and 99.3%. Cox multivariate regression analysis showed that clinical anatomic stage, tumor size, status of lymph nodes, lymphovascular invasion and systemic treatment are strong prognostic factors for clinical outcome in patients with Luminal-A breast cancer. Of all 413 patients with stage I-III breast cancer, 14 presented with metastasis (3.4%) during the follow up. Bone (6/14, 42.9%) was the most common site of metastasis followed by liver (5/14, 35.7%) and lung (4/14, 28.6%). The median survival time after metastasis was 20.4 months. Of all the sites of distant metastasis, liver metastasis was the only factor that affected survival time after metastasis (χ 2 =6.263, p=0.012). Patients with Luminal A breast cancer have excellent outcomes. Liver metastasis is an important factor compressing the survival time after distant metastasis presents. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Difference in Postsurgical Prognostic Factors between Lung Adenocarcinoma and Squamous Cell Carcinoma

PubMed Central

Sakai, Hiroki; Kimura, Hiroyuki; Miyazawa, Tomoyuki; Marushima, Hideki; Saji, Hisashi

2017-01-01

Purpose: The aim of this study was to compare the clinicopathologic prognostic factors between patients who underwent lung resection for adenocarcinoma (AD) and those with squamous cell carcinoma (SQ). Methods: A database of patients with lung AD or SQ who underwent surgery with curative intent in our department from January 2008 to December 2014 was reviewed. Associations between various clinicopathologic factors, postsurgical recurrence-free survival (RFS), and overall survival (OS) were analyzed to find significant prognostic factors. Results: A total of 537 lung cancer patients (AD, 434; SQ, 103) were included in this study. Although RFS was similar in patients with AD and SQ, OS was significantly poorer in those with SQ. Multivariate analysis in patients with AD revealed that age (≥69 vs. <69), lymphatic invasion, and histologic pleural invasion (p0 vs. p1–3) were associated with RFS, while gender and pleural invasion were associated with OS. In SQ, however, smoking, clinical stage, and pulmonary metastasis were associated with RFS in the multivariate analysis. Conclusion: Since significant postoperative prognostic factors are quite different between lung AD and SQ, these two histologic types should be differently analyzed in a clinical study. PMID:28966230

Clinico-pathological study to evaluate oral lichen planus for the establishment of clinical and histopathological diagnostic criteria.

PubMed

Hiremath, Santhosh; Kale, Alka D; Hallikerimath, Seema

2015-01-01

Lichen planus and lichenoid lesions affecting the oral cavity show similar clinico-pathological features creating a diagnostic dilemma. Hence, the aim of the present study was to establish a clinical and histopathological correlation in the diagnosis of oral lichen planus, based on the modified WHO diagnostic criteria of oral lichen planus and oral lichenoid lesions proposed by Van der Meij and Van der Waal in 2003. In the present study, 100 cases of oral lichen planus were clinically and histopathologically analyzed. Out of the 100 cases, 50 were prospective and 50 were retrospective cases. Prospective cases were collected based on the clinical diagnosis of oral lichen planus and oral lichenoid lesion. Retrospective cases were collected based on the histopathological diagnosis of oral lichen planus. Both the clinical and histopathological analyses were performed based on a proposal for a set of modified diagnostic criteria of oral lichen planus and oral lichenoid lesion. A final diagnosis of oral lichen planus was made only after the correlation of the clinical diagnosis with the histopathological diagnosis. The interobserver agreement among three observers for both prospective and retrospective cases in the final diagnosis of oral lichen planus was found to be "good" to "very good" indicating high reproducibility. However, the final diagnoses of true oral lichen planus after clinico-pathological correlation in prospective and retrospective study groups appeared to be 38.0% and 54.0% respectively. The results of the present study revealed mild to moderate clinico-pathological correlation in the final diagnosis of oral lichen planus for the prospective and retrospective study groups respectively.

Clinicopathological differences between familial colorectal cancer type X and sporadic cancer in an isolated area of spain.

PubMed

Medina-Arana, V; Rahy-Martín, A; Delgado-Plasencia, L; Martínez-Riera, A; León-Ayllón, D; Rodríguez-Castellano, D; Bravo-Gutiérrez, A; Fernández-Peralta, A; González-Aguilera, J J

2016-11-01

Very few studies have compared the epidemiological characteristics of patients with familial colorectal cancer Type X (FCCTX) with those of sporadic colorectal cancer (S-CRC). The aim of this study was to compare clinicopathological characteristics and survival between FCCTX and S-CRC in patients from a historically isolated geographical region. A retrospective study was carried out of patients with S-CRC and FCCTX treated in the Canary Islands. Family and personal history of colorectal cancer (CRC) were recorded, together with genetic (microsatellite instability), immunohistochemical and clinical variables. Forty-eight (10.6%) of 451 patients were classified as FCCTX and the remaining 403 (89.4%) as S-CRC. Age at the diagnosis of tumour was significantly lower in FCCTX than in S-CRC (64.06 ± 12.65 years vs 69.13 ± 10.80 years; P = 0.01; Z = -2.48). Patients with FCCTX had a larger number of synchronous tumours (P = 0.09). Recurrence was significantly higher in FCCTX than in S-CRC (18.7% vs 8.6%; P = 0.01). Survival correlated significantly with the number of first-degree and second-degree relatives with CRC (P = 0.04; OR: 1.368, 95% CI: 1.01-1.84, and P = 0.04; OR: 1.363, 95% CI: 1.08-1.65) and with the total number of cases of CRC in the immediate family (P < 0.01; OR: 1.377, 95% CI: 1.17-1.61). Recurrence-free time was significantly lower in patients with FCCTX (log-rank = 0.01). Significant differences were found in several demographic and clinicopathological variables between patients with FCCTX and patients with S-CRC. These included increased tumour presentation under the age of 50 years and a higher recurrence rate in patients with FCCTX, suggesting an increased risk of CRC in this group. Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.

Education Level Is a Strong Prognosticator in the Subgroup Aged More Than 50 Years Regardless of the Molecular Subtype of Breast Cancer: A Study Based on the Nationwide Korean Breast Cancer Registry Database.

PubMed

Hwang, Ki-Tae; Noh, Woochul; Cho, Se-Heon; Yu, Jonghan; Park, Min Ho; Jeong, Joon; Lee, Hyouk Jin; Kim, Jongjin; Oh, Sohee; Kim, Young A

2017-10-01

This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (< 12 years). Survival analyses were performed with respect to the overall survival between the two groups. A high EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group.

Education Level Is a Strong Prognosticator in the Subgroup Aged More Than 50 Years Regardless of the Molecular Subtype of Breast Cancer: A Study Based on the Nationwide Korean Breast Cancer Registry Database

PubMed Central

Hwang, Ki-Tae; Noh, Woochul; Cho, Se-Heon; Yu, Jonghan; Park, Min Ho; Jeong, Joon; Lee, Hyouk Jin; Kim, Jongjin; Oh, Sohee; Kim, Young A

2017-01-01

Purpose This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. Materials and Methods The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (< 12 years). Survival analyses were performed with respect to the overall survival between the two groups. Results A high EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. Conclusion The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group. PMID:28161933

Relationship between lymphovascular invasion and clinicopathological features of papillary thyroid carcinoma

PubMed Central

Sezer, Atakan; Celik, Mehmet; Bulbul, Buket Yilmaz; Can, Nuray; Tastekin, Ebru; Ayturk, Semra; Ustun, Funda; Guldiken, Sibel; Sut, Necdet

2017-01-01

Lymphovascular invasion (LVI) is an important prognostic factor in various solid tumors, however, data on the association between LVI and thyroid carcinomas are limited. In this study, we evaluated the relationship between LVI and clinicopathological features of papillary thyroid carcinoma (PTC). Six hundred seventy-eight patients diagnosed with PTC between 2012 and 2015 were included into the study. Patients were classified based on the presence or absence of LVI. Gender, age, ultrasonography (US), tumor size and multifocality, BRAFV600E mutation, perineural and capsular invasion, extrathyroid extension (ETE), nodal metastasis, and recurrences were evaluated, and risk analysis was performed for each parameter. The number of patients with LVI [LVI (+)] was 63, while the number of patients without LVI [LVI (-)] was 615. The female/male ratio was 564/114. LVI was present in 18.4% of male patients and in 7.4 % of female patients. In the age group between 17-25 years LVI was detected in 6/13 patients, and this result was statistically significant compared to other age groups (p = 0.004). Suspicious lymph nodes upon US, perineural or capsular invasion, ETE, tumor size, and nodal metastasis were significantly more frequent in LVI (+) group (p < 0.001). The frequency of BRAFV600E mutation was also significantly higher in LVI (+) group (p < 0.001). Overall, the presence of LVI was associated with gender, tumor size, age, lymph node metastasis, pathological lymph nodes, perineural and capsular invasion, ETE, and BRAFV600E mutation. These results suggest that in PTC patients undergoing thyroidectomy, the presence of LVI should be considered as an indicator of aggressive clinicopathological features and those patients should be followed up carefully for recurrences and metastasis. PMID:28284178

Clinicopathological Characteristics and Prognostic Value of Signet Ring Cells in Gastric Carcinoma: A Meta-Analysis.

PubMed

Nie, Run-Cong; Yuan, Shu-Qiang; Li, Yuan-Fang; Chen, Yong-Ming; Chen, Xiao-Jiang; Zhu, Bao-Yan; Xu, Li-Pu; Zhou, Zhi-Wei; Chen, Shi; Chen, Ying-Bo

2017-01-01

Background and Objectives: Previous studies of the prognostic value of the signet ring cell (SRC) type have yielded inconsistent results. Therefore, the aim of the present meta-analysis is to explore the clinicopathological characteristics and prognostic value of SRCs. Methods: Relevant articles that compared SRC and non-SRC type in PubMed and Web of Science were comprehensively searched. Then, a meta-analysis was performed. Results: A total of 19 studies including 35947 cases were analyzed. Compared with non-SRC patients, SRC patients tended to be younger (WMD: -3.88, P=0.001) and predominantly female (OR: 1.60, P<0.001). Additionally, SRC patients exhibited less upper third tumor location (OR: 0.62, P<0.001) and less frequent hematogenous metastasis (OR: 0.41, P<0.001). There was no difference in overall survival (OS) between SRC and non-SRC patients in the total population (HR: 1.02, P=0.830). Early gastric cancer with SRCs was associated with better OS (HR: 0.57, P=0.002), while advanced gastric cancer with non-SRCs was associated with a worse prognosis (HR: 1.17, P<0.001). Conclusions: This meta-analysis revealed that SRC tends to affect young females and tends to be located in the middle and lower third of the stomach. Early SRCs are associated with better prognoses, while advanced SRCs are associated with worse prognoses.

Value of α-fetoprotein in association with clinicopathological features of hepatocellular carcinoma

PubMed Central

Liu, Chang; Xiao, Guang-Qin; Yan, Lu-Nan; Li, Bo; Jiang, Li; Wen, Tian-Fu; Wang, Wen-Tao; Xu, Ming-Qing; Yang, Jia-Yin

2013-01-01

AIM: To explore the relationship between α-fetoprotein (AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma (HCC) thoroughly. METHODS: A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study. The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis, such as status of hepatitis B virus (HBV) infection, tumor size, tumor number, vascular invasion and degree of tumor differentiation. Also, patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP (≤ 20 μg/L, 21-400 μg/L, 401-800 μg/L, and ≥ 801 μg/L), to compare the positive rate of patient among four groups stratified by various clinicopathological variables. And the correlation of different kinds of tumor staging systems, such as TNM, Barcelona Clinic Liver Cancer (BCLC) staging classification and China staging, were compared with the serum concentration of AFP. RESULTS: A total of 2304 HCC patients were enrolled in this study totally; the mean serum level of AFP was 555.3 ± 546.6 μg/L. AFP levels were within the normal range (< 20 μg/L) in 27.4% (n = 631) of all the cases. 81.4% (n = 1875) patients were infected with HBV, and those patients had much higher serum AFP level compared with non-HBV infection ones (573.9 ± 547.7 μg/L vs 398.4 ± 522.3 μg/L, P < 0.001). The AFP level in tumors ≥ 10 cm (808.4 ± 529.2 μg/L) was significantly higher (P < 0.001) than those with tumor size 5-10 cm (499.5 ± 536.4 μg/L) and with tumor size ≤ 5 cm (444.9 ± 514.2 μg/L). AFP levels increased significantly in patients with vascular invasion (694.1 ± 546.9 μg/L vs 502.1 ± 543.1 μg/L, P < 0.001). Patients with low tumor cell differentiation (559.2 ± 545.7 μg/L) had the significantly (P = 0.007) highest AFP level compared with high differentiation (207.3 ± 420.8 μg/L) and intermediate differentiation (527.9 ± 538.4 μg/L). In the multiple variables analysis, low tumor cell differentiation [OR 6.362, 95%CI: 2.891-15.382, P = 0.006] and tumor size (≥ 10 cm) (OR 5.215, 95%CI: 1.426-13.151, P = 0.012) were independent predictors of elevated AFP concentrations (AFP > 400 μg/L). Serum AFP levels differed significantly (P < 0.001) in the D stage of BCLC (625.7 ± 529.8 μg/L) compared with stage A (506.2 ± 537.4 μg/L) and B (590.1 ± 551.1 μg/L). CONCLUSION: HCC differentiation, size and vascular invasion have strong relationships with AFP, poor differentiation and HCC size ≥ 10 cm are independent predictors of elevated AFP. BCLC shows better relationship with AFP PMID:23555170

Permanent alopecia in patients with breast cancer after taxane chemotherapy and adjuvant hormonal therapy: Clinicopathologic findings in a cohort of 10 patients.

PubMed

Fonia, Athina; Cota, Carlo; Setterfield, Jane F; Goldberg, Lynne J; Fenton, David A; Stefanato, Catherine M

2017-05-01

Anagen effluvium with reversible scalp alopecia is a known side effect of chemotherapy. However, there are an increasing number of reports in the literature documenting permanent alopecia in patients treated with taxanes. We sought to describe the clinicopathologic features in breast cancer patients who underwent treatment with taxanes and adjuvant hormonal chemotherapy. We reviewed the clinical and histopathologic information of a cohort of 10 patients treated with taxanes and adjuvant hormonal chemotherapy. We have observed 3 types of clinical patterns of alopecia (types A, B, and C), and have validated the histopathologic features showing alopecia areata-like and female pattern hair loss. The study was based on a small sample size and retrospective retrieval of clinical information and histopathologic review of posttreatment slides. We hypothesize a clinicopathologic model of hair follicle cycle disruption in response to the chemoinflammatory and hormonal insults to the hair follicles resulting in permanent alopecia. Clinicopathologic correlation is paramount to the understanding of the morphobiologic pathways in chemotherapy-induced alopecia caused by taxanes and adjuvant hormonal treatment. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of Clinicopathologic Features and Survival of Histopathologically Amelanotic and Pigmented Melanomas: A Population-Based Study

PubMed Central

Thomas, Nancy E.; Kricker, Anne; Waxweiler, Weston T.; Dillon, Patrick M.; Busam, Klaus J.; From, Lynn; Groben, Pamela A.; Armstrong, Bruce K.; Anton-Culver, Hoda; Gruber, Stephen B.; Marrett, Loraine D.; Gallagher, Richard P.; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A.; Orlow, Drs. Irene; Paine, Susan; Ollila, David W.; Reiner, Anne S.; Luo, Li; Hao, Honglin; Frank, Jill S.; Begg, Colin B.; Berwick, Marianne

2014-01-01

Importance Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathology review, or no adjustment for stage limit interpretation or generalization of results from prior studies. Objective To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study. Design Survival analysis with median follow-up of 7.6 years. Setting The Genes, Environment, and Melanoma study enrolled incident cases of melanoma diagnosed in 1998-2003 from international population-based cancer registries. Participants A total of 2,995 patients with 3,486 invasive primary melanomas centrally scored for histologic pigmentation. Main Outcomes and Measurements Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively. Results Eight percent of melanomas (275 of 3,467) were histopathologically amelanotic. Female sex, nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a co-existing nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally of a higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (P for trend <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than pigmented melanoma [hazard ratio (HR), 2.0; 95% confidence interval (CI), 1.4-3.0; P< .001], adjusted for age, sex anatomic site, and study design variables; but survival did not differ once AJCC tumor stage was also taken into account, (HR, 0.8; 95% CI, 0.5-1.2; P = .36). Conclusions and Relevance At the population level, survival after diagnosis of amelanotic melanoma is poorer than after pigmented melanoma because of its more advanced stage at diagnosis. It is probable that amelanotic melanomas present at more advanced tumor stages because they are difficult to diagnose. The association of amelanotic melanoma with presence of mitoses independently of Breslow thickness and other clinicopathologic characteristics suggests that amelanotic melanomas might also grow faster than pigmented melanomas. New strategies for early diagnosis and investigation of the biology of amelanotic melanoma are warranted. PMID:25162299

EBV-Positive T/NK-Cell Lymphoproliferative Disease of Childhood

PubMed Central

Hong, Mineui; Yoo, Keon Hee; Koo, Hong Hoe; Kim, Seok Jin; Kim, Won Seog

2013-01-01

Background Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality. Methods Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed. Results STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis. Conclusions EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment. PMID:23667373

EBV-Positive T/NK-Cell Lymphoproliferative Disease of Childhood.

PubMed

Hong, Mineui; Ko, Young Hyeh; Yoo, Keon Hee; Koo, Hong Hoe; Kim, Seok Jin; Kim, Won Seog; Park, Heejung

2013-04-01

Epstein-Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH), EBV-positive systemic T-cell lymphoproliferative disease (STLPD) of childhood, and chronic active EBV (CAEBV) infection may develop after primary EBV infection. This study reviewed the clinicopathological spectrum of EBV-associated T- and natural killer (NK)-cell LPD, including STLPD and CAEBV infection, with an analysis of T-cell clonality. Clinicopathological features of seven patients with EBV-associated HLH or STLPD and 12 patients with CAEBV infection were reviewed. Immunohistochemical staining and a T-cell receptor (TCR) gene rearrangement study were performed. STLPD and EBV-positive HLH showed significantly overlapping clinicopathological findings. One patient with STLPD and one patient with EBV-positive HLH demonstrated moderate to severe atypia of the infiltrating lymphocytes, whereas the remaining patients lacked significant atypia. Twelve patients had CAEBV infection, four of whom suffered mosquito-bite hypersensitivity, five showed NK lymphocytosis, and one suffered hydroa vacciniforme. Infiltrating lymphocytes were predominantly small and devoid of atypia. Hemophagocytic histiocytosis was found in seven of 11 patients. Monoclonality was detected in three (50%) of the six patients with successful TCR gene analysis. EBV-positive HLH and STLPD share similar clinicopathological findings and may constitute a continuous spectrum of acute EBV-associated T- or NK-cell proliferative disorders. The distinction of EBV-positive T-cell LPD from EBV-positive HLH may be difficult during routine diagnoses because of the technical limitations of clonality assessment.

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) expression in colorectal cancer.

PubMed

Nagano, Hideki; Goi, Takanori; Koneri, Kenji; Hirono, Yasuo; Katayama, Kanji; Yamaguchi, Akio

2007-12-01

Vascular endothelial growth factor (VEGF) is known as an important factor in the growth and metastasis of cancer cells. In 2001, a novel angiogenesis factor, endocrine gland-derived vascular endothelial growth factor (EG-VEGF), was cloned. In this study, we investigated the expression of EG-VEGF in colorectal cancer, the relationship between its expression and clinicopathological factors, and the in vitro activity of EG-VEGF transfectants. We determined expression levels of EG-VEGF in 113 advanced colorectal cancers resected in our hospital by quantitative PCR, and compared the expression levels and clinicopathological findings by multivariate analyses. The expression of EG-VEGF mRNA was positive in 31 cancers and negative in 82 cancers. We found that compared with the negative expression of the EG-VEGF gene, its positive expression was more frequently associated with hematogenous metastasis, and was associated with a poorer survival rate. In addition, EG-VEGF transfectants showed a higher degree of in vitro tubular formation than control cells. We speculate that, in colorectal cancers, the EG-VEGF gene functions as an important factor in angiogenesis in primary and metastatic lesions, and consider that it is useful as a novel prognostic factor. EG-VEGF molecule-targeted therapy has the potential for improving survival rates.

Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer

PubMed Central

Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Yuan, Yuan

2017-01-01

Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival. PMID:28350854

Clinicopathological comparison of colorectal and endometrial carcinomas in patients with Lynch-like syndrome versus patients with Lynch syndrome.

PubMed

Mas-Moya, Jenny; Dudley, Beth; Brand, Randall E; Thull, Darcy; Bahary, Nathan; Nikiforova, Marina N; Pai, Reetesh K

2015-11-01

Screening for DNA mismatch repair (MMR) deficiency in colorectal and endometrial carcinomas identifies patients at risk for Lynch syndrome. Some patients with MMR-deficient tumors have no evidence of a germline mutation and have been described as having Lynch-like syndrome. We compared the clinicopathological features of colorectal and endometrial carcinomas in patients with Lynch-like syndrome and Lynch syndrome. Universal screening identified 356 (10.6%) of 3352 patients with colorectal carcinoma and 72 (33%) of 215 patients with endometrial carcinoma with deficient DNA MMR. Sixty-six patients underwent germline mutation analysis with 45 patients (68%) having evidence of a germline MMR gene mutation confirming Lynch syndrome and 21 patients (32%) having Lynch-like syndrome with no evidence of a germline mutation. Most patients with Lynch-like syndrome had carcinoma involving the right colon compared to patients with Lynch syndrome (93% versus 45%; P < .002). All patients with colorectal carcinomas demonstrating isolated loss of MSH6 expression had Lynch syndrome confirmed by germline mutation analysis. Synchronous or metachronous Lynch syndrome-associated carcinoma was more frequently identified in patients with Lynch syndrome compared to Lynch-like syndrome (38% versus 7%; P = .04). There were no significant differences in clinicopathological variables between patients with Lynch-like syndrome and Lynch syndrome with endometrial carcinoma. In summary, 32% of patients with MMR deficiency concerning Lynch syndrome will have Lynch-like syndrome. Our results demonstrate that patients with Lynch-like syndrome are more likely to have right-sided colorectal carcinoma, less likely to have synchronous or metachronous Lynch syndrome-associated carcinoma, and less likely to demonstrate isolated loss of MSH6 expression within their tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinicopathologic implications of DNA mismatch repair status in endometrial carcinomas.

PubMed

Shikama, Ayumi; Minaguchi, Takeo; Matsumoto, Koji; Akiyama-Abe, Azusa; Nakamura, Yuko; Michikami, Hiroo; Nakao, Sari; Sakurai, Manabu; Ochi, Hiroyuki; Onuki, Mamiko; Satoh, Toyomi; Oki, Akinori; Yoshikawa, Hiroyuki

2016-02-01

Endometrial carcinoma is the most common malignancy in women with Lynch syndrome caused by mismatch repair (MMR) deficiency. We investigated the clinicopathologic significance of deficient MMR and Lynch syndrome presumed by MMR analyses in unselected endometrial carcinomas. We analyzed immunohistochemistry of MMR proteins (MLH1/MSH2/MSH6/PMS2) and MLH1 promoter methylation in primary endometrial carcinomas from 221 consecutive patients. Based on these results, tumors were categorized as sporadic or probable Lynch syndrome (PLS). Clinicopathologic variables and prognosis were compared according to MMR status and sporadic/PLS classification. Deficient MMR showed only trends towards favorable overall survival (OS) compared with intact MMR (p=0.13), whereas PLS showed significantly better OS than sporadic (p=0.038). Sporadic was significantly associated with older age, obesity, deep myometrial invasion, and advanced stage (p=0.008, 0.01, 0.02 and 0.03), while PLS was significantly associated with early stage and Lynch syndrome-associated multiple cancer (p=0.04 and 0.001). The trend towards favorable OS of PLS was stronger in advanced stage than in early stage (hazard ratio, 0.044 [95% CI 0-25.6] vs. 0.49 [0.063-3.8]). In the subset receiving adjuvant therapies, PLS showed trends towards favorable disease-free survival compared to sporadic by contrast with patients receiving no adjuvant therapies showing no such trend (hazard ratio, 0.045 [95% CI 0-20.3] vs. 0.81 [0.095-7.0]). The current findings suggest that analyzing MMR status and searching for Lynch syndrome may identify a subset of patients with favorable survival and high sensitivity to adjuvant therapies, providing novel and useful implications for formulating the precision medicine in endometrial carcinoma. Copyright © 2015 Elsevier Inc. All rights reserved.

Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer.

PubMed

Lu, Youzhu; Jing, Jingjing; Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Sun, Mingjun; Yuan, Yuan

2017-01-01

Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival.

A clinicopathologic review and obstetric outcome of uterine smooth muscle tumor of uncertain malignant potential (STUMP) in a single institution.

PubMed

Ha, Hyeong In; Choi, Min Chul; Heo, Jin Hyung; Kim, Kyoung Ah; Jung, Sang Geun; Park, Hyun; Joo, Won Duk; Song, Seung Hun; Kim, Tae Hoen; Lee, Chan

2018-06-05

The present study aimed to analyze the clinicopathologic features and treatment of uSTUMP in a single institution. In addition, we described the obstetric outcomes after uterine-preserving surgery for uSTUMP. A retrospective chart review was performed of patients diagnosed with uSTUMP between January 2000 and February 2018 at the Comprehensive Gynecologic Cancer Center, CHA Bundang Medical Center. We obtained data on the patients' demographics, treatment, therapeutic results, time to recurrence, disease-free and overall survival, and subsequent obstetric outcomes. The central pathology reviews were carried out by two pathologists specializing in gynecologic oncology. A total of 19 patients diagnosed with uSTUMP were identified and included in the study. The mean age at diagnosis was 41 years (range 28-49 years). Frozen sections were performed in 11 patients including five patients during surgery. Nine of the 19 patients (47.4%) were treated by hysterectomy and 10 patients were initially treated by myomectomy. The mean follow-up period was 47 months (range 6-209 months). Two patients (10.5%; 2/19) experienced recurrence. Although not defined as recurrence in the present study criteria, one patient had a secondary diagnosis of atypical leiomyoma one year after the initial diagnosis of uSTUMP. Seven patients requested uterine-preserving treatment, five of whom wanted to become pregnant. Three of them (3/5; 60%) successfully delivered live birth to full term by Cesarean section without complications such as abortion, preterm delivery or uterine rupture, and tumor recurrence. The present study describes the clinicopathologic data of uSTUMP patients. Our results suggest a uSTUMP recurrence of 10.5%, comparable to previous reports. Although there is a possibility of malignant recurrence, fertility-preserving management is worth attempting because of relatively low affected age with careful close follow-up. Copyright © 2018 Elsevier B.V. All rights reserved.

PIK3CA gene mutations in Northwest Chinese esophageal squamous cell carcinoma

PubMed Central

Liu, Shi-Yuan; Chen, Wei; Chughtai, Ehtesham Annait; Qiao, Zhe; Jiang, Jian-Tao; Li, Shao-Min; Zhang, Wei; Zhang, Jin

2017-01-01

AIM To evaluate PIK3CA gene mutational status in Northwest Chinese esophageal squamous cell carcinoma (ESCC) patients, and examine the associations of PIK3CA gene mutations with clinicopathological characteristics and clinical outcome. METHODS A total of 210 patients with ESCC who underwent curative resection were enrolled in this study. Pyrosequencing was applied to investigate mutations in exons 9 and 20 of PIK3CA gene in 210 Northwest Chinese ESCCs. The associations of PIK3CA gene mutations with clinicopathological characteristics and clinical outcome were examined. RESULTS PIK3CA gene mutations in exon 9 were detected in 48 cases (22.9%) of a non-biased database of 210 curatively resected Northwest Chinese ESCCs. PIK3CA gene mutations were not associated with sex, tobacco use, alcohol use, tumor location, stage, or local recurrence. When compared with wild-type PIK3CA gene cases, patients with PIK3CA gene mutations in exons 9 experienced significantly better disease-free survival and overall survival rates. CONCLUSION The results of this study suggest that PIK3CA gene mutations could act as a prognostic biomarker in Northwest Chinese ESCC patients. PMID:28465643

Hematologic and serum biochemical reference intervals for free-ranging common bottlenose dolphins (Tursiops truncatus) and variation in the distributions of clinicopathologic values related to geographic sampling site.

PubMed

Schwacke, Lori H; Hall, Ailsa J; Townsend, Forrest I; Wells, Randall S; Hansen, Larry J; Hohn, Aleta A; Bossart, Gregory D; Fair, Patricia A; Rowles, Teresa K

2009-08-01

To develop robust reference intervals for hematologic and serum biochemical variables by use of data derived from free-ranging bottlenose dolphins (Tursiops truncatus) and examine potential variation in distributions of clinicopathologic values related to sampling sites' geographic locations. 255 free-ranging bottlenose dolphins. Data from samples collected during multiple bottlenose dolphin capture-release projects conducted at 4 southeastern US coastal locations in 2000 through 2006 were combined to determine reference intervals for 52 clinicopathologic variables. A nonparametric bootstrap approach was applied to estimate 95th percentiles and associated 90% confidence intervals; the need for partitioning by length and sex classes was determined by testing for differences in estimated thresholds with a bootstrap method. When appropriate, quantile regression was used to determine continuous functions for 95th percentiles dependent on length. The proportion of out-of-range samples for all clinicopathologic measurements was examined for each geographic site, and multivariate ANOVA was applied to further explore variation in leukocyte subgroups. A need for partitioning by length and sex classes was indicated for many clinicopathologic variables. For each geographic site, few significant deviations from expected number of out-of-range samples were detected. Although mean leukocyte counts did not vary among sites, differences in the mean counts for leukocyte subgroups were identified. Although differences in the centrality of distributions for some variables were detected, the 95th percentiles estimated from the pooled data were robust and applicable across geographic sites. The derived reference intervals provide critical information for conducting bottlenose dolphin population health studies.

Differences in TGF-β1 signaling and clinicopathologic characteristics of histologic subtypes of gastric cancer.

PubMed

Pak, Kyung Ho; Kim, Dong Hoon; Kim, Hyunki; Lee, Do Hyung; Cheong, Jae-Ho

2016-02-04

Aberrant TGF-β1 signaling is suggested to be involved in gastric carcinogenesis. However, the role of TGF-β1 in intestinal-type [i-GC] and diffuse-type [d-GC] gastric cancer remains largely unknown. In this study, we evaluated the expression of TGF-β1 signaling molecules and compared the clinicopathological features of i-GC and d-GC. Patients (n=365, consecutive) who underwent curative gastrectomy for gastric adenocarcinoma in 2005 were enrolled. We performed immunohistochemical staining of TGF-β1, TGF-β1 receptor-2 (TβR2), Smad4, p-ERK1/2, TGF-activated kinase (TAK)1, and p-Akt in 68 paraffin-embedded tumor blocks (33 i-GC and 35 d-GC), scored the expression according to the extent of staining, and evaluated differences between the histologic subtypes. Patients with d-GC differed from those with i-GC as follows: younger and more likely to be female; more aggressive stage; higher recurrence rate. The expression of TGF-β1 and TβR2 was higher in i-GC (P = 0.05 and P <0.001, respectively). The expression of Smad4, a representative molecule of the Smad-dependent pathway, was decreased in both subtypes. TAK1 and p-Akt, two major molecules involved in the Smad-independent pathway, were over-expressed (69 ~87% of cases stained), without a statistically significant difference between i-GC and d-GC. Of note, the expression of p-ERK1/2, a Smad-independent pathway, was significantly increased in i-GC (P = 0.008). The clinicopathological characteristics vary in different histologic gastric cancer subtypes. Although TGF-β1 signaling in gastric cancer cells appears hyper-activated in i-GC compared to d-GC, the Smad-dependent pathway seems down-regulated while the Smad-independent pathway seems up-regulated in both histologic subtypes.

Prognostic Utility of the 21-Gene Assay in Hormone Receptor–Positive Operable Breast Cancer Compared With Classical Clinicopathologic Features

PubMed Central

Goldstein, Lori J.; Gray, Robert; Badve, Sunil; Childs, Barrett H.; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L.; Ravdin, Peter M.; Davidson, Nancy E.; Sledge, George W.; Perez, Edith A.; Shulman, Lawrence N.; Martino, Silvana; Sparano, Joseph A.

2008-01-01

Purpose Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. Patients and Methods A sample of 465 patients with hormone receptor (HR) –positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Results Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). Conclusion The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments. PMID:18678838

Prognostic utility of the 21-gene assay in hormone receptor-positive operable breast cancer compared with classical clinicopathologic features.

PubMed

Goldstein, Lori J; Gray, Robert; Badve, Sunil; Childs, Barrett H; Yoshizawa, Carl; Rowley, Steve; Shak, Steven; Baehner, Frederick L; Ravdin, Peter M; Davidson, Nancy E; Sledge, George W; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Sparano, Joseph A

2008-09-01

Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features. A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory. Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18). The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.

Perioperative and long-term outcome of intrahepatic cholangiocarcinoma involving the hepatic hilus after curative-intent resection: comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma.

PubMed

Zhang, Xu-Feng; Bagante, Fabio; Chen, Qinyu; Beal, Eliza W; Lv, Yi; Weiss, Matthew; Popescu, Irinel; Marques, Hugo P; Aldrighetti, Luca; Maithel, Shishir K; Pulitano, Carlo; Bauer, Todd W; Shen, Feng; Poultsides, George A; Soubrane, Olivier; Martel, Guillaume; Koerkamp, B Groot; Guglielmi, Alfredo; Itaru, Endo; Pawlik, Timothy M

2018-05-01

Intrahepatic cholangiocarcinoma with hepatic hilus involvement has been either classified as intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma. The present study aimed to investigate the clinicopathologic characteristics and short- and long-term outcomes after curative resection for hilar type intrahepatic cholangiocarcinoma in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma. A total of 912 patients with mass-forming peripheral intrahepatic cholangiocarcinoma, 101 patients with hilar type intrahepatic cholangiocarcinoma, and 159 patients with hilar cholangiocarcinoma undergoing curative resection from 2000 to 2015 were included from two multi-institutional databases. Clinicopathologic characteristics and short- and long-term outcomes were compared among the 3 groups. Patients with hilar type intrahepatic cholangiocarcinoma had more aggressive tumor characteristics (eg, higher frequency of vascular invasion and lymph nodes metastasis) and experienced more extensive resections in comparison with either peripheral intrahepatic cholangiocarcinoma or hilar cholangiocarcinoma patients. The odds of lymphadenectomy and R0 resection rate among patients with hilar type intrahepatic cholangiocarcinoma were comparable with hilar cholangiocarcinoma patients, but higher than peripheral intrahepatic cholangiocarcinoma patients (lymphadenectomy incidence, 85.1% vs 42.5%, P < .001; R0 rate, 75.2% vs 88.8%, P < .001). After curative surgery, patients with hilar type intrahepatic cholangiocarcinoma experienced a higher rate of technical-related complications compared with peripheral intrahepatic cholangiocarcinoma patients. Of note, hilar type intrahepatic cholangiocarcinoma was associated with worse disease-specific survival and recurrence-free survival after curative resection versus peripheral intrahepatic cholangiocarcinoma (median disease-specific survival, 26.0 vs 54.0 months, P < .001; median recurrence-free survival, 13.0 vs 18.0 months, P = .021) and hilar cholangiocarcinoma (median disease-specific survival, 26.0 vs 49.0 months, P = .003; median recurrence-free survival, 13.0 vs 33.4 months, P < .001). Mass-forming intrahepatic cholangiocarcinoma with hepatic hilus involvement is a more aggressive type of cholangiocarcinoma, which showed distinct clinicopathologic characteristics, worse long-term outcomes after curative resection, in comparison with peripheral intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma. Copyright © 2018 Elsevier Inc. All rights reserved.

The clinicopathological and prognostic value of long non-coding RNA ZEB1-AS1 in solid tumors: A meta-analysis.

PubMed

Liang, Chaojie; Liu, Jing; Ge, Hua; Xu, Yingchen; Li, Guangming; Wu, Jixiang

2018-05-17

Studies have reported that Zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is overexpressed in many malignant tumors. However, the sample size in those studies was limited, so the clinicopathological and prognostic value of ZEB1-AS1 in solid tumors remains undetermined, Accordingly, the aim of this meta-analysis was to evaluate the relationship between the expression of lncRNA ZEB1-AS1 and clinicopathological characteristics and prognosis in patients with solid tumors. Pooled odds ratios (ORs) and hazard ratios (HRs) were estimated with 95% confidence interval (CI) to assess the relation between ZEB1-AS1 and the clinicopathological characteristics and prognosis of patients with cancer. A total of 10 studies, comprising 861 patients, were included in this meta-analysis. The pooled results suggested that high ZEB1-AS1 expression was related to low differentiation (low vs. high + moderate: OR = 2.99, 95% CI = [2.03, 4.39]), increased lymph node metastasis (YES vs. NO: OR = 4.62, 95% CI = [2.90, 7.37]) and advanced TNM stage (I + II vs. III + IV: OR = 0.41, 95% CI = [0.23, 0.75]), but not to gender and tumor size. Moreover, high ZEB1-AS1 expression was associated with poor overall survival (OS; HR = 1.86, 95% CI = [1.57, 2.14]) and disease-free survival (DFS; HR = 2.03, 95% CI = [1.28, 2.77]). Thus, ZEB1-AS1 could be an independent predictive factor for OS (HR = 2.07, 95% CI = [1.57, 2.56]) in patients with cancers. High expression of ZEB1-AS1 was associated with advanced clinicopathological characteristics, and ZEB1-AS1overexpression may be a potential prognostic biomarker in human cancer. However, more studies involving various tumor types and large sample size are needed. Copyright © 2018 Elsevier B.V. All rights reserved.

Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.

PubMed

De Paz, Dante; Kao, Huang-Kai; Huang, Yenlin; Chang, Kai-Ping

2017-08-10

Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients. In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy. Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

Subsets of microsatellite-unstable colorectal cancers exhibit discordance between the CpG island methylator phenotype and MLH1 methylation status.

PubMed

Kim, Jung H; Rhee, Ye-Y; Bae, Jeong-M; Kwon, Hyeong-J; Cho, Nam-Y; Kim, Mi J; Kang, Gyeong H

2013-07-01

Although the presence of MLH1 methylation in microsatellite-unstable colorectal cancer generally indicates involvement of the CpG island methylator phenotype (CIMP) in the development of the tumor, these two conditions do not always correlate. A minority of microsatellite-unstable colorectal cancers exhibit discordance between CIMP and MLH1 methylation statuses. However, the clinicopathological features of such microsatellite-unstable colorectal cancers with discrepant MLH1 methylation and CIMP statuses remain poorly studied. Microsatellite-unstable colorectal cancers (n=220) were analyzed for CIMP and MLH1 methylation statuses using the MethyLight assay. Based on the combinatorial CIMP and MLH1 methylation statuses, the microsatellite-unstable colorectal cancers were grouped into four subtypes (CIMP-high (CIMP-H) MLH1 methylation-positive (MLH1m+), CIMP-H MLH1 methylation-negative, CIMP-low/0 (CIMP-L/0) MLH1m+, and CIMP-L/0 MLH1 methylation-negative), which were compared in terms of their associations with clinicopathological and molecular features. The CIMP-L/0 MLH1 methylation-negative and CIMP-H MLH1m+ subtypes were predominant, comprising 63.6 and 24.1% of total microsatellite-unstable colorectal cancers, respectively. The discordant subtypes, CIMP-H MLH1 methylation-negative and CIMP-L/0 MLH1m+, were found in 5 and 7% of microsatellite-unstable colorectal cancers, respectively. The CIMP-H MLH1 methylation-negative subtype exhibited elevated incidence rates in male patients and was associated with larger tumor size, more frequent loss of MSH2 expression, increased frequency of KRAS mutation, and advanced cancer stage. The CIMP-L/0 MLH1m+ subtype was associated with onset at an earlier age, a predominance of MLH1 loss, and earlier cancer stage. None of the CIMP-L/0 MLH1m+ subtype patients succumbed to death during the follow-up. Our findings suggest that the discordant subtypes of colorectal cancers exhibit distinct clinicopathological and molecular features, although the proportion of discordant subtypes is low. The microsatellite-unstable colorectal cancers of the same CIMP status tended to exhibit different clinicopathological features depending on MLH1 methylation status.

Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review

PubMed Central

2014-01-01

Background KRAS mutations in codons 12 and 13 are established predictive biomarkers for anti-EGFR therapy in colorectal cancer. Previous studies suggest that KRAS codon 61 and 146 mutations may also predict resistance to anti-EGFR therapy in colorectal cancer. However, clinicopathological, molecular, and prognostic features of colorectal carcinoma with KRAS codon 61 or 146 mutation remain unclear. Methods We utilized a molecular pathological epidemiology database of 1267 colon and rectal cancers in the Nurse’s Health Study and the Health Professionals Follow-up Study. We examined KRAS mutations in codons 12, 13, 61 and 146 (assessed by pyrosequencing), in relation to clinicopathological features, and tumor molecular markers, including BRAF and PIK3CA mutations, CpG island methylator phenotype (CIMP), LINE-1 methylation, and microsatellite instability (MSI). Survival analyses were performed in 1067 BRAF-wild-type cancers to avoid confounding by BRAF mutation. Cox proportional hazards models were used to compute mortality hazard ratio, adjusting for potential confounders, including disease stage, PIK3CA mutation, CIMP, LINE-1 hypomethylation, and MSI. Results KRAS codon 61 mutations were detected in 19 cases (1.5%), and codon 146 mutations in 40 cases (3.2%). Overall KRAS mutation prevalence in colorectal cancers was 40% (=505/1267). Of interest, compared to KRAS-wild-type, overall, KRAS-mutated cancers more frequently exhibited cecal location (24% vs. 12% in KRAS-wild-type; P < 0.0001), CIMP-low (49% vs. 32% in KRAS-wild-type; P < 0.0001), and PIK3CA mutations (24% vs. 11% in KRAS-wild-type; P < 0.0001). These trends were evident irrespective of mutated codon, though statistical power was limited for codon 61 mutants. Neither KRAS codon 61 nor codon 146 mutation was significantly associated with clinical outcome or prognosis in univariate or multivariate analysis [colorectal cancer-specific mortality hazard ratio (HR) = 0.81, 95% confidence interval (CI) = 0.29-2.26 for codon 61 mutation; colorectal cancer-specific mortality HR = 0.86, 95% CI = 0.42-1.78 for codon 146 mutation]. Conclusions Tumors with KRAS mutations in codons 61 and 146 account for an appreciable proportion (approximately 5%) of colorectal cancers, and their clinicopathological and molecular features appear generally similar to KRAS codon 12 or 13 mutated cancers. To further assess clinical utility of KRAS codon 61 and 146 testing, large-scale trials are warranted. PMID:24885062

Decreased expression of hsa_circ_0137287 predicts aggressive clinicopathologic characteristics in papillary thyroid carcinoma.

PubMed

Lan, Xiabin; Cao, Jun; Xu, Jiajie; Chen, Chao; Zheng, Chuanming; Wang, Jiafeng; Zhu, Xuhang; Zhu, Xin; Ge, Minghua

2018-05-22

Circular RNA (circRNA) is a new type of noncoding RNA that can serve as ideal biomarkers. Evidence has showed that circRNAs play an important role in carcinogenesis and cancer development. However, little is known about the diagnostic value of circRNAs in papillary thyroid carcinoma (PTC) as well as their associations with clinicopathologic characteristics of patients with PTC. The expression levels of hsa_circ_0137287 were detected in 120 PTC and 60 adjacent noncancerous thyroid tissues by quantitative real-time polymerase chain reaction. The relationships between the expression of hsa_circ_0137287 in PTC and the clinicopathologic factors were analyzed. Finally, receiver operating characteristic (ROC) curves were generated to assess the diagnostic value of hsa_circ_0137287 as a biomarker for PTC. The expression of hsa_circ_0137287 was significantly downregulated in PTC tissues compared with adjacent noncancerous tissues (P < .0001). Downregulation of hsa_circ_0137287 correlated with aggressive clinicopathologic characteristics of PTC such as extrathyroidal extension (P < .001), lymph node metastasis (P = .022), advanced T stage (P < .001) and larger tumor size (P < .001). The ROC curves revealed that hsa_circ_0137287 had a potential diagnostic value in predicting malignancy, extrathyroidal extension and lymph node metastasis. The area under curves were 0.8973 (95% CI = 0.8452-0.9494, P < .0001), 0.6885 (95%CI = 0.5908-0.7862, P = .0009), and 0.6691(95%CI = 0.5641-0.7742, P = .0034), respectively. Our findings suggest that hsa_circ_0137287 may serve as a novel biomarker for PTC. © 2018 Wiley Periodicals, Inc.

Clinicopathological analysis of the age-related differences in patients with Epstein-Barr virus (EBV)-associated extranasal natural killer (NK)/T-cell lymphoma with reference to the relationship with aggressive NK cell leukaemia and chronic active EBV infection-associated lymphoproliferative disorders.

PubMed

Takahashi, Emiko; Ohshima, Koichi; Kimura, Hiroshi; Hara, Kazuo; Suzuki, Ritsuro; Kawa, Keisei; Eimoto, Tadaaki; Nakamura, Shigeo

2011-10-01

Extranodal natural killer (NK)/T-cell lymphoma (NKTL), comprising nasal NKTL and extranasal NKTL (ENKTL), is associated with Epstein-Barr virus (EBV). A bimodal age distribution was noted in NKTL patients. We examined the clinicopathological differences between two age groups of ENKTL patients (n = 23) and compared the findings with those of aggressive NK cell leukaemia (ANKL; n = 10) and monoclonal chronic active EBV infection-associated T/NK-cell lymphoproliferative disorders [chronic active EBV infection/TNK-lymphoproliferative disorders (CAEBV/TNK-LPD)] of NK-cell type (n = 45). Distinct differences existed between elderly (> 50 years; n = 13) and younger (≤ 50 years; n = 10) ENKTL patients; the latter showed a higher disease stage (P = 0.0286), worse performance status (P = 0.0244), more frequent B symptoms (P = 0.0286) and more frequent liver, spleen and bone marrow involvement (P = 0.0222, 0.0005 and 0.0259, respectively). Few clinicopathological differences existed between younger ENKTL and ANKL patients. Patients with monoclonal CAEBV/TNK-LPD of NK-cell type (n = 45) showed features similar to those in younger ENKTL/ANKL patients, except a more juvenile onset of CAEBV-related symptoms and better prognosis. However, the onset age of overt leukaemia/lymphoma in CAEBV/TNK-LPD patients and overall survival thereafter were similar to those in younger ENKTL/ANKL patients. ENKTL (≤ 50 years) is distinct from that in elderly patients and may encompass ANKL and overlap in the clinicopathological profile with NK-cell type CAEBV/TNK-LPD. 2011 Blackwell Publishing Limited.

Association of prostate cancer risk variants with clinicopathologic characteristics of the disease

PubMed Central

Xu, Jianfeng; Isaacs, Sarah D.; Sun, Jielin; Li, Ge; Wiley, Kathleen E.; Zhu, Yi; Hsu, Fang-Chi; Wiklund, Fredrik; Turner, Aubrey R.; Adams, Tamara S.; Liu, Wennuan; Trock, Bruce J.; Partin, Alan W.; Chang, Baoli; Walsh, Patrick C.; Grönberg, Henrik; Isaacs, William; Zheng, Siqun

2009-01-01

Purpose Fifteen independent genetic variants have been implicated in prostate cancer risk by recent genome-wide association studies. However, their association with clinicopathologic features of prostate cancer is uncertain. Experimental Design We systematically evaluated these 15 variants in 1,563 prostate cancer patients undergoing radical prostatectomy, taking advantage of the uniform tumor stage and grade information available for each of these cases. Associations of these variants with aggressiveness, pathologic Gleason scores, pathologic stage, age at diagnosis, or serum PSA levels were tested. Results After adjusting for multiple testing, none of the SNPs was individually or cumulatively associated with aggressiveness or individual clinicopathologic variables of prostate cancer such as Gleason scores, pathologic stage, or age at diagnosis of prostate cancer. The reported risk allele (G) for SNP rs2735839 in the KLK3 gene at 19q13 was more frequent in less aggressive prostate cancer patients (0.89) than in more aggressive prostate cancer patients (0.86), nominal P = 0.03, or in controls (0.86), nominal P = 0.04. Considering that this allele was also significantly associated with higher serum PSA levels among controls (nominal P = 0.003), the observed trend of higher frequency of this risk allele between less and more aggressive prostate cancer, or between less aggressive and controls may be due to detection bias of PSA screening. Conclusions Prostate cancer risk variants recently discovered from genome-wide case-control association studies are not associated with clinicopathologic variables in this population. Case-case studies are urgently needed in order to discover genetic variants that predict tumor aggressiveness. PMID:18794092

Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication of MTHFR rs1801133 and ATIC rs4673993 Polymorphisms

PubMed Central

Lima, Aurea; Monteiro, Joaquim; Bernardes, Miguel; Sousa, Hugo; Azevedo, Rita; Seabra, Vitor; Medeiros, Rui

2014-01-01

Objective. Methotrexate (MTX), the most used drug in rheumatoid arthritis (RA) treatment, showing variability in clinical response, is often associated with genetic polymorphisms. This study aimed to elucidate the role of methylenetetrahydrofolate reductase (MTHFR) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients. Methods. Study included 233 RA patients treated with MTX for at least six months. MTHFR C677T and ATIC T675C polymorphisms were genotyped and clinicopathological variables were collected. Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables. Results. Multivariate analyses demonstrated that MTHFR 677TT (OR = 4.63; P = 0.013) and ATIC 675T carriers (OR = 5.16; P = 0.013) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98; P = 0.001), patients positive to anti-cyclic citrullinated peptide (OR = 3.53; P = 0.004) and antinuclear antibodies (OR = 2.28; P = 0.045), with higher health assessment questionnaire score (OR = 2.42; P = 0.007), and nonsteroidal anti-inflammatory drug users (OR = 2.77; P = 0.018) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11; P < 0.001) was associated with response. Conclusion. Our study suggests that MTHFR C677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment. PMID:24967362

The Clinicopathological Significance of MicroRNA-155 in Breast Cancer: A Meta-Analysis

PubMed Central

Zeng, Hui; Fang, Cheng; Nam, Seungyoon; Cai, Qing; Long, Xinghua

2014-01-01

Objective. Previous studies demonstrated that the associations between expression level of microRNA-155 (miR-155) and clinicopathological significance of breast cancer remained inconsistent. Therefore, we performed a meta-analysis based on eligible studies to summarize the possible associations. Methods. We identified eligible studies published up to May 2014 by a comprehensive search of PubMed, EMBASE, CNKI, and VIP databases. The analysis was performed with RevMan. 5.0 software. Results. A total of 15 studies were included. The results of meta-analysis showed that miR-155 was positively correlated with breast cancer with standardized mean difference (SMD) = 1.22. Elevated miR-155 was found in Her-2 positive or lymph node metastasis positive, or p53 mutant type breast cancer. But the result showed to be insignificant in TNM comparison. With respect to estrogen receptor alpha (ER) and progesterone receptor (PR) status, both of them showed significant associations with SMD = −1.2 and −1.85, respectively. Conclusion. MiR-155 detection might have a diagnostic value in breast cancer patients. It might be used as an auxiliary biomarker for different clinicopathological breast cancer. PMID:25157366

The Effect of Naturally Occurring Chronic Kidney Disease on the Micro-Structural and Mechanical Properties of Bone

PubMed Central

Meltzer, Hagar; Milrad, Moran; Brenner, Ori; Atkins, Ayelet; Shahar, Ron

2014-01-01

Chronic kidney disease (CKD) is a growing public health concern worldwide, and is associated with marked increase of bone fragility. Previous studies assessing the effect of CKD on bone quality were based on biopsies from human patients or on laboratory animal models. Such studies provide information of limited relevance due to the small size of the samples (biopsies) or the non-physiologic CKD syndrome studied (rodent models with artificially induced CKD). Furthermore, the type, architecture, structure and biology of the bone of rodents are remarkably different from human bones; therefore similar clinicopathologic circumstances may affect their bones differently. We describe the effects of naturally occurring CKD with features resembling human CKD on the skeleton of cats, whose bone biology, structure and composition are remarkably similar to those of humans. We show that CKD causes significant increase of resorption cavity density compared with healthy controls, as well as significantly lower cortical mineral density, cortical cross-sectional area and cortical cross-sectional thickness. Young's modulus, yield stress, and ultimate stress of the cortical bone material were all significantly decreased in the skeleton of CKD cats. Cancellous bone was also affected, having significantly lower trabecular thickness and bone volume over total volume in CKD cats compared with controls. This study shows that naturally occurring CKD has deleterious effects on bone quality and strength. Since many similarities exist between human and feline CKD patients, including the clinicopathologic features of the syndrome and bone microarchitecture and biology, these results contribute to better understanding of bone abnormalities associated with CKD. PMID:25333360

Clinicopathological and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) overexpression in colorectal cancer: a meta-analysis

PubMed Central

Zhao, Yang; Dai, Cong; Wang, Meng; Kang, Huafeng; Lin, Shuai; Yang, Pengtao; Liu, Xinghan; Liu, Kang; Xu, Peng; Zheng, Yi; Li, Shanli; Dai, Zhijun

2016-01-01

Metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and the increasing amount of evidences suggest that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in colorectal cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of MACC1 overexpression on clinicopathological features and survival outcomes in colorectal cancer. PubMed, CNKI, and Wanfang databases were searched for relevant articles published update to December 2015. Correlation of MACC1 expression level with overall survival (OS), disease-free survival (DFS), and clinicopathological features were analyzed. In this meta-analysis, fifteen studies with a total of 2,161 colorectal cancer patients were included. Our results showed that MACC1 overexpression was significantly associated with poorer OS and DFS. Moreover, MACC1 overexpression was significantly associated with gender, localization, TNM stage, T stage, and N stage. Together, our meta-analysis showed that MACC1 overexpression was significantly associated with poor survival rates, regional invasion and lymph-node metastasis. MACC1 expression level can serve as a novel prognostic factor in colorectal cancer patients. PMID:27542234

Relationship between ABO blood group and clinicopathological factors and their effect on the survival of Japanese patients with esophageal squamous cell carcinoma.

PubMed

Shiratori, Fumiaki; Shimada, Hideaki; Yajima, Satoshi; Suzuki, Takashi; Oshima, Yoko; Nanami, Tatsuki; Ito, Masaaki; Kaneko, Hironori

2017-08-01

Several studies have evaluated the association between ABO blood group and the prognosis of various types of cancer; however, little is known about the relationship between ABO blood group and esophageal squamous cell carcinoma (SCC). We investigated how ABO blood group and clinicopathological characteristics are related to the survival of Japanese patients with esophageal SCC. We reviewed the medical records of 181 patients who underwent surgery for esophageal SCC between June, 2004 and December, 2015 and analyzed the association between ABO blood group and clinicopathological factors. Clinicopathological factors were also evaluated by univariate and multivariate analyses for possible association with survival. The prevalence of each blood group was as follows: A, 35.5%; B, 22.4%; O, 32.8%; and AB, 8.2%. The 5-year overall survival of all patients was 37.1%. Patients with non-type B blood had significantly worse 5-year overall survival than those with type B blood (30.2 vs. 58.8%, P < 0.05). ABO blood groups were associated with the survival of Japanese patients with esophageal SCC. Patients with non-B blood groups had significantly worse overall survival than those with the B blood group.

Clinicopathologic and prognostic implications of progranulin in breast carcinoma.

PubMed

Li, Li-qin; Huang, Hui-lian; Ping, Jin-liang; Wang, Xiao-hong; Zhong, Jing; Dai, Li-cheng

2011-07-05

Progranulin is a newly discovered 88-kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC. Its expression is closely correlated with the development and metastasis of several cancers. However, no immunohistochemical evidence currently exists to correlate progranulin expression with clinicopathologic features in breast carcinoma biopsies, and the role of progranulin as a new marker of metastatic risk and prognosis in breast cancer has not yet been studied. The aim of this study was to investigate the clinicopathologic and prognostic implications of progranulin expression in breast carcinoma and its correlation with tumor angiogenesis. Progranulin expression was determined immunohistochemically in 183 surgical specimens from patients with breast cancer and 20 tissue samples from breast fibroadenomas. The tumor angiogenesis-related biomarker, vascular endothelial growth factor was assayed and microvessel density was assessed by counting vascular endothelial cells in tumor tissues labeled with endoglin antibody. The relationship between progranulin expression and the clinicopathologic data were analyzed. Progranulin proteins were overexpressed in breast cancer. The level of progranulin expression was significantly correlated with tumor size (P = 0.004), lymph node metastasis (P < 0.001) and TNM staging (P < 0.001). High progranulin expression was associated with higher tumor angiogenesis, reflected by increased vascular endothelial growth factor expression (P < 0.001) and higher microvessel density (P = 0.002). Progranulin may be a valuable marker for assessing the metastasis and prognosis of breast cancer, and could provide the basis for new combination regimens with antiangiogenic activity.

Surgical pathology of epilepsy-associated non-neoplastic cerebral lesions: a brief introduction with special reference to hippocampal sclerosis and focal cortical dysplasia

PubMed Central

Miyata, Hajime; Hori, Tomokatsu; Vinters, Harry V.

2014-01-01

Among epilepsy-associated non-neoplastic lesions, mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) and malformation of cortical development (MCD) including focal cortical dysplasia (FCD), are the two most frequent causes of drug-resistant focal epilepsies constituting about 50% of all surgical pathology of epilepsy. Several distinct histological patterns have been historically recognized in both HS and FCD, and several studies have tried to perform clinicopathological correlation; results, however, have been controversial, particularly in terms of postsurgical seizure outcome. Recently, the International League Against Epilepsy constituted a Task Forces of Neuropathology and FCD within the Commission on Diagnostic Methods, to establish an international consensus of histological classification of HS and FCD, respectively, based on agreement with the recognition of the importance of defining a histopathological classification system that reliably has some clinicopathological correlation. Such consensus classifications are likely to facilitate future clinicopathological study. Meanwhile, we reviewed neuropathology of 41 surgical cases of mTLE, and confirmed three type/patterns of HS along with no HS, based on the qualitative evaluation of the distribution and severity of neuronal loss and gliosis within hippocampal formation; i.e., HS type 1 (61%) equivalent to ‘classical’ Ammon’s horn sclerosis, HS type 2 (2%) representing CA1 sclerosis, HS type 3 (17%) equivalent to end folium sclerosis, and no HS (19%). Furthermore we performed a neuropathological comparative study on mTLE-HS and dementia associated HS (d-HS) in elderly, and confirmed that neuropathological features differ between mTLE-HS and d-HS in the distribution of hippocampal neuronal loss and gliosis, morphology of reactive astrocytes and their protein expression, and presence of concomitant neurodegenerative changes particularly Alzheimer type and TDP-43 pathologies. These differences may account, at least in part, for the difference in pathogenesis and epileptogenicity of HS in mTLE and senile dementia. However, the etiology and pathogenesis of most epileptogenic lesions are yet to be elucidated. PMID:23530853

Gastric cancer in young vs old Romanian patients: immunoprofile with emphasis on maspin and mena protein reactivity.

PubMed

Gurzu, Simona; Kadar, Zoltan; Sugimura, Haruhiko; Bara, Tivadar; Bara, Tivadar; Halmaciu, Ioana; Jung, Ioan

2015-03-01

Increasing number of early-onset gastric carcinomas (GCs) and controversial results regarding the differences among young and older patients with this type of cancer are the reasons why correlation of clinicopathological factors with molecular markers is necessary. The aim of our study was to compare the demographic, clinical and immunohistochemical (IHC) aspects in Romanian patients with GC diagnosed below and above 45 years old. In 191 samples provided from patients with GC, the clinicopathological parameters were correlated with a panel of 15 antibodies: E-cadherin, HER-2, VEGF, CD31, CD105, COX-2, maspin, bax, bcl-2, p53, Ki67, MLH-1, MSH-2, mena protein and vimentin. Compared to the conventional cases, GCs diagnosed below 45 years old were more frequently located at the gastroesophageal junction and presented a higher percentage of lymph node metastases. The diffuse type E-cadherin/mena/p53/Ki67/bax-negative cases that displayed nuclear maspin positivity were also more frequently in younger patients. The intestinal type early-onset GCs were the most angiogenic ones, the apoptotic rate being lower than in the intestinal type GCs of the aged. Compared to the conventional cases, in the early-onset GCs the nuclear maspin-mediated antiproliferative activity is more intense in diffuse type while the mena-dependent tumor cell proliferation is more characteristic for intestinal type GCs. © 2014 APMIS. Published by John Wiley & Sons Ltd.

Clinicopathological and prognostic significance of cyclin D1 amplification in patients with breast cancer: a meta-analysis.

PubMed

He, Qi; Wu, Jingxun; Liu, Xin-Li; Ma, Yi-Han; Wu, Xiao-Ting; Wang, Wen-Yi; An, Han-Xiang

2017-01-01

Cyclin D1 plays a critical role in tumorigenesis and the regulation of the G1/S transition in the cell cycle. The relationship between cyclin D1 amplification and clinicopathological parameters in patients with breast cancer remains controversial and its impact on survival outcome is not completely clear. We conducted a meta-analysis to investigate the associations between cyclin D1 gene amplification and certain clinicopathological characteristics and the prognosis in breast cancer. Literature search of PubMed (up to August 3, 2016) was performed. We used Stata 12.0 (Stata Corporation, Texas, US) to analyze the correlations between cyclin D1 amplification and clinicopathological features and the prognostic indicator relapse free survival (RFS) and overall survival (OS) in patients with breast cancer. Publication bias analysis and sensitivity analysis were performed. A total of 9,238 breast cancer patients from 21 studies were included. The pooled odds ratios (ORs) indicated that cyclin D1 amplification was significantly associated with estrogen receptor (ER), progesterone receptor (PR), histological grade and lymph node status, but not associated with human epidermal growth factor receptor-2 (HER2) and tumor size. The combined hazard ratios (HRs) for RFS and OS showed that patients with cyclin D1 amplification displayed a 1.31-fold higher risk of recurrence (HR =1.31, 95% confidence interval (95% CI):1.02-1.60, p<0.01), and a risk of mortality 1.22-fold higher times greater than those without cyclin D1 amplification (HR=1.22, 95% CI:0.99- 1.44, p<0.01), respectively. Our meta-analysis indicated that cyclin D1 amplification is significantly associated with established clinicopathological variables and can be used as a poor prognostic indicator for patients with breast cancer.

Nottingham Clinico-Pathological Response Index (NPRI) after neoadjuvant chemotherapy (Neo-ACT) accurately predicts clinical outcome in locally advanced breast cancer.

PubMed

Abdel-Fatah, Tarek M; Ball, Graham; Lee, Andrew H S; Pinder, Sarah; MacMilan, R Douglas; Cornford, Eleanor; Moseley, Paul M; Silverman, Rafael; Price, James; Latham, Bruce; Palmer, David; Chan, Arlene; Ellis, Ian O; Chan, Stephen Y T

2015-03-01

There is a need to identify more sensitive clinicopathologic criteria to assess the response to neoadjuvant chemotherapy (Neo-ACT) and guide subsequent adjuvant therapy. We performed a clinicopathologic assessment of 426 patients who had completed Neo-ACT for locally advanced breast cancer (LABC) with a median follow-up of 70 months. Patients were divided into a training set treated with anthracycline combination chemotherapy (n = 172); an internal validation set treated with anthracycline and taxane (n = 129); and an external validation set treated with anthracycline with or without taxane (n = 125). A multivariate Cox regression model demonstrated the absence of fibrosis, presence of lymphovascular invasion, increasing number of lymph node metastases, and administration of hormone therapy were significantly associated with short breast cancer-specific survival (BCSS) and disease-free survival (DFS); Ps < 0.01, while reduction of tumor size was associated with DFS (P = 0.022). Nottingham Clinico-Pathological Response Indexes (NPRI) were calculated, and four prognostic groups (NPRI-PG) were identified. Patients in prognostic group 2 (NPRI-PG2) for BCSS (66 of 172; 38.4%) have the same prognosis as those who achieved pathologic complete response (pCR; NPRI-PG1; 15%). Receiver-operating characteristic (ROC) curves indicated that the NPRI outperformed the currently used prognostic factors and adding the NPRI improved their performance as a predictor for both BCSS (area under the curve [AUC], 0.88) and DFS (AUC, 0.87). The NPRI predicts BCSS and DFS, with a higher sensitivity than pCR. The NPRI can also improve the sensitivity and specificity of clinicopathologic response as a study endpoint, for assessing response to Neo-ACT, and can serve as a valuable tool for the discovery of future predictive molecular markers. ©2014 American Association for Cancer Research.

Clinicopathological Characteristics of Patients with Non-Small-Cell Lung Cancer Who Harbor EML4-ALK Fusion Gene: A Meta-Analysis

PubMed Central

Zhao, Fengzhi; Xu, Meng; Lei, Honcho; Zhou, Ziqi; Wang, Liang; Li, Ping; Zhao, Jianfu; Hu, Penghui

2015-01-01

Background A novel fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has been recently identified in non-small-cell lung cancers (NSCLCs). Patients with the EML4-ALK fusion gene demonstrate unique clinicopathological and physiological characteristics. Here we present a meta-analysis of large-scale studies to evaluate the clinicopathological characteristics of NSCLC patients harboring the EML4-ALK fusion gene. Methods Both English and Chinese databases were systematically used to search the materials of the clinicopathological characteristics of patients with NSCLC harboring the EML4-ALK fusion gene. Pooled relative risk (RR) estimates and the 95% confidence intervals (95% CI) were calculated with the fixed or random effect model. Publication bias and chi-square test were also calculated. Results 27 retrospective studies were included in our meta-analysis. These studies included a total of 6950 patients. The incidence rate of EML4-ALK fusion in NSCLC patients was found to be 6.8% (472/6950). The correlation of the EML4-ALK fusion gene and clinicopathological characteristics of NSCLC patients demonstrated a significant difference in smoking status, histological types, stage, and ethnic characteristics. The positive rate of the EML4-ALK fusion gene expression in females were slightly higher than that in males, but not significantly (P = 0.52). In addition, the EML4-ALK fusion gene was mutually exclusive of the EGFR and KRAS mutation genes (P = 0.00). Conclusion Our pooled analysis revealed that the EML4-ALK fusion gene was observed predominantly in adenocarcinoma, non-smoking and NSCLC patients, especially those diagnosed in the advanced clinical stage of NSCLC. Additionally, the EML4-ALK fusion gene was exclusive of the EGFR and KRAS mutation genes. We surmise that IHC assay is a valuable tool for the prescreening of patients with ALK fusion gene in clinical practice, and FISH assay can be performed as a confirmation method. These insights might be helpful in guiding the appropriate molecular target therapy for NSCLC. PMID:25706305

Clinicopathological characteristics of patients with non-small-cell lung cancer who harbor EML4-ALK fusion gene: a meta-analysis.

PubMed

Zhao, Fengzhi; Xu, Meng; Lei, Honcho; Zhou, Ziqi; Wang, Liang; Li, Ping; Zhao, Jianfu; Hu, Penghui

2015-01-01

A novel fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has been recently identified in non-small-cell lung cancers (NSCLCs). Patients with the EML4-ALK fusion gene demonstrate unique clinicopathological and physiological characteristics. Here we present a meta-analysis of large-scale studies to evaluate the clinicopathological characteristics of NSCLC patients harboring the EML4-ALK fusion gene. Both English and Chinese databases were systematically used to search the materials of the clinicopathological characteristics of patients with NSCLC harboring the EML4-ALK fusion gene. Pooled relative risk (RR) estimates and the 95% confidence intervals (95% CI) were calculated with the fixed or random effect model. Publication bias and chi-square test were also calculated. 27 retrospective studies were included in our meta-analysis. These studies included a total of 6950 patients. The incidence rate of EML4-ALK fusion in NSCLC patients was found to be 6.8% (472/6950). The correlation of the EML4-ALK fusion gene and clinicopathological characteristics of NSCLC patients demonstrated a significant difference in smoking status, histological types, stage, and ethnic characteristics. The positive rate of the EML4-ALK fusion gene expression in females were slightly higher than that in males, but not significantly (P = 0.52). In addition, the EML4-ALK fusion gene was mutually exclusive of the EGFR and KRAS mutation genes (P = 0.00). Our pooled analysis revealed that the EML4-ALK fusion gene was observed predominantly in adenocarcinoma, non-smoking and NSCLC patients, especially those diagnosed in the advanced clinical stage of NSCLC. Additionally, the EML4-ALK fusion gene was exclusive of the EGFR and KRAS mutation genes. We surmise that IHC assay is a valuable tool for the prescreening of patients with ALK fusion gene in clinical practice, and FISH assay can be performed as a confirmation method. These insights might be helpful in guiding the appropriate molecular target therapy for NSCLC.

Expression and clinical significance of survivin in ovarian cancer: A meta-analysis.

PubMed

He, Xiaoyan; Yang, Kehu; Wang, Hailin; Chen, Xiaohong; Wu, Huifang; Yao, Liang; Ma, Shouye

2018-01-01

To assess the clinicopathological significance of survivin in ovarian carcinoma through this meta-analysis. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were searched for relevant studies published through September, 2017. Included studies reported the case-control study of surviving expression with ovarian cancer and its clinicopathological characteristics. The quality assessment was performed according to the Newcastle-Ottawa Scale (NOS) for quality assessment of case-control studies. Statistical analysis was performed with the software Stata 12.0. Twelve eligible studies with a total of 1097 patients were included in this meta-analysis. Survivin overexpression was closely related to FIGO stage (I-II vs. III-IV) of ovarian carcinoma (odds ratio [OR] = 0.26,95% confidence interval [CI]:0.16,0.42),P<0.00001),tumor grade (G1-G2 vs. G3) (OR = 0.29,95%CI(0.17, 0.51),P <0.0001), but was not significantly associated with lymphatic metastasis (OR = 1.53, 95%CI(0.77, 3.03, P = 0.23),ascites (OR = 0.89,95%CI(0.39,2.05),P = 0.79). Our meta-analysis shows that survivin is strongly associated with FIGO stage and tumor grade of ovarian carcinoma. Maybe survivin is a novel clinicopathological marker of ovarian carcinoma.

Comparison of Clinicopathological Characteristics in the Patients with Cardiac Cancer with or without Esophagogastric Junctional Invasion: A Single-Center Retrospective Cohort Study

PubMed Central

Ito, Hiroaki; Inoue, Haruhiro; Odaka, Noriko; Satodate, Hitoshi; Suzuki, Michitaka; Mukai, Shumpei; Takehara, Yusuke; Omoto, Tomokatsu; Kudo, Shin-ei

2013-01-01

Background. This study addresses clinicopathological differences between patients with gastric cardia and subcardial cancer with and without esophagogastric junctional invasion. Methods. We performed a single-center, retrospective cohort study. We studied patients who underwent curative surgery for gastric cardia and subcardial cancers. Tumors centered in the proximal 5 cm of the stomach were classed into two types, according to whether they did (Ge) or did not (G) invade the esophagogastric junction. Results. A total of 80 patients were studied; 19 (73.1%) of 26 Ge tumors and 16 (29.6%) of 54 G tumors had lymph nodes metastases. Incidence of nodal metastasis in pT1 tumors was significantly higher in the Ge tumor group. No nodal metastasis in cervical lymph nodes was recognized. Only two patients with Ge tumors had mediastinal lymph node metastases. Incidence of perigastric lymph node metastasis was significantly higher in those with Ge tumors. Ge tumors tended to be staged as progressive disease using the esophageal cancer staging manual rather than the gastric cancer staging manual. Conclusion. Because there are some differences in clinicopathological characteristics, it is thought to be adequate to distinguish type Ge from type G tumor. PMID:23365732

The challenge of diagnosing a malignancy metastatic to the ovary: clinicopathological characteristics vary and morphology can be different from that of the corresponding primary tumor.

PubMed

Lobo, João; Machado, Bianca; Vieira, Renata; Bartosch, Carla

2017-01-01

An accurate diagnosis of metastases to the ovary is essential for adequate patient management. The aim of this retrospective study was to characterize clinicopathological features of metastatic malignancies that presented as an ovarian mass and compare them with their corresponding primary tumors. We reviewed clinical files and histological material of 120 patients with metastases to the ovary, diagnosed in our center between 2000 and 2014. Metastases were diagnosed before (18 %), synchronously (33 %), or after (49 %) the primary tumor was identified; 25 % were single, 40 % were unilateral; 47 % were ≥13 cm. Most originated from the gastrointestinal tract (73 %), followed by breast (13 %), and female reproductive organs (10 %). Gross features varied with primary tumor site. Metastases from gastrointestinal malignancies were significantly larger and frequently showed necrosis. Metastases to the appendix were cystic (94 %), and almost all metastases to the stomach (96 %) and breast (87 %) were solid. The predominant histological pattern was discordant in 44 % cases, mostly due to cystic changes in ovarian metastases which were observed across several histological types. Other metastases showed a predominant histological pattern which was present only focally in the primary tumor. Metastases showed significantly more edema, necrosis, and hemorrhage, but less lymphovascular invasion and inflammatory infiltrate than the corresponding primary tumors. Metastases to the ovary present highly variable clinicopathological features which frequently differ from those of the corresponding primary tumor. A metastasis should always be considered in the differential diagnosis of an ovarian mass. All clinical, imaging, macroscopic, and histological aspects must be taken into account to establish a correct diagnosis which is essential for adequate treatment.

Epidemiological, Clinicopathological and Virological Features of Merkel Cell Carcinomas in Medical Center of University of Pécs, Hungary (2007-2012).

PubMed

Horváth, Katalin Barbara; Pankovics, Péter; Kálmán, Endre; Kádár, Zsolt; Battyáni, Zita; Lengyel, Zsuzsanna; Reuter, Gábor

2016-01-01

Merkel cell carcinoma (MCC) is a rare, highly aggressive skin tumour. In 2008, a Merkel cell polyomavirus (MC) was identified in MCCs as a potential etiological factor of MCC. The aims of this retrospective study were to investigate the epidemiological, clinicopathological and virological features of MCCs. Between 2007 and 2012, 11 patients had been diagnosed with MCC by histological methods in University of Pécs, Hungary. In eight MCC cases MC was tested by PCR (in primary skin lesions, lymph nodes/cutan metastases, MCC neighboring carcinomas). Clinicopathological characteristics (age, histological pattern, lymphovascular invasion, co-morbidities) of MC-positive and MC-negative cases were compared. MC was detected in three (37.5%) out of eight patients' primary tumour or metastasis. The average age was 73.8 (64.3 in MC-positive group). Except the youngest, 55 year-old patient (the primary tumour appeared on his leg), all tumours were found at the head and neck region. Immunosuppression (steroid therapy, chronic lymphoid leukaemia, chronic obstructive pulmonary disease) and/or old age were characteristic for all cases. Histological pattern was different in MC-positive and in MC-negative groups: MCCs with MC showed more homogeneous histological pattern, lack of lymphovascular invasion and were associated with better prognosis (mortality rate: 33% versus 80%). MCC associated with oncogenic virus is a newly recognized clinical entity. However, MC could not be detected in all histologically proven MCCs. The well-defined selection of patients/disease groups and better characterization of differences between MC-positive and negative cases is an important step towards the recognition of the etiology and pathogenesis of all MCCs.

Biologic Profiles of Invasive Breast Cancers Detected Only With Digital Breast Tomosynthesis.

PubMed

Kim, Jin You; Kang, Hyun Jung; Shin, Jong Ki; Lee, Nam Kyung; Song, You Seon; Nam, Kyung Jin; Choo, Ki Seok

2017-12-01

The purpose of this study was to analyze the clinicopathologic and immunohistochemical features of invasive breast cancers detected only with digital breast tomosynthesis (DBT), compared with those of cancers detected with both DBT and full-field digital mammography (FFDM). The medical records of 261 women (108 without and 153 with symptoms) with invasive breast cancers who underwent FFDM and DBT between April 2015 and June 2016 were retrospectively reviewed. To assess detectability, all DBT and FFDM images were reviewed independently by three radiologists blinded to clinicopathologic information. The reference standard was established by an unblinded consensus review of all images. Clinicopathologic and immunohistochemical features were analyzed according to the detectability status. Of the 261 cancers, 223 (85.4%) were detected with both DBT and FFDM (both-detected group). Twenty-four cancers (9.2%) not detected with FFDM (DBT-only group) were classified by DBT as a mass (58.3%), architectural distortion (33.3%), or asymmetry (8.3%). The remaining 14 cancers (5.4%) were not detected with either DBT or FFDM (both-occult group). On multivariate analysis, a dense breast parenchyma (p = 0.007), small tumor size (≤ 2 cm; p = 0.027), and luminal A-like subtype (estrogen receptor positive or progesterone receptor positive or both, human epidermal growth factor receptor 2 negative, and Ki-67 expression < 14%; p = 0.008) were significantly associated with the DBT-only group. For 108 screening-detected cancers, a dense breast parenchyma (p = 0.007) and luminal A-like subtype (p = 0.008) also maintained significance. The addition of DBT to FFDM in screening would aid in the detection of less-aggressive subtypes of invasive breast cancers in women with dense breasts.

Expression of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors: Correlation with clinicopathological features.

PubMed

Ciepliński, Klaudiusz; Jóźwik, Maciej; Semczuk-Sikora, Anna; Gogacz, Marek; Lewkowicz, Dorota; Ignatov, Atanas; Semczuk, Andrzej

2018-02-01

The expression of p53 has been studied not only in primary human ovarian carcinomas, but also in borderline ovarian tumors, however, the results were discordant. Expression patterns of proteins involved in cell proliferation and apoptosis have been investigated in various human neoplasms, including female genital tract neoplasms. The aim of this investigation was to assess the staining pattern and immunolocalization of p53 and selected proliferative markers (Ki-67, MCM3, PCNA, and topoisomerase IIα) in borderline ovarian tumors (BOTs). The study group consisted of 42 women who underwent pelvic surgery between 2006-2015. The median patients' age was 46 years. The immunoperoxidase technique was employed using antibodies against p53, Ki-67, MCM3, PCNA, and topoisomerase IIα. For p53, nuclear expression was observed in BOTs, however, cytoplasmatic immunoreactivity was also detected. Altogether, 25 (60%) tumors demonstrated positive p53 immunostaining, including overexpression found in 6 (14%). There were no significant differences in p53 expression between subgroups of clinicopathological variables. Immunoexpression of Ki-67, MCM3, PCNA, and topoisomerase IIα was nuclear. Ki-67 expression was positive in 12 (29%) cases and there was a trend towards a relationship between patients' age and Ki-67 staining (P=0.08). Interestingly, a significantly higher Ki-67 expression was found in tumors of ≥10 cm in diameter compared to smaller tumors (P=0.008). MCM3 expression was detected in 38 (90%) tumors, and PCNA expression in 28 (67%), yet none of clinicopathological factors was related to them. Topoisomerase IIα expression was present in 14 (33%) cases and, interestingly, its significantly higher expression was observed in BOTs of ≥10 cm in diameter compared to smaller tumors (P=0.008). Moreover, Spearman's correlation revealed highly significant positive associations between Ki-67 and topoisomerase IIα (R=0.403, P=0.008) and Ki-67 and MCM3 (R=0.469, P=0.001). We report a high positive immunostaining rate for p53, suggesting a role of TP53 alterations in the development of BOTs in humans. The new finding of higher topoisomerase IIα immunostaining positivity in BOTs of ≥10 cm may be clinically relevant and requires further studies on larger patient groups.

Clinico-pathological features of tuberculosis due to Mycobacterium tuberculosis Uganda genotype in patients with tuberculous lymphadenitis: a cross sectional study.

PubMed

Wamala, Dan; Asiimwe, Benon; Kigozi, Edgar; Mboowa, Gerald; Joloba, Moses; Kallenius, Gunilla

2014-04-02

Tuberculous lymphadenitis is next to pulmonary tuberculosis as the most common cause of tuberculosis. Uganda genotype, one of the sub-lineages of Mycobacterium tuberculosis, is the most prevalent cause of pulmonary tuberculosis in Uganda. We here investigate the clinicopathological characteristics of patients with tuberculous lymphadenitis infected with M. tuberculosis Uganda genotype compared with those infected with M. tuberculosis non-Uganda genotype strains. Between 2010 and 2012, we enrolled 121 patients (mean age 28.5 yrs, male 48%; female 52%) with tuberculous lymphadenitis, and categorized them by their M. tuberculosis genotypes. The clinical features and lymph node cytopathological parameters were compared between patients in the Uganda and non-Uganda categories using a crude and multivariable logistic regression model with adjustment for confounding factors. Of the 121participants, 56 (46%) were infected with strains of Uganda genotype. Patients infected with this genotype had significantly lower frequency of abdominal lymphadenopathy (odds ratio 0.4, p = 0.046) after adjusting for sex, age and HIV. Abdominal lymphadenopathy was also significantly associated with abnormal chest X-ray (p = 0.027). Tuberculous lymphadenitis patients infected with M. tuberculosis Uganda genotype were significantly less prone to have abdominal lymphadenopathy indicating potential reduced ability to disseminate and supporting the concept that differences in M. tuberculosis genotype may have clinical implications.

High-risk borderline ovarian tumors: analysis of clinicopathological features and prognostic impact of different follow-up strategies.

PubMed

Lorusso, Domenica; Ratti, Martina; Ditto, Antonino; Raspagliesi, Francesco

2014-01-01

Borderline ovarian tumors (BOTs) represent 10-20% of all epithelial ovarian malignancies. Most of them are comparable to benign cysts but a high-risk group has been recognized. The aim of the study was to analyze different follow-up strategies in high-risk patients. Patients with BOT treated at our institution from 1992 to 2011 were retrospectively reviewed. Clinicopathological features influencing prognosis were analyzed and two different follow-up strategies compared [6-month laparoscopic look (LPS-look): group A vs. ultrasound/CA-125 evaluation: group B]. 70 patients with high-risk BOTs were identified. After a median progression-free survival (PFS) of 43 months, 27% of patients experienced recurrences. Six months after diagnosis, 26 high-risk patients were submitted to LPS-look: at surgery, 6 out of 10 patients presenting evidence of disease were optimally debulked while in the remaining 4, only biopsies were performed. No difference in PFS was registered between group A and B patients, nevertheless a significant increase in PFS was registered among completely versus incompletely debulked patients with evidence of disease at laparoscopy. Clinical follow-up remains the gold standard for BOTs. These very preliminary data seem to suggest that LPS-look may have an impact on the secondary PFS in a subgroup of high-risk patients. © 2014 S. Karger AG, Basel.

DNMT3B -579 G>T Promoter Polymorphism and the Risk of Gastric Cancer in the West of Iran.

PubMed

Ahmadi, Kulsom; Soleimani, Azam; Irani, Shiva; Kiani, Aliasghar; Ghanadi, Kourosh; Noormohamadi, Zahra; Sakinejad, Foroozan

2018-06-01

Many studies have suggested that modulation of DNMT3B function caused by single nucleotide polymorphisms of the DNMT3B promoter region may underlie the susceptibility to various cancers such as tumors of the digestive system. The aim of this study was to investigate the effect of -579 G>T polymorphism in the promoter of the DNMT3B gene on risk of gastric cancer in a population from West Iran. We conducted a case-control study in 100 gastric cancer patients and 112 cancer-free controls to assess the correlation between DNMT3B -579 G>T (rs1569686) polymorphism and the risk of gastric cancer. Detection of genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. There was no significant difference in the distribution of DNMT3B -579 G>T genotypes between the cases and controls. However, in the stratified analysis by clinicopathological characteristic types, we found that statistically, the risk susceptibility to gastric cancer was significantly associated with tumor grade II and GT/TT genotype of patients, compared to patients having GG genotype, (OR = 5.4737, 95% CI = 1.4746. 20.3184, P = 0.01). Our study suggested that the -579 T allele may increase the relative risk for the progression of clinicopathological characteristic of tumor grade of gastric cancer patients.

Pancreatic Lipase Immunoreactivity in Serum of Dogs with Diabetic Ketoacidosis.

PubMed

Bolton, T A; Cook, A; Steiner, J M; Fosgate, G T

2016-07-01

Diabetic ketoacidosis (DKA) is a relatively common endocrine disorder in dogs and is routinely associated with concurrent pancreatic injury. The aims of this study were to determine the prevalence of pancreatic injury in dogs with DKA based on measurement of pancreatic lipase immunoreactivity in serum (PLI); compare demographic, clinicopathologic, and ultrasonographic findings in dogs with and without evidence of concurrent pancreatic injury; determine the impact of pancreatic injury on duration of hospitalization and short-term outcome. One hundred and nineteen dogs with DKA with or without concurrent pancreatic injury. Retrospective study. Dogs with DKA were divided into three groups on the basis of PLI results: positive for pancreatic injury (PLIpos ), negative for pancreatic injury (PLIneg ), and not tested (PLIna ). Demographics, clinicopathologic test results, findings on abdominal ultrasonography (AUS), duration of hospitalization, and short-term outcome were compared between the three groups. Based on serum PLI activity, 45 dogs (73%) with DKA had evidence of concurrent pancreatic injury. Median total carbon dioxide was significantly lower in the PLIpos dogs compared to the PLIneg dogs. There was fair agreement (κ = 0.26) between serum PLI activity and AUS. Evidence of pancreatic injury was not associated with significantly longer periods of hospitalization (PLIpos median 6 days, range 4-7 days, PLIneg median 4 days, range 3-6 days) and did not influence short-term outcome (PLIpos failure to survive to discharge 11/45, 24%, PLIneg failure to survive to discharge 2/17, 12%). Concurrent pancreatic injury is common in dogs with DKA, but did not affect prognosis in this population of dogs. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Evaluation of promoter methylation status of MLH1 gene in Iranian patients with colorectal tumors and adenoma polyps.

PubMed

Zarandi, Ashkan; Irani, Shiva; Savabkar, Sanaz; Chaleshi, Vahid; Ghavideldarestani, Maryam; Mirfakhraie, Reza; Khodadoostan, Mahsa; Nazemalhosseini-Mojarad, Ehsan; Asadzadeh Aghdaei, Hamid

2017-01-01

The aim of this study was to evaluate the methylation status of the promoter region of MLH1 gene in colorectal cancer (CRC) and its precursor lesions as well as elucidate its association with various clinicopathological characteristics among Iranian population. Epigenetic silencing of mismatch repair genes, such as MLH1 , by methylation of CpG islands of their promoter region has been proved to be an important mechanism in colorectal carcinogenesis. Fifty colorectal cancer and polyp tissue samples including 13 Primary colorectal tumor and 37 Adenoma polyp samples were enrolled in this study. Methylation-specific polymerase chain reaction (MSP) was performed to find the frequency of MLH1 Promoter Methylation. Promoter methylation of MLH1 gene was detected in 5 out of 13 tumor tissues and 4 out of 37 adenoma polyp. The frequency of MLH1 methylation in tumor samples was significantly higher compared to that in polyp tissues (P= 0.026). No significant association was observed between MLH1 promoter methylation and clinicopathological characteristics of the patients. The frequency of  MLH1  promoter methylation in CRC and colon polyp was 18%. Our findings indicated that methylation of MLH1 promoter region alone cannot be considered as a biomarker for early detection of CRC.

HOXB9 Expression Correlates with Histological Grade and Prognosis in LSCC

PubMed Central

2017-01-01

The purpose of this study was to investigate the HOX gene expression profile in laryngeal squamous cell carcinoma (LSCC) and assess whether some genes are associated with the clinicopathological features and prognosis in LSCC patients. The HOX gene levels were tested by microarray and validated by qRT-PCR in paired cancerous and adjacent noncancerous LSCC tissue samples. The microarray testing data of 39 HOX genes revealed 15 HOX genes that were at least 2-fold upregulated and 2 that were downregulated. After qRT-PCR evaluation, the three most upregulated genes (HOXB9, HOXB13, and HOXD13) were selected for tissue microarray (TMA) analysis. The correlations between the HOXB9, HOXB13, and HOXD13 expression levels and both clinicopathological features and prognosis were analyzed. Three HOX gene expression levels were markedly increased in LSCC tissues compared with adjacent noncancerous tissues (P < 0.001). HOXB9 was found to correlate with histological grade (P < 0.01) and prognosis (P < 0.01) in LSCC. In conclusion, this study revealed that HOXB9, HOXB13, and HOXD13 were upregulated and may play important roles in LSCC. Moreover, HOXB9 may serve as a novel marker of poor prognosis and a potential therapeutic target in LSCC patients. PMID:28808656

Comparison of Clinical Characteristic and Prognosis between Ovarian Clear Cell Carcinoma and Serous Carcinoma: A 10-Year Cohort Study of Chinese Patients.

PubMed

Ye, Shuang; Yang, Jiaxin; You, Yan; Cao, Dongyan; Huang, Huifang; Wu, Ming; Chen, Jie; Lang, Jinghe; Shen, Keng

2015-01-01

To compare the clinicopathologic features and prognosis of Chinese patients with ovarian clear cell carcinoma (CCC) and serous carcinoma (SC). A retrospective cohort study was designed to investigate the clinicopathologic characteristic and prognosis of patients with CCC and SC who were diagnosed and treated in in a tertiary referral center (Peking Union Medical College Hospital) between 1999 and 2009. The Kaplan-Meier method and Cox regression were employed in the survival analysis. A total of 504 cases were included in the study, comprising 197 cases of CCC and 307 cases of SC. The mean age of the patients with SC was greater than of CCC patients (3.6±0.94, P<0.001). Patients with CCC were more likely to be early-stage and optimally debulked (P<0.001). Regarding cancer-antigen 125, 22% of the patients with CCC had normal values, and the level was significantly lower than in patients with SC (P<0.001). More CCC patients had platinum-resistant tumors compared with platinum-sensitive disease (45.7% in CCC vs. 61.0% in SC [P=0.008]). The 5-year survival rate was 51.2% in the CCC group vs. 49.8% in the SC group (P=0.428). Patients with advanced CCC had a statistically significant poorer overall survival (OS) compared with their SC counterparts (38.0 vs. 52.0 months; hazard ratio 1.584, 95% confidence interval [CI] 1.167-2.150, P=0.003). However, the advantage of improved progression-free survival (PFS) existed across all stages. Women with ovarian CCC presented at a younger age and early stage. Patients with ovarian CCC also had improved PFS, but they had similar OS compared to patients with SC. However, patients with advanced CCC had decreased survival.

Clinico-pathological features of kidney disease in diabetic cases.

PubMed

Furuichi, Kengo; Shimizu, Miho; Okada, Hirokazu; Narita, Ichiei; Wada, Takashi

2018-03-21

Diabetic kidney disease is the major cause of end-stage kidney disease in developed countries. However, the onset of kidney disorder and the progression pattern of kidney dysfunction and proteinuria greatly vary cases by cases. Therefore, risk classification with clinical data and pathological findings is important. Recent clinico-pathological study with kidney biopsy samples from diabetic patients revealed that pathological changes of diabetic nephropathy are characteristic and have special impacts on prognosis in each clinical stage. Moreover, comparison of the clinico-pathological findings of diabetic nephropathy with hypertensive nephrosclerosis revealed that there are few differences in their pathological findings in cases with low albuminuria and preserved estimated glomerular filtration rate (eGFR). Because it is so difficult to clearly distinguish pure kidney lesions caused by diabetes and kidney lesions due to effects other than diabetes, it is vital that these overlapped pathological findings be confirmed on kidney biopsy in cases of early stage diabetes. Further research is warranted regarding the pathogenesis of diabetic nephropathy and indication of kidney biopsy in diabetic cases.

Preparation of a novel antiserum to aromatase with high affinity and specificity: Its clinicopathological significance on breast cancer tissue.

PubMed

Kanomata, Naoki; Matsuura, Shiro; Nomura, Tsunehisa; Kurebayashi, Junichi; Mori, Taisuke; Kitawaki, Jo; Moriya, Takuya

2017-01-01

Aromatase inhibitors have been widely used for the endocrine treatment of estrogen-dependent breast cancer in postmenopausal patients. However, clinicopathological studies of aromatase have been limited due to unsatisfactory specificity and/or restricted availability of anti-aromatase antibodies. Here, we have generated a polyclonal antiserum with high affinity and specificity for human aromatase using a monoclonal antibody tagged immunoaffinity chromatography on an industrial production scale. Our preliminary immunohistochemical analysis of 221 invasive breast cancer cases indicated that 87.3% (193/221) had at least 5% aromatase positive cells. The histoscore for aromatase was inversely correlated with pT (p = 0.019), pN (p = 0.001), stage (p < 0.001), histologic grade (p = 0.003), lymphatic infiltration (p < 0.001), venous infiltration (p < 0.001), and Ki-67 index (p < 0.001). However, cancer aromatase expression was independent of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 statuses. This antiserum will be applicable to clinicopathological examination of aromatase in addition to ER and PgR for an appropriate use of aromatase inhibitor on the treatment of breast cancer. Further studies on the relationship between Aromatase inhibitors have been widely used for the endocrine treatment of estrogen-dependent breast cancer in postmenopausal patients. However, clinicopathological studies of aromatase have been limited due to unsatisfactory specificity and/or restricted availability of anti-aromatase antibodies. Here, we have generated a polyclonal antiserum with high affinity and specificity for human aromatase using a monoclonal antibody tagged immunoaffinity chromatography on an industrial production scale. Our preliminary immunohistochemical analysis of 221 invasive breast cancer cases indicated that 87.3% (193/221) had at least 5% aromatase positive cells. The histoscore for aromatase was inversely correlated with pT (p = 0.019), pN (p = 0.001), stage (p < 0.001), histologic grade (p = 0.003), lymphatic infiltration (p < 0.001), venous infiltration (p < 0.001), and Ki-67 index (p < 0.001). However, cancer aromatase expression was independent of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 statuses. This antiserum will be applicable to clinicopathological examination of aromatase in addition to ER and PgR for an appropriate use of aromatase inhibitor on the treatment of breast cancer. Further studies on the relationship between aromatase expression and aromatase inhibitors are warranted.

Refined estimates of local recurrence risks by DCIS score adjusting for clinicopathological features: a combined analysis of ECOG-ACRIN E5194 and Ontario DCIS cohort studies.

PubMed

Rakovitch, E; Gray, R; Baehner, F L; Sutradhar, R; Crager, M; Gu, S; Nofech-Mozes, S; Badve, S S; Hanna, W; Hughes, L L; Wood, W C; Davidson, N E; Paszat, L; Shak, S; Sparano, J A; Solin, L J

2018-06-01

Better tools are needed to estimate local recurrence (LR) risk after breast-conserving surgery (BCS) for DCIS. The DCIS score (DS) was validated as a predictor of LR in E5194 and Ontario DCIS cohort (ODC) after BCS. We combined data from E5194 and ODC adjusting for clinicopathological factors to provide refined estimates of the 10-year risk of LR after treatment by BCS alone. Data from E5194 and ODC were combined. Patients with positive margins or multifocality were excluded. Identical Cox regression models were fit for each study. Patient-specific meta-analysis was used to calculate precision-weighted estimates of 10-year LR risk by DS, age, tumor size and year of diagnosis. The combined cohort includes 773 patients. The DS and age at diagnosis, tumor size and year of diagnosis provided independent prognostic information on the 10-year LR risk (p ≤ 0.009). Hazard ratios from E5194 and ODC cohorts were similar for the DS (2.48, 1.95 per 50 units), tumor size ≤ 1 versus  > 1-2.5 cm (1.45, 1.47), age ≥ 50 versus < 50 year (0.61, 0.84) and year ≥ 2000 (0.67, 0.49). Utilization of DS combined with tumor size and age at diagnosis predicted more women with very low (≤ 8%) or higher (> 15%) 10-year LR risk after BCS alone compared to utilization of DS alone or clinicopathological factors alone. The combined analysis provides refined estimates of 10-year LR risk after BCS for DCIS. Adding information on tumor size and age at diagnosis to the DS adjusting for year of diagnosis provides improved LR risk estimates to guide treatment decision making.

Molecular spectrum of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC somatic gene mutations in Arab patients with colorectal cancer: determination of frequency and distribution pattern

PubMed Central

Al-Shamsi, Humaid O.; Jones, Jeremy; Fahmawi, Yazan; Dahbour, Ibrahim; Tabash, Aziz; Abdel-Wahab, Reham; Abousamra, Ahmed O. S.; Shaw, Kenna R.; Xiao, Lianchun; Hassan, Manal M.; Kipp, Benjamin R.; Kopetz, Scott; Soliman, Amr S.; McWilliams, Robert R.; Wolff, Robert A.

2016-01-01

Background The frequency rates of mutations such as KRAS, NRAS, BRAF, and PIK3CA in colorectal cancer (CRC) differ among populations. The aim of this study was to assess mutation frequencies in the Arab population and determine their correlations with certain clinicopathological features. Methods Arab patients from the Arab Gulf region and a population of age- and sex-matched Western patients with CRC whose tumors were evaluated with next-generation sequencing (NGS) were identified and retrospectively reviewed. The mutation rates of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC were recorded, along with clinicopathological features. Other somatic mutation and their rates were also identified. Fisher’s exact test was used to determine the association between mutation status and clinical features. Results A total of 198 cases were identified; 99 Arab patients and 99 Western patients. Fifty-two point seven percent of Arab patients had stage IV disease at initial presentation, 74.2% had left-sided tumors. Eighty-nine point two percent had tubular adenocarcinoma and 10.8% had mucinous adenocarcinoma. The prevalence rates of KRAS, NRAS, BRAF, PIK3CA, TP53, APC, SMAD, FBXW7 mutations in Arab population were 44.4%, 4%, 4%, 13.1%, 52.5%, 27.3%, 2% and 3% respectively. Compared to 48.4%, 4%, 4%, 12.1%, 47.5%, 24.2%, 11.1% and 0% respectively in matched Western population. Associations between these mutations and patient clinicopathological features were not statistically significant. Conclusions This is the first study to report comprehensive hotspot mutations using NGS in Arab patients with CRC. The frequency of KRAS, NRAS, BRAF, TP53, APC and PIK3CA mutations were similar to reported frequencies in Western population except SMAD4 that had a lower frequency and higher frequency of FBXW7 mutation. PMID:28078112

Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma.

PubMed

Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi

2017-06-27

Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients' overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment.

Prognostic value of cancer stem cell marker CD133 expression in pancreatic ductal adenocarcinoma (PDAC): a systematic review and meta-analysis.

PubMed

Li, Xiaoping; Zhao, Haojie; Gu, Jianchun; Zheng, Leizhen

2015-01-01

CD133 is one of the most commonly used markers of pancreatic cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. Although the expression of CD133 has been reported to correlate with poor prognosis of PDAC in most literatures, some controversies still exist. In this study, we aimed to investigate the correlation between CD133 expression and prognosis and clinicopathological features in PDAC. A search in the Medline, EMBASE and Chinese CNKI (China National Knowledge Infrastructure) database (up to 1 March 2015) was performed using the following keywords pancreatic cancer, CD133, AC133, prominin-1 etc. Data from eligible studies were extracted and included into meta-analysis using a random effects model. Outcomes included overall survival and various clinicopathological features. We performed a final analysis of 723 patients from 11 evaluable studies for prognostic value and 687 patients from 12 evaluable studies for clinicopathological features. Our study shows that the pooled hazard ratio (HR) of overexpression CD133 for overall survival in PDAC was 0.58 (95% confidence interval (CI): 0.49-0.67) by univariate analysis and 0.73 (95% CI: 0.52-1.03) by multivariate analysis. With respect to clinicopathological features, CD133 overexpression by immunohistochemistry (IHC) method was closely correlated with clinical TNM stage (TNM stage III+IV, OR=0.32, 95% CI: 0.19-0.54), tumor differentiation (poor differentiation, OR=0.56, 95% CI: 0.37-0.83), and lymph node metastasis (N1, 3.15, 95% CI: 1.56-6.36) in patients with PDAC. Our meta-analysis results suggest that CD133 is an efficient prognostic factor in PDAC. Overexpression of CD133 was significantly associated with clinical TNM stage, tumor differentiation and lymph node metastasis.

Clinicopathologic Features and Results of Transcatheter Arterial Chemoembolization for Osteosarcoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chu Jianping; Chen Wei; Li Jiaping

2007-04-15

Purpose. To evaluate the effect of transcatheter arterial chemoembolization (TACE) for osteosarcoma and to describe the clinicopathologic features produced by TACE as well as the effect of different embolic materials. Methods. From January 1998 to December 2003, preoperative TACE was carried out in 32 patients. The preoperative and postoperative clinical response, levels of alkaline phosphatase (AKP), leukocyte count, and clinicopathologic features were recorded. We also compared the effect of different embolic materials: adriblastine gelatin microspheres, anhydrous alcohol, common bletilla tuber, and gelatin sponge particles. Results. The levels of AKP were significantly decreased after treatment (p < 0.05), but there wasmore » no significant difference in the leukocyte count. Large areas of necrosis were found histologically within 85.5% tumors after TACE. Embolic agents such as adriblastine microspheres, anhydrous alcohol, and common bletilla tuber have better clinical effects than gelatin sponge particles, but there was no significant difference among the first three embolic materials. After treatment, no serious complications were noted. During successful follow-up for 86 months, the survival rate after TACE at 1, 2, and 5 years was 95.5%, 72%, and 42% respectively. Conclusion. TACE accelerated tumor necrosis and shrank the tumor volume, thus making adequate tumor resection possible. The optimal time to operate is 10-14 days after TACE. TACE in combination with limb salvage surgery and postoperative periodical chemotherapy may be beneficial for increasing local control rates.« less

[Clinico-pathology of lobular breast cancer].

PubMed

Langmár, Z; Orosz, Z

1999-05-16

997 operations were performed because of malignant breast lesions at the National Institute of Oncology during a two-years period (1990-1991). Histologically 94 tumours proved to be invasive lobular cancer. Comparable data were available for 89 patients; a questionnaire was used for data collection. Analysing these cases, the authors discuss the clinicopathology of lobular cancer and current practice in its treatment. The mean age of the patients was 57.1 years, which in accordance with the literature. No synchronous contralateral tumour was observed in the studied patient group. 4.9% of the cases proved to be multifocal, what is considerably less than that reported in the literature. It is a frequent matter of debate in many papers whether mastectomy should be indicated if the multicentricity of the tumour is only suspected. The features of the studied group may also emphasise this question, and further investigation is needed for moderating the surgical radicality. The rate of large tumours and the mean tumour diameter was lower than suggested by the literature. The rate of positive axillary lymph nodes was higher than in reports of other centres. The authors underline the necessity of axillary block-dissection even in case of operations with decreased radicality. Beside lymph node metastases, invasive lobular cancer produces haematogenous metastases with a higher probabilty than other breast cancers. This observation is supported by our study, too.

Role of lymphatic vessel density in colorectal cancer: prognostic significance and clinicopathologic correlations.

PubMed

Pappas, A; Lagoudianakis, E; Seretis, C; Koronakis, N; Keramidaris, D; Grapatsas, K; Filis, K; Manouras, A; Salemis, N

2015-06-01

Over the past decades the identification of several molecules that are expressed specifically in the lymphatic endothelial cells has resulted in marked advances in the field of lymphangiogenesis. We aimed to measure LVD in colorectal cancer patients and to compare it with microvascular density (MVD) - a marker of angiogenesis - and patients' clinicopathological parameters and survival, as the measurement of lymphatic vessel density (LVD) has been documented in various tumor types, including colorectal cancer. Fifty one patients who had undergone surgical resection for stage I-III colorectal cancer entered this study. LVD and MVD were determined immunohistochemically with the use of D2-40 and CD34 antibody respectively. The evaluation of LVD was performed by both visual and computer-aided image analysis. The majority of lymphatic vessels were located in the peritumoral areas rather than within the tumor. The results obtained from the image analyzer correlated significantly with the data obtained using visual counting with light microscopy. Both visual and image analysis LVD failed to correlate with patients' age and gender and tumor location, stage, grade, MVD count and survival. The biologic role of the lymphatic vasculature in tumor progression remains controversial. The present study failed to associate LVD with outcome markers and prognosis and further studies would be required to verify our results. © Acta Gastro-Enterologica Belgica.

Prediction of overall survival in stage II and III colon cancer beyond TNM system: a retrospective, pooled biomarker study.

PubMed

Dienstmann, R; Mason, M J; Sinicrope, F A; Phipps, A I; Tejpar, S; Nesbakken, A; Danielsen, S A; Sveen, A; Buchanan, D D; Clendenning, M; Rosty, C; Bot, B; Alberts, S R; Milburn Jessup, J; Lothe, R A; Delorenzi, M; Newcomb, P A; Sargent, D; Guinney, J

2017-05-01

TNM staging alone does not accurately predict outcome in colon cancer (CC) patients who may be eligible for adjuvant chemotherapy. It is unknown to what extent the molecular markers microsatellite instability (MSI) and mutations in BRAF or KRAS improve prognostic estimation in multivariable models that include detailed clinicopathological annotation. After imputation of missing at random data, a subset of patients accrued in phase 3 trials with adjuvant chemotherapy (n = 3016)-N0147 (NCT00079274) and PETACC3 (NCT00026273)-was aggregated to construct multivariable Cox models for 5-year overall survival that were subsequently validated internally in the remaining clinical trial samples (n = 1499), and also externally in different population cohorts of chemotherapy-treated (n = 949) or -untreated (n = 1080) CC patients, and an additional series without treatment annotation (n = 782). TNM staging, MSI and BRAFV600E mutation status remained independent prognostic factors in multivariable models across clinical trials cohorts and observational studies. Concordance indices increased from 0.61-0.68 in the TNM alone model to 0.63-0.71 in models with added molecular markers, 0.65-0.73 with clinicopathological features and 0.66-0.74 with all covariates. In validation cohorts with complete annotation, the integrated time-dependent AUC rose from 0.64 for the TNM alone model to 0.67 for models that included clinicopathological features, with or without molecular markers. In patient cohorts that received adjuvant chemotherapy, the relative proportion of variance explained (R2) by TNM, clinicopathological features and molecular markers was on an average 65%, 25% and 10%, respectively. Incorporation of MSI, BRAFV600E and KRAS mutation status to overall survival models with TNM staging improves the ability to precisely prognosticate in stage II and III CC patients, but only modestly increases prediction accuracy in multivariable models that include clinicopathological features, particularly in chemotherapy-treated patients. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Apoptotic and proliferative status in HPV (+) and HPV (-) inverted papilloma patients. Correlation with local recurrence and clinicopathological variables.

PubMed

Giotakis, Evagelos; Gomatos, Ilias P; Alevizos, Leonidas; Manolopoulos, Leonidas; Kataki, Agapi; Kandiloros, Dimitris; Gorgoulis, Vassilis G; Tsimaratou, Katerina; Konstantoulakis, Manousos M; Yiotakis, Ioannis

2012-06-15

Inverted papilloma (IP) is a rare sinonasal benign lesion characterized by aggressive biological behavior. Our aim was to evaluate the expression of various proliferation and apoptotic markers and the presence of HPV genotypes in paraffin sections gathered from surgically treated IP patients. Immunohistochemistry for PCNA, bax, cytochrome c and caspase-8 and flow cytometry for the detection of apoptosis, necrosis and ki67 expression were performed. The identification of various HPV subtypes was achieved by nested PCR amplification. Nasal polyps (NP) and specimens from normal nasal epithelium (NE) were used as controls. PCNA was more frequently expressed in IP compared to NE (p=0.04) and caspase-8 and bax staining were less frequently observed in IP compared to NP (p=0.004 and p=0.01 respectively) and NE (p=0.003 and p=0.01, respectively). IP and NP presented significantly higher Ki67 flow cytometry values compared to NE (p<0.001 and p=0.02 respectively). Cytochrome c was more frequently expressed in IP specimens with more prominent inflammation (p=0.02). A low HPV DNA detection rate was observed. Neither HPV status nor any of the apoptotic or proliferative markers studied was associated with the patients' clinicopathological characteristics. Increased Ki67 appeared to correlate with disease recurrence (p=0.01). Increased PCNA and Ki67 and decreased bax and caspase-8 expression indicate that cell proliferation is increased while apoptosis is inhibited in IP, explaining its biological behavior. Copyright © 2012 Elsevier GmbH. All rights reserved.

SMAD7 loci contribute to risk of hepatocellular carcinoma and clinicopathologic development among Chinese Han population.

PubMed

Ji, Jiansong; Xu, Min; Zhao, Zhongwei; Tu, Jianfei; Gao, Jun; Lu, Chenying; Song, Jingjing; Chen, Weiqian; Chen, Minjiang; Fan, Xiaoxi; Cheng, Xingyao; Lan, Xilin; Li, Jie

2016-04-19

Genome-wide association studies (GWAS) have identified three loci at 18q21 (rs4939827, rs7240004, and rs7229639), which maps to SMAD7 loci, were associated with risk of diseases of the digestive system. However, their associations with hepatocellular carcinoma (HCC) risk remain unknown. A case-control study was conducted to assess genetic associations with HCC risk and clinicopathologic development among Chinese Han population. Three SNPs were genotyped among 1,000 HCC cases and 1,000 controls using Sequenom Mass-ARRAY technology. We observed statistically significant associations for the three SMAD7 loci and HCC risk. Each copy of minor allele was associated with a 1.24-1.36 fold increased risk of HCC. We also found that significant differences were observed between rs4939827 and clinical TNM stage and vascular invasion, as well as rs7240004 and vascular invasion. We also established a genetic risk score (GRS) by summing the risk alleles. The GRS was significantly associated with increased risk of HCC and vascular invasion. Our data revealed the SMAD7 loci is associated with HCC susceptibility and its clinicopathologic development.

MicroRNA-367 is a potential diagnostic biomarker for patients with esophageal squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Jiangtao; Song, Kaifang; Feng, Xiaoshan, E-mail: xiaoshan.feng@aol.com

Purpose: In this study, we investigated whether microRNA-367 (miR-367) may serve as a circulating biomarker and tumor oncogene in esophageal squamous carcinoma (ESCC). Methods: Circulating serum miR-367 was compared by quantitative RT-PCR (qRT-PCR) between 35 ESCC patients and 35 normal control patients, as well paired ESCC tumor tissues and adjacent non-tumor esophageal epithelial tissues in 46 patients. The correlation between serum miR-367 and clinicopathological properties of ESCC patients was assessed. The overall survival (OS) was assessed by Kaplan–Meier method and compared by log-rank test between patients with high serum miR-367 and low serum miR-367. The possibility of miR-367 being independentmore » prognostic factor for ESCC was also assessed. Furthermore, lentivirus-mediated miR-367 downregulation was conducted in ESCC cell lines Kyse30 and TE-1 cells to assess the possible oncogenic effect of miR-367 on ESCC proliferation and cell cycle transition in vitro. Results: MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients, whereas downregulated in ESCC patients after the treatments of esophagectomy and chemotherapy. Serum miR-367 was found to be closely correlated with the clinicopathological properties of differentiation grades, clinical stage and tumor metastasis in ESCC patients. Serum miR-367 was also confirmed to be associated with OS, as well as serving independent prognostic factor in ESCC patients. Moreover, lentivirus-induced miR-367 downregulation inhibited cancer growth and cell cycle transition in Kyse30 and TE-1 cells. Conclusion: MiR-367 is a potential biomarker for ESCC and may act as an oncogene in regulating ESCC development. - Highlights: • MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients. • MiR-367 was downregulated in ESCC patients after esophagectomy or chemotherapy. • Serum miR-367 was correlated with the clinicopathological properties of ESCC patients. • Serum miR-367 was associated with OS in ESCC patients. • lentivirus-induced miR-367 downregulation inhibited ESCC growth and cell cycle transition.« less

Synchronous and metachronous neoplasms in gastric cancer patients: A 23-year study

PubMed Central

Ławniczak, Małgorzata; Gawin, Alicja; Jaroszewicz-Heigelmann, Halina; Rogoza-Mateja, Wiesława; Raszeja-Wyszomirska, Joanna; Białek, Andrzej; Karpińska-Kaczmarczyk, Katarzyna; Starzyńska, Teresa

2014-01-01

AIM: To determine the prevalence and characteristics of additional primary malignancies in gastric cancer (GC) patients. METHODS: GC patients (862 total; 570 men, 292 women; mean age 59.8 ± 12.8 years) diagnosed at the Department of Gastroenterology at Pomeranian Medical University over a period of 23 years were included in this retrospective analysis of a prospectively maintained database. Mean follow-up time was 31.3 ± 38.6 mo (range 1-241 mo). The following clinicopathological features of patients with synchronous tumors were compared to those with metachronous tumors: age, sex, symptom duration, family history of cancer, tumor site, stage (early vs advanced), histology, and blood group. GC patients with and without a second tumor were compared in terms of the same clinicopathological features. RESULTS: Of 862 GC patients, 58 (6.7%) developed a total of 62 multiple primary tumors, of which 39 (63%) were metachronous and 23 (37%) synchronous. Four (6.9%) of the 58 multiple GC patients developed two or more neoplasms. The predominant tumor type of the secondary neoplasms was colorectal (n = 17), followed by lung (n = 9), breast (n = 8), and prostate (n = 7). Age was the only clinicopathological feature that differed between GC patients with synchronous vs metachronous malignancies; GC patients with synchronous neoplasms were older than those with metachronous neoplasms (68.0 ± 10.3 years vs 59.9 ± 11.1 years, respectively, P = 0.008). Comparisons between patients with and without a second primary cancer revealed that the only statistically significant differences were in age and blood group. The mean age of the patients with multiple GC was higher than that of those without a second primary tumor (63.4 ± 11.4 years vs 59.5 ± 13.0 years, respectively, P = 0.026). GC patients with a second primary tumor were more commonly blood group O than those without (56.2% vs 31.6%, respectively, P = 0.002). CONCLUSION: GC patients may develop other primary cancers; appropriate preoperative and postoperative diagnostic modalities are thus required, particularly if patients are older and blood group O. PMID:24966619

Clinical manifestations of colorectal cancer patients from a large multicenter study in Colombia.

PubMed

Bohorquez, Mabel; Sahasrabudhe, Ruta; Criollo, Angel; Sanabria-Salas, María Carolina; Vélez, Alejandro; Castro, Jorge Mario; Marquez, Juan Ricardo; Mateus, Gilbert; Bolaños, Fernando; Panqueva, Cesar; Restrepo, Jose Ignacio; Puerta, Juan Dario; Murillo, Raul; Bravo, María Mercedes; Hernández, Gustavo; Rios, Angela; Prieto, Rodrigo; Tomlinson, Ian; Echeverry, Magdalena; Carvajal-Carmona, Luis G

2016-10-01

Colorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America.The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations.The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P = 0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3-T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P = 0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P = 0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P = 0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P = 0.005) and report a family history of cancer (17.4% vs 10.2%; P = 0.001).To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations.

Clinical manifestations of colorectal cancer patients from a large multicenter study in Colombia

PubMed Central

Bohorquez, Mabel; Sahasrabudhe, Ruta; Criollo, Angel; Sanabria-Salas, María Carolina; Vélez, Alejandro; Castro, Jorge Mario; Marquez, Juan Ricardo; Mateus, Gilbert; Bolaños, Fernando; Panqueva, Cesar; Restrepo, Jose Ignacio; Puerta, Juan Dario; Murillo, Raul; Bravo, María Mercedes; Hernández, Gustavo; Rios, Angela; Prieto, Rodrigo; Tomlinson, Ian; Echeverry, Magdalena; Carvajal-Carmona, Luis G.

2016-01-01

Abstract Colorectal cancer (CRC) is a major public health problem, and its incidence is rising in developing countries. However, studies characterizing CRC clinicopathological features in cases from developing countries are still lacking. The goal of this study was to evaluate clinicopathological and demographic features in one of the largest CRC studies in Latin America. The study involved over 1525 CRC cases recruited in a multicenter study in Colombia between 2005 and 2014 as part of ongoing genetic and epidemiological studies. We gathered clinicopathological data such as age at diagnosis, sex, body mass index, tobacco and alcohol consumption, family history of cancer, and tumor features including location, histological type, and stage. Statistical analyses were performed to test the association between age of onset, sex, and clinical manifestations. The average age at CRC diagnosis was 57.4 years, with 26.5% of cases having early-onset CRC (diagnosed by age 50 years). Most cases were women (53.2%; P = 0.009), 49.2% were overweight or obese, 49.1% were regular alcohol drinkers, 52% were smokers/former smokers, and 12.2% reported relatives with cancer. Most tumors in the study were located in the rectum (42.7%), were adenocarcinomas (91.5%), and had advanced stage (T3–T4, 79.8%). Comparisons by sex found that male cases were more likely to be obese (36.5% vs 31.1%; P = 0.001), less likely to have a family history of cancer (9.7% vs 15.3%; P = 0.016), and more likely to have advanced-stage tumors (83.9% vs 76.1%; P = 0.036). Comparisons by age of onset found that early-onset cases were more likely to be women (59.3% vs 51.0%; P = 0.005) and report a family history of cancer (17.4% vs 10.2%; P = 0.001). To our knowledge, our study is the largest report of clinicopathological characterization of Hispanic CRC cases, and we suggest that further studies are needed to understand CRC etiology in diverse Hispanic populations. PMID:27749544

CD44v6 expression in patients with stage II or stage III sporadic colorectal cancer is superior to CD44 expression for predicting progression

PubMed Central

Zhao, LH; Lin, QL; Wei, J; Huai, YL; Wang, KJ; Yan, HY

2015-01-01

Background: Currently, it is difficult to predict the prognosis of patients exhibiting stage II or stage III colorectal cancer (CRC) and to identify those patients most likely to benefit from aggressive treatment. The current study was performed to examine the clinicopathological significance of CD44 and CD44v6 protein expression in these patients. Study design: We retrospectively investigated 187 consecutive patients who underwent surgery with curative intent for stage II to III CRC from 2007 to 2013 in the Beijing Civil Aviation Hospital. CD44 and CD44v6 protein expression levels were determined using immunohistochemistry and compared to the clinicopathological data. Results: Using immunohistochemical detection, CD44 expression was observed in 108 (57.75%) of the CRC patients; and its detection was significantly associated with greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological tumor-lymph node-metastasis (TNM) stage. CD44v6 expression was observed in 135 (72.19%) of the CRC patients; and its expression was significantly associated with a poorly differentiated histology, greater invasion depth, lymph node metastasis, angiolymphatic invasion, and a more advanced pathological TNM stage. Expression of CD44v6 was higher than that of CD44 in stage II and stage III sporadic CRC. Conclusion: CD44v6 is a more useful marker for predicting a poor prognosis in stage II and stage III sporadic CRC as compared to CD44. PMID:25755763

A clinicopathological study of surgically resected lung cancer in patients with usual interstitial pneumonia.

PubMed

Watanabe, Yasutaka; Kawabata, Yoshinori; Koyama, Nobuyuki; Ikeya, Tomohiko; Hoshi, Eishin; Takayanagi, Noboru; Koyama, Shinichiro

2017-08-01

The clinicopathological characteristics of lung cancer with concomitant usual interstitial pneumonia (UIP) are insufficiently understood. This study aimed to elucidate a characteristic pathological feature of lung cancer that develops in patients with UIP, with a focus on the location of its onset. We reviewed surgically obtained specimens, including 547 tumors from 526 patients who underwent lobectomy for lung cancer. Surveyed patients were classified into three groups: patients with UIP (UIP group), patients with lung pathology other than UIP (non-UIP group), and patients without any associated lung pathology (normal group). The histology as well as the lobe and location of the onset of lung cancer were compared among these groups. The peripheral location was subdivided into subpleural, inner and tumor involved centrally secondary to extension. The UIP group comprised 82 patients (male, 71 [87%]; mean age, 71 years; smoking rate, 94%), the non-UIP group comprised 334 patients (male, 267 [80%]; mean age, 69 years; smoking rate, 81%), and the normal group comprised 110 patients (male, 33 [30%]; mean age, 63; smoking rate, 29%). No statistical differences were noted in sex, mean age, or smoking index between the UIP and non-UIP groups. Compared with the non-UIP group, the frequency of squamous cell carcinoma (63% vs. 32%), lower lobe origin (76% vs. 32%), and subpleural location (24% vs. 5%) were significantly higher in the UIP group. Lung cancers in patients with UIP show a predilection for the subpleural region, where UIP is also thought to originate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinicopathological analysis of salivary gland tumors over a 15-year period.

PubMed

Vasconcelos, Artur Cunha; Nör, Felipe; Meurer, Luise; Salvadori, Gabriela; Souza, Lélia Batista de; Vargas, Pablo Agustin; Martins, Manoela Domingues

2016-01-01

Salivary gland tumors (SGT) are rare neoplasms that generate interest due to their histopathological diversity and clinical behavior. The aims of the present study were to investigate clinicopathological aspects of SGTs diagnosed at a tertiary health center and compare the findings with epidemiological data from different geographic locations. Cases of tumor in the head and neck region at a single health center in the period between 1995 and 2010 were reviewed. Patient gender, age and ethnic group as well as anatomic location, histological type and clinical behavior of the tumor were recorded. Availability of complete information about these aspects was considered the inclusion criteria. Descriptive statistical analysis of the data was performed using the frequencies of categorical variables. Among the 2168 cases of tumors in the head and neck region, 243 (11.20%) cases were diagnosed in the salivary glands, 109 of which met the inclusion criteria: 85 (78%) benign tumors and 24 (22%) malignant tumors. Mean patient age was 46.47 years. The female gender accounted for 56 cases (51.4%) and the male gender accounted for 53 (48.3%). The major salivary glands were affected more (75.2%) than the minor glands. The most frequent benign and malignant SGTs were pleomorphic adenoma (81.2%) and adenoid cystic carcinoma (58.3%), respectively. In conclusion, pleomorphic adenoma and adenoid cystic carcinoma are the most frequent benign and malignant lesions, respectively. Comparing the present data with previous studies on SGTs, one may infer that some demographic characteristics and the predominance of malignant tumors vary in different geographic regions.

Clinicopathological study of 81 cases of localized and systemic scleroderma.

PubMed

Succaria, F; Kurban, M; Kibbi, A-G; Abbas, O

2013-02-01

Scleroderma is a connective tissue disease that includes localized and systemic forms. Our recent encounter with a morphea case exhibiting prominent perineural inflammation microscopically prompted us to assess the features of all patients diagnosed with morphea/scleroderma at our institution. To describe the clinicopathological features of all patients diagnosed with morphea/scleroderma at American University of Beirut Medical Center (AUB-MC) between 1999 and 2010, and compare our findings with those published in the literature. A total of 81 cases (63 women and 18 men) were identified, of which 73 were localized (morphea) and eight were systemic scleroderma. Clinically, plaque type morphea was the most common variant both in adults and children, and seven (9%) cases of morphea were associated with lichen sclerosis et atrophicus (LSA). Histopathologically, perineural inflammation was observed in 49% of cases, and may serve, in addition to other features including lichen sclerosis-like changes (observed in exclusively nine cases of morphea), more diffuse dermal and less subcutaneous sclerosis, and intense inflammation, as clues favouring diagnosis of morphea over systemic sclerosis. The features of morphea/scleroderma patients in this study are generally comparable to those published in the literature, with few differences. Clinically, plaque type morphea was the most common variant both in adults and children and LSA was a frequent association. Histopathologically, perineural inflammation was commonly observed and may serve in addition to lichen sclerosis-like changes and intense inflammation as clues favouring diagnosis of morphea over systemic sclerosis. © 2012 The Authors. Journal of the European Academy of Dermatology and Venereology © 2012 European Academy of Dermatology and Venereology.

Early diagnostic role of PSA combined miR-155 detection in prostate cancer.

PubMed

Guo, T; Wang, X-X; Fu, H; Tang, Y-C; Meng, B-Q; Chen, C-H

2018-03-01

As a kind of malignant tumor in the male genitourinary system, prostate cancer exhibits significantly increased occurrence. Prostate-specific antigen (PSA) expression can be seen in the prostate cancer, prostatitis, and other diseases, therefore, lack of diagnostic specificity. The miR-155 expression is abnormally increased in the tumors. Therefore, this study aims to explore the clinical significance of PSA combined miR-155 detection in the early diagnosis of prostate cancer. A total of 86 patients diagnosed with prostate cancer were enrolled in this study. PSA and miR-155 gene expression in tumor tissue were detected by using Real-time PCR. The serum levels of PSA were measured by using enzyme-linked immunosorbent assay (ELISA). The correlation of PSA and miR-155 expression with age, body mass index (BMI), tumor volume, tumor-node-metastasis (TNM) stage, lymph node metastasis (LNM), and other clinicopathological features were analyzed, respectively. Serum PSA expression and PSA gene in tumor tissue were significantly higher compared to that in adjacent tissues (p<0.05). PSA gene and protein increased significantly with the clinical stage of TNM and decreased following the increase of grade (p<0.05). The miR-155 level was significantly elevated in the tumor tissue compared with para-carcinoma tissue (p<0.05). PSA and miR-155 expressions were positively correlated with TNM stage, tumor volume, and LNM, and negatively correlated with grade (p<0.05). PSA and miR-155 were closely related to the clinicopathological features of prostate cancer. Combined detection is helpful for the early diagnosis of prostate cancer.

Histomorphometry of feline chronic kidney disease and correlation with markers of renal dysfunction.

PubMed

Chakrabarti, S; Syme, H M; Brown, C A; Elliott, J

2013-01-01

Chronic kidney disease is common in geriatric cats, but most cases have nonspecific renal lesions, and few studies have correlated these lesions with clinicopathological markers of renal dysfunction. The aim of this study was to identify the lesions best correlated with renal function and likely mediators of disease progression in cats with chronic kidney disease. Cats were recruited through 2 first-opinion practices between 1992 and 2010. When postmortem examinations were authorized, renal tissues were preserved in formalin. Sections were evaluated by a pathologist masked to all clinicopathological data. They were scored semiquantitatively for the severity of glomerulosclerosis, interstitial inflammation, and fibrosis. Glomerular volume was measured using image analysis; the percentage of glomeruli that were obsolescent was recorded. Sections were assessed for hyperplastic arteriolosclerosis and tubular mineralization. Kidneys from 80 cats with plasma biochemical data from the last 2 months of life were included in the study. Multivariable linear regression (P < .05) was used to assess the association of lesions with clinicopathological data obtained close to death. Interstitial fibrosis was the lesion best correlated with the severity of azotemia, hyperphosphatemia, and anemia. Proteinuria was associated with interstitial fibrosis and glomerular hypertrophy, whereas higher time-averaged systolic blood pressure was associated with glomerulosclerosis and hyperplastic arteriolosclerosis.

Clinicopathological parameters associated with histological background and recurrence after surgical intervention of vocal cord leukoplakia.

PubMed

Cui, Weixin; Xu, Wen; Yang, Qingwen; Hu, Rong

2017-06-01

Histological examination of biopsy shows usefulness in the diagnosis of vocal cord leukoplakia; however, in considerable amount of cases, the examination cannot provide definitive diagnosis of malignancy from benign conditions such as hyperplasia and dysplasia. The present work therefore was aimed to identify clinicopathological factors and molecular markers predictive of recurrence and malignant transformation of vocal cord leukoplakia.Clinical data of 555 cases of vocal cord leukoplakia enrolled from July 1999 to June 2014 were analyzed. The cohort consisted of keratosis (n = 137), hyperplasia (n = 139), dysplasia (n = 177), and primary (n = 10) and invasive (n = 46) carcinoma. Correlations between patients' backgrounds, clinicopathological factors, molecular markers (p53, p16, Ki67, cytokeratin, and proliferating cell nuclear antigen), and histology backgrounds were examined using by Pearson Chi-squared or Fisher exact test. Reflux symptom index (RSI) and reflux finding score (RFS) before and after treatment were compared using Wilcoxon signed-rank test. Risk factors for disease recurrence were identified using Cox proportional hazards models of multivariate analysis. Time to recurrence was analyzed using log-rank test of Kaplan-Meier method.In the present cohort, alcohol drinking was found associated with GRBAS grade (P = .0258) and the site (P = .0298) of leukoplakia. For the different disease types, chief complaint (P = .0179), GRBAS grade (P = .0101), mucosal wave (P < .0001), and molecular markers p53 (P < .0001) and Ki67 (P < .0001) were identified as correlates. RSI and RFS were significantly lowered by surgical intervention. A single side of leukoplakia was predictive of a lower risk of recurrence (odds ratio, 0.378; 95% confidence interval, 0.197-0.723; P = .0033). Absence of mucosal wave was associated with a shorter time-to-recurrence (P = .0357).The present work identified clinicopathological factors and molecular markers associated with the different histology of vocal cord leukoplakia, and also the prognostic factor for the low risk of recurrence after surgery.

Serum p53 antibody as a potential tumor marker in extrahepatic cholangiocarcinoma.

PubMed

Okada, Rei; Shimada, Hideaki; Otsuka, Yuichiro; Tsuchiya, Masaru; Ishii, Jun; Katagiri, Toshio; Maeda, Tetsuya; Kubota, Yoshihisa; Nemoto, Tetsuo; Kaneko, Hironori

2017-12-01

Only a few studies have evaluated the clinicopathological significance of the p53 protein expression and s-p53-Abs level in patients with cholangiocarcinoma. We therefore analyzed the clinicopathological and prognostic significance of s-p53-Abs in patients with extrahepatic cholangiocarcinoma. We prospectively evaluated s-p53-Abs levels before and after surgery in 61 patients with extrahepatic cholangiocarcinoma to determine the relationship between clinicopathological factors and the prognostic significance of s-p53-Abs. Among a total of 61 primary extrahepatic cholangiocarcinoma cases, 23% were positive for s-p53-Abs. Combination of s-p53-Abs with the conventional serum markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) significantly increased the rate of positive extrahepatic cholangiocarcinoma cases (57% for CEA and/or CA19-9 vs. 75% for CEA and/or CA19-9 and/or s-p53-Abs, P = 0.035). There were no significant differences in clinicopathological factors between the p53-seropositive and p53-seronegative patients. An immunohistochemical analysis showed the presence of significant associations between the intensity (P = 0.003) and extent (P = 0.001) of p53 immunoreactivity and p53-seropositivitly. Although s-p53-Abs was not a significant prognostic factor for the survival in either univariate or multivariate analyses, p53 immunoreactivity was independently associated with a poor survival. Among patients positive for s-p53-Abs before surgery, the s-p53-Abs levels were reduced after surgery in most. These findings suggested that s-p53-Abs might be associated with p53 immunoreactivity. In addition, s-p53-Abs may be useful for a diagnosis, but was not useful for predicting tumor recurrence or the survival. This study was registered as UMIN000014530.

Clinicopathological characteristics of duodenal epithelial neoplasms: Focus on tumors with a gastric mucin phenotype (pyloric gland-type tumors).

PubMed

Mitsuishi, Takehiro; Hamatani, Shigeharu; Hirooka, Shinichi; Fukasawa, Nei; Aizawa, Daisuke; Hara, Yuko; Dobashi, Akira; Goda, Kenichi; Fukuda, Takahiro; Saruta, Masayuki; Urashima, Mitsuyoshi; Ikegami, Masahiro

2017-01-01

Epithelial tumors less commonly occur in the duodenum than in the stomach or large intestine. The clinicopathological characteristics of duodenal epithelial tumors remain a matter of debate. We therefore studied resected specimens to investigate the clinicopathological characteristics of duodenal epithelial tumors. Among duodenal epithelial tumors resected endoscopically or surgically in our hospital, we studied the clinicopathological characteristics of 110 adenomas or intramucosal carcinomas. The grade of atypia of all tumors was classified into 3 groups according to the World Health Organization (WHO) 2010 classification. The tumors were immunohistochemically evaluated to determine the frequency of differentiation toward fundic glands. As for patient characteristics, there were 76 men (75.2%) and 25 women (24.8%), with a median age of 65 years (range, 34 to 84). The tumors most commonly arose in the first to second part of the duodenum. Many lesions were flat, and the median tumor diameter was 8.0 mm. The lesions were classified into 2 types according to mucin phenotype: intestinal-type tumors (98 lesions, 89.1%) and gastric-type tumors (12 lesions, 10.9%). Intestinal-type tumors were subdivided into 2 groups: tubular-type tumors (91 lesions, 82.7%) and tubulovillous-type tumors (7 lesions, 6.4%). Gastric-type tumors were classified into 2 types: foveolar type (3 lesions, 2.7%) and pyloric gland-type (PG) tumors (9 lesions, 8.2%). The grade of atypia was significantly higher in gastric-type tumors (p<0.01). PG tumors were gastric-type tumors characterized by pyloric glands and findings suggesting differentiation toward fundic glands. About 10% of the duodenal tumors had a gastric-type mucin phenotype. Gastric-type tumors showed high-grade atypia. In particular, PG tumors showed similarities to PG tumors of the stomach, such as differentiation toward fundic glands.

Clinicopathological factors predictive of postoperative seizures in patients with gliomas.

PubMed

Yang, Pei; Liang, Tingyu; Zhang, Chuanbao; Cai, Jinquan; Zhang, Wei; Chen, Baoshi; Qiu, Xiaoguang; Yao, Kun; Li, Guilin; Wang, Haoyuan; Jiang, Chuanlu; You, Gan; Jiang, Tao

2016-02-01

Epilepsy is one of the most common manifestations in gliomas and has a severe effect on the life expectancy and quality of life of patients. The aim of our study was to assess the potential connections between clinicopathological factors and postoperative seizure. We retrospectively investigated a group of 147 Chinese high-grade glioma (HGG) patients with preoperative seizure to examine the correlation between postoperative seizure and clinicopathological factors and prognosis. Univariate analyses and multivariate logistic regression analyses were performed to identify factors associated with postoperative seizures. Survival function curves were calculated using the Kaplan-Meier method. 53 patients (36%) were completely seizure-free (Engel class I), and 94 (64%) experienced a postoperative seizure (Engel classes II, III, and IV). A Chi-squared analysis showed that anaplastic oligodendroglioma/anaplastic oligoastrocytoma (AO/AOA) (P=0.05), epidermal growth factor receptor (EGFR) expression (P=0.0004), O(6)-methylguanine DNA methyltransferase (MGMT) expression (P=0.011), and phosphatase and tensin homolog (PTEN) expression (P=0.045) were all significantly different. A logistic regression analysis showed that MGMT expression (P=0.05), EGFR expression (P=0.001), and AO/AOA (P=0.038) are independent factors of postoperative seizure. Patients with lower MGMT and EGFR expression and AO/AOA showed more frequent instances of postoperative seizure. Postoperative seizure showed no statistical significance on overall survival (OS) and progression-free survival (PFS). Our study identified clinicopathological factors related to postoperative seizure in HGGs and found two predictive biomarkers of postoperative seizure: MGMT and EGFR. These findings provided insight treatment strategies aimed at prolonging survival and improving quality of life. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Aberrant Expression of Calretinin, D2-40 and Mesothelin in Mucinous and Non-Mucinous Colorectal Carcinomas and Relation to Clinicopathological Features and Prognosis.

PubMed

Foda, Abd AlRahman Mohammad; El-Hawary, Amira Kamal; Hamed, Hazem

2016-10-01

CRC is a heterogeneous disease in terms of morphology, invasive behavior, metastatic capacity, and clinical outcome. Recently, many so-called mesothelial markers, including calretinin, D2-40, WT1, thrombomodulin, mesothelin, and others, have been certified. The aim of this study was to assess the immunohistochemical expression of calretinin and other mesothelial markers (D2-40 and mesothelin) in colorectal mucinous adenocarcinoma (MA) and non mucinous adenocarcinoma (NMA) specimens and relation to clinicopathological features and prognosis using manual tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal MA and NMA who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using Calretinin, D2-40 and mesothelin expressions. We found that NMA showed significantly more calretinin and D2-40 expression than MA In contrast, no statistically significant difference between NMA and MA was detected in mesothelin expression. There were no statistically significant relations between any of the clinicopathological or histological parameters and any of the three markers. In a univariate analysis, neither calretinin nor D2-40 expressions showed any significant relations to DFS or OS. However, mesothelin luminal expression was significantly associated with worse DFS. Multivariate Cox regression analysis proved that luminal mesothelin expression was an independent negative prognostic factor in NMA. In conclusion, Calretinin, D2-40 and mesothelin are aberrantly expressed in a proportion of CRC cases with more expression in NMA than MA. Aberrant expression of these mesothelial markers was not associated with clinicopathological or histological features of CRCs. Only mesothelin expression appears to be a strong predictor of adverse prognosis.

Overexpression of Cyclooxygenase-2 and Transforming Growth Factor-Beta 1 is an Independent Predictor of Poor Virological Response to Interferon Therapy in Chronic HCV Genotype 4 Patients

PubMed Central

Gomaa, Wafaey M.; Ibrahim, Mohammed A.; Shatat, Mohamed E.

2014-01-01

Background/Aims: COX-2 and TGF-β1 are overexpressed in hepatitis C virus (HCV) infection and are related to hepatitis pathogenesis and hepatic fibrosis. The current study investigated the relationship between pretreatment COX-2 and TGF-β1 hepatic expression in HCV genotype 4 and the virological response to interferon therapy. Patients and Methods: Liver biopsies of 55 patients with HCV infection genotype 4 were selected together with 10 liver biopsies as control. The patients’ clinicopathological data were collected. Immunohistochemistry was done using anti-COX-2 and anti-TGF-β1 antibodies. Statistical tests were used to determine the association between both COX-2 and TGF-β1 expression in relation to clinicopathological parameters and response to interferon therapy. Results: COX-2 was upregulated especially in nonresponders and was an independent predictor of poor virological response. However, COX-2 showed no association with other clinicopathological features. TGF-β1 was upregulated and associated with nonresponders, histological activity, and fibrosis stage. There was no association between TGF-β1 and other clinicopathological features. There was an association between COX-2 and TGF-β1 immunoexpression. Conclusion: Overexpression of COX-2 and TGF-β1 is an independent predictor for poor outcome of interferon and ribavirin therapy and these might be useful markers for the response to treatment. Both molecules are associated together; however, their role during hepatitis treatment has to be clarified. PMID:24496160

Prevalence and clinicopathological characteristics of ALK fusion subtypes in lung adenocarcinomas from Chinese populations.

PubMed

Zheng, Difan; Wang, Rui; Zhang, Yang; Pan, Yunjian; Cheng, Xinghua; Cheng, Chao; Zheng, Shanbo; Li, Hang; Gong, Ranxia; Li, Yuan; Shen, Xuxia; Sun, Yihua; Chen, Haiquan

2016-04-01

We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations. We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients. Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10-2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4-ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas. ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses.

The Warthin-Like Variant of Papillary Thyroid Carcinoma: A Comparison with Classic Type in the Patients with Coexisting Hashimoto's Thyroiditis.

PubMed

Yeo, Min-Kyung; Bae, Ja Seong; Lee, Sohee; Kim, Min-Hee; Lim, Dong-Jun; Lee, Youn Soo; Jung, Chan Kwon

2015-01-01

Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear. Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC. BRAF mutation was tested with pyrosequencing. Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto's thyroiditis than classic PTCs (93% versus 36%, resp., P < 0.001) and showed significantly lower rate of BRAF mutation when compared to classic PTCs (65% versus 84%, resp., P = 0.007). In classic PTC, the frequency of BRAF mutations was negatively correlated with coexisting Hashimoto's thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto's thyroiditis, there were no significant differences in clinicopathologic characteristics or the BRAF mutational rate between the two groups. Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto's thyroiditis.

The Warthin-Like Variant of Papillary Thyroid Carcinoma: A Comparison with Classic Type in the Patients with Coexisting Hashimoto's Thyroiditis

PubMed Central

Yeo, Min-kyung; Bae, Ja Seong; Lim, Dong-Jun; Lee, Youn Soo

2015-01-01

Background. The Warthin-like variant of papillary thyroid (WLPTC) is a rare subtype of papillary thyroid carcinoma (PTC) resembling Warthin tumors of the salivary glands. Due to its rarity, the clinicopathologic and molecular features of WLPTC remain unclear. Methods. Of the 2,139 patients who underwent surgical treatment for PTC from 2012 to 2013, 40 patients with WLPTC were identified and compared to 200 consecutive patients with classic PTC. BRAF mutation was tested with pyrosequencing. Results. There were no significant differences in age, predilection for women, multifocality, extrathyroidal extension, or lymph node metastasis between WLPTC and classic PTC. However, WLPTCs were more commonly associated with Hashimoto's thyroiditis than classic PTCs (93% versus 36%, resp., P < 0.001) and showed significantly lower rate of BRAF mutation when compared to classic PTCs (65% versus 84%, resp., P = 0.007). In classic PTC, the frequency of BRAF mutations was negatively correlated with coexisting Hashimoto's thyroiditis. When we compared WLPTC and classic PTC in the patients with coexisting Hashimoto's thyroiditis, there were no significant differences in clinicopathologic characteristics or the BRAF mutational rate between the two groups. Conclusions. Patients with WLPTC have similar demographic, clinical, pathologic, and molecular characteristics to those with classic PTC coexisting with Hashimoto's thyroiditis. PMID:25983754

Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast.

PubMed

Min, Kyueng-Whan; Kim, Dong-Hoon; Do, Sung-Im; Chae, Seoung Wan; Kim, Kyungeun; Sohn, Jin Hee; Lee, Hyun Joo; Do, In-Gu; Pyo, Jung-Soo; Kim, Yuil; Kim, Dong Hyun; Yang, Jung-Ho; Lee, Sang-Jo; Oh, Young Ha; Oh, Sukjoong; Choi, Seon Hyeong; Park, Yong Lai; Park, Chan Heun; Kim, Eun-Kyung; Kwon, Mi Jung; Seo, Jinwon

2017-01-01

Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer. The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed. Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+. Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer. © 2017 S. Karger AG, Basel.

Leiomyosarcoma: One disease or distinct biologic entities based on site of origin?

PubMed

Worhunsky, David J; Gupta, Mihir; Gholami, Sepideh; Tran, Thuy B; Ganjoo, Kristen N; van de Rijn, Matt; Visser, Brendan C; Norton, Jeffrey A; Poultsides, George A

2015-06-01

Leiomyosarcoma (LMS) can originate from the retroperitoneum, uterus, extremity, and trunk. It is unclear whether tumors of different origin represent discrete entities. We compared clinicopathologic features and outcomes following surgical resection of LMS stratified by site of origin. Patients with LMS undergoing resection at a single institution were retrospectively reviewed. Clinicopathologic variables were compared across sites. Survival was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses. From 1983 to 2011, 138 patients underwent surgical resection for LMS. Retroperitoneal and uterine LMS were larger, higher grade, and more commonly associated with synchronous metastases. However, disease-specific survival, recurrence-free survival, and recurrence patterns were not significantly different across the four sites. Synchronous metastases (HR 3.20, P < 0.001), but not site of origin, size, grade, or margin status, were independently associated with worse DSS. A significant number of recurrences and disease-related deaths were noted beyond 5 years. Although larger and higher grade, retroperitoneal and uterine LMS share similar survival and recurrence patterns with their trunk and extremity counterparts. LMS of various anatomic sites may not represent distinct disease processes based on clinical outcomes. The presence of metastatic disease remains the most important prognostic factor for LMS. © 2015 Wiley Periodicals, Inc.

Comparative analysis between clinical outcomes of primary radical resection and second completion radical resection for T2 gallbladder cancer: single-center experience.

PubMed

Cho, Seong Yeon; Park, Sang-Jae; Kim, Seong Hoon; Han, Sung-Sik; Kim, Young-Kyu; Lee, Kwang-Woong

2010-07-01

Gallbladder (GB) cancer may be discovered incidentally by histopathologic examination following simple cholecystectomy. Incidental GB cancer > or =T2 or > or =N1 needs a second radical resection. It is a matter of concern whether the prognosis may be worse in patients with T2GB cancer who undergo a second radical resection than in those who undergo primary radical resection. Between March 2001 and March 2009, 21 patients underwent a one-step operation (OSO group), and 17 patients underwent a two-step operation (TSO group) for T2GB cancer. We compared clinicopathologic factors and survival between patients in the OSO group (n = 9) and those in the TSO group (n = 9) with T2N0M0 GB cancer and between patients in the OSO group (n = 12) and those in the TSO group (n = 8) with T2N1M0 GB cancer. Except for patient age, clinicopathologic factors as well as disease-free survival were not significantly different between the OSO group and the TSO group in the aforementioned cancer stages. Patient age was significantly higher in the OSO group than in the TSO group. Second completion radical resection following initial simple cholecystectomy (TSO) provided a survival benefit similar to that of primary radical surgery (OSO) for patients with both T2N0M0 and T2N1M0 GB cancers in our study.

Clinicopathologic Features of Polypoid Lesions of the Gallbladder and Risk Factors of Gallbladder Cancer

PubMed Central

Kwon, Wooil; Lee, Seung Eun; Hwang, Dae Wook; Kim, Sun-Whe

2009-01-01

It is difficult to differentiate benign and malignancy in polypoid lesions of the gallbladder (PLG) by solely depending on imaging studies. Therefore clinicopathologic features of benign and malignant polyps are compared in an attempt to identify the risk factors of malignant polypoid lesions. The medical records of 291 patients who were confirmed to have PLG through cholecystectomy were reviewed and analyzed for age, sex, symptom, associated gallstone, morphology of PLG, size of PLG, number of PLG, and preoperative tumor markers. Benign PLG was found in 256 patients (88.0%) and malignant PLG in 35 patients (12.0%). Compared with benign group, the malignant group were older (61.1 yr vs. 47.1 yr, P<0.001), more often accompanied with symptoms (62.9% vs. 28.9%, P<0.001). Malignant PLG tended to be sessile (60.0% vs. 10.5%, P<0.001), larger (28.0 mm vs. 8.6 mm, P<0.001) and single lesion (65.7% vs. 44.1%, P<0.016). Age over 60 yr (P=0.021, odds ratio [OR], 8.16), sessile morphology (P<0.001, OR, 7.70), and size over 10 mm (P=0.009, OR, 8.87) were identified as risk factors for malignant PLG. Careful decision making on therapeutic plans should be made with consideration of malignancy for patients over 60 yr, with sessile morphology of PLG, and with PLG size of over 10 mm. PMID:19543513

[Clinico-pathological features of papillary thyroid cancer coexistent with Hashimoto's thyroiditis].

PubMed

Molnár, Sarolta; Győry, Ferenc; Nagy, Endre; Méhes, Gábor; Molnár, Csaba

2017-02-01

Former studies suggest the frequent coexistence of Hashimoto's thyreoditis with papillary thyroid cancer, frequently featured by multifocal carcinogenesis but lower clinical stages compared to thyroid cancers lacking thyroiditis. We examined the clinico-pathological correlations between Hashimoto's thyroditis and papillary thyroid cancer in our region in the North-Eastern part of Hungary. We included a total of 230 patients with papillary thyroid cancer who underwent thyroid surgery at the Surgical Department of the University of Debrecen. Patients' sex, age, multifocality of thyroid cancer and clinical stage were evaluated. Cases included 40 patients (17.4%) with (4 male, 36 female) and 190 (82.6%) patients without HT (44 male, 146 female). Hashimoto's thyroiditis related thyroid cancer was almost exclusively associated with the papillary histological type. Multifocality of papillary cancer was significantly more frequent with coexisting Hashimoto's thyroiditis (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%; p = 0.034). In contrast, lymph node metastasis was significantly less frequent among patients with Hashimoto's thyroiditis (4 pN1 [36.4%]; 7 pN0 [63.6%]) then without it (34 pN1 [82.9%]; 7 pN0 [17.1%]; p = 0.002). Higher frequency and multifocality of papillary thyroid cancer might be the consequence of preexisting Hashimoto's thyroiditis to be considered as a preneoplastic stimulus supporting carcinogenesis, though the exact pathomechanism of this correlation is not clear yet. Orv. Hetil., 2017, 158(5), 178-182.

The prevalence and clinicopathological profile of IgM nephropathy in children with steroid-resistant nephrotic syndrome at a single centre in Pakistan.

PubMed

Shakeel, Shaheera; Mubarak, Muhammed; Kazi, Javed I; Lanewala, Ali

2012-12-01

There is little information on the clinicopathological characteristics of IgM nephropathy (IgMN) in paediatric steroid-resistant nephrotic syndrome (SRNS) and its response to calcineurin inhibitors (CNI). This study was conducted at Sindh Institute of Urology and Transplantation, from January 2009 to August 2011. All SRNS children who received renal biopsies were included. Relevant data were compared among minimal change disease (MCD) and IgMN. The response to CNI was analysed in detail in IgMN by groups (group 1: complete or partial remission; group 2: no response). The frequency of IgMN in 147 children with SRNS was 13.6%. Compared with MCD, there was a male preponderance in IgMN. Blood urea and serum creatinine both at presentation and at last follow-up were significantly higher in IgMN. Regarding subgroups of IgMN, systolic blood pressure (SBP), blood urea and serum creatinine were significantly higher in group 2 at presentation, while at last follow-up, SBP, diastolic blood pressure and proteinuria were higher in group 2. The prevalence and degree of mesangial proliferation, global glomerulosclerosis, interstitial fibrosis and tubular atrophy were significantly higher in group 2. IgMN is a common cause of paediatric SRNS and is significantly different from MCD. There is also a significant difference in clinical and laboratory parameters among responders and non-responders to CNI in IgMN.

Orbital angiogenesis and lymphangiogenesis in thyroid eye disease: an analysis of vascular growth factors with clinical correlation

PubMed Central

Wong, Lindsay L.; Lee, Nahyoung Grace; Amarnani, Dhanesh; Choi, Catherine J.; Bielenberg, Diane R.; Freitag, Suzanne K.; D’Amore, Patricia A.; Kim, Leo A.

2017-01-01

Purpose The human orbit is an environment that is vulnerable to inflammation and edema in the setting of autoimmune thyroid disease. Our study investigated the tenet that orbital adipose tissue lacks lymphatic vessels and analyzed the clinicopathologic differences between patients with acute and chronic thyroid eye disease (TED). The underlying molecular mediators of blood and lymphatic vessel formation within the orbital fat were also evaluated. Design Retrospective cohort study Participants The study included fat specimens from 26 orbits of 15 patients with TED undergoing orbital decompression. Orbital fat specimens from patients without TED as well as cadaveric orbital fat served as controls. Methods Tissue specimens were processed as formalin-fixed paraffin-embedded sections (FFPE) or frozen cryosections for immunohistochemistry. Total RNA was extracted and analyzed via quantitative (real-time) reverse transcription polymerase chain reaction (qRT-PCR). Clinicopathological correlation was made by determining the Clinical Activity Score (CAS) of each patient with TED. Main Outcome Measures Samples were examined for vascular and lymphatic markers including podoplanin, LYVE-1, and CD31 by immunohistochemistry, as well as for mRNA levels of VEGF, VEGF receptors, SEMA-3F, NRP-1, NRP-2, podoplanin and LYVE-1 by qRT-PCR. Results Clinicopathological correlation revealed increased staining of CD31-positive blood vessels in patients with acute TED with CAS > 4, as well as rare staining of podoplanin-positive lymphatic vessels within acutely inflamed orbital fat tissue. Additionally, qRT-PCR analysis demonstrated increased expression of vascular endothelial growth factor receptor 2 (VEGFR-2) as well as VEGF signaling molecules: VEGF-A, VEGF-C, and VEGF-D. Conclusions In acute TED, compared to chronic TED and control orbital fat, there is increased blood vessel density suggesting neovascularization and rare lymphatic vessels suggestive of limited lymphangiogenesis. This pro-angiogenic and pro-lymphangiogenic microenvironment is likely due to the increased expression of VEGFR-2 and VEGF-A, VEGF-C, and VEGF-D. These findings imply that orbital edema in acute TED may be mediated, in part, by both the formation of new, immature blood vessels and the formation of lymphatic capillaries that are functionally incapable of draining interstitial fluid. PMID:27423310

[Central nervous system dysgerminoma: a clinicopathological study of 3 cases].

PubMed

Bellil, Selma; Braham, Emna; Limaiem, Faten; Bellil, Khadija; Chelly, Ines; Mekni, Amina; Haouet, Slim; Zitouna, Moncef; Jemel, Hafedh; Khaldi, Moncef; Kchir, Nidhameddine

2009-03-01

Intracranial germ cell tumors are rarely seen and typically localize in the pineal or suprasellar region. The largest category of germ cell tumors is dysgerminoma. to describe clinicopathological features and immunohistochemical profile of dysgerminomas. We report three cases of central nervous system dysgerminomas. There were two young women and a man who were 6, 11 and 23-year-old. They presented with symptoms of insipidus diabetes (n=3) with association to visual field defects in the third case. Radiological findings showed a supra seller lesion in two cases. Double localization in the pineal and suprasellar regions was seen in the third case. Histologic examination and immunohistochemical study of surgical specimen were consistent with primary central nervous system dysgerminoma.

The low expression of miR-451 predicts a worse prognosis in non-small cell lung cancer cases.

PubMed

Goto, Akiteru; Tanaka, Masamitsu; Yoshida, Makoto; Umakoshi, Michinobu; Nanjo, Hiroshi; Shiraishi, Kouya; Saito, Motonobu; Kohno, Takashi; Kuriyama, Sei; Konno, Hayato; Imai, Kazuhiro; Saito, Hajime; Minamiya, Yoshihiro; Maeda, Daichi

2017-01-01

miR-451 is a tumor suppressive microRNA with several target genes, including Macrophage migration inhibitory factor (MIF). As little is known about the expression and clinicopathological significance of mir-451 in NSCLC, we performed a clinicopathological study of 370 NSCLC cases to clarify them. Cell biological experiments were also performed on NSCLC cell lines to confirm the tumor-suppressive role of miR-451 and whether or not MIF is targeted by miR-451. We analyzed 370 NSCLC cases for the miR-451 expression by quantitative real-time polymerase chain reaction and the MIF expression by immunohistochemistry. Eighty-four background lung tissue samples were also evaluated for the miR-451 expression. The clinicopathological and genetic factors surveyed were the disease-free survival, smoking status, histological type, disease stage, EGFR gene mutations and ALK rearrangements. In 286 adenocarcinoma cases, the invasive status (adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma) was also evaluated. Five NSCLC cell lines (H23, H441, H522, H1703, and H1975) were cultured and evaluated for their miR-451 and MIF expression. The cell lines with lower miR-451 and higher MIF expressions were then selected and transfected with miR-451-mimic to observe its effects on MIF expression, Akt and Erk status, cell proliferation, and cell migration. The miR-451 expression was down-regulated in cancer tissues compared with background lung tissues (P<0.0001). Factors such as advanced disease stage, positive pleural invasion and nodal status and being a smoker were significantly correlated with a lower expression of miR-451 (P<0.05 each), while EGFR gene mutations and ALK rearrangements were not. In adenocarcinoma, invasive and minimally invasive adenocarcinoma showed lower expression of miR-451 than adenocarcinoma in situ (P<0.0005, respectively). A survival analysis showed that a lower expression of miR-451 was an independent predictor of a poor prognosis for NSCLC (P<0.05). The MIF expression was inversely correlated with the miR-451 expression. Out of 5 NSCLC cell lines examined, H441 and H1975 showed higher MIF and lower miR-451 expressions. After the transfection of miR-451-mimic, the MIF expression and phosphorylated Akt expression of these cell lines was suppressed, as were cell proliferation and cell migration. This clinicopathological study of 370 NSCLC cases and the cell biological studies of NSCLC cell lines clarified the tumor-suppressive role of miR-451 and its prognostic value. We also validated MIF as a target of miR-451 in NSCLC.

Comparison of clinicopathologic features and survival of histopathologically amelanotic and pigmented melanomas: a population-based study.

PubMed

Thomas, Nancy E; Kricker, Anne; Waxweiler, Weston T; Dillon, Patrick M; Busman, Klaus J; From, Lynn; Groben, Pamela A; Armstrong, Bruce K; Anton-Culver, Hoda; Gruber, Stephen B; Marrett, Loraine D; Gallagher, Richard P; Zanetti, Roberto; Rosso, Stefano; Dwyer, Terence; Venn, Alison; Kanetsky, Peter A; Orlow, Irene; Paine, Susan; Ollila, David W; Reiner, Anne S; Luo, Li; Hao, Honglin; Frank, Jill S; Begg, Colin B; Berwick, Marianne

2014-12-01

IMPORTANCE Previous studies have reported that histopathologically amelanotic melanoma is associated with poorer survival than pigmented melanoma; however, small numbers of amelanotic melanomas, selected populations, lack of centralized pathologic review, or no adjustment for stage limit the interpretation or generalization of results from prior studies.OBJECTIVE To compare melanoma-specific survival between patients with histopathologically amelanotic and those with pigmented melanoma in a large international population-based study.DESIGN, SETTING, AND PARTICIPANTS Survival analysis with a median follow-up of 7.6 years.The study population comprised 2995 patients with 3486 invasive primary melanomas centrally scored for histologic pigmentation from the Genes, Environment, and Melanoma(GEM) Study, which enrolled incident cases of melanoma diagnosed in 1998 through 2003 from international population-based cancer registries.MAIN OUTCOMES AND MEASURES Clinicopathologic predictors and melanoma-specific survival of histologically amelanotic and pigmented melanoma were compared using generalized estimating equations and Cox regression models, respectively.RESULTS Of 3467 melanomas, 275 (8%) were histopathologically amelanotic. Female sex,nodular and unclassified or other histologic subtypes, increased Breslow thickness, presence of mitoses, severe solar elastosis, and lack of a coexisting nevus were independently associated with amelanotic melanoma (each P < .05). Amelanotic melanoma was generally ofa higher American Joint Committee on Cancer (AJCC) tumor stage at diagnosis (odds ratios[ORs] [95%CIs] between 2.9 [1.8-4.6] and 11.1 [5.8-21.2] for tumor stages between T1b and T3b and ORs [95%CIs] of 24.6 [13.6-44.4] for T4a and 29.1 [15.5-54.9] for T4b relative to T1a;P value for trend, <.001) than pigmented melanoma. Hazard of death from melanoma was higher for amelanotic than for pigmented melanoma (hazard ratio [HR], 2.0; 95%CI, 1.4-3.0)(P < .001), adjusted for age, sex, anatomic site, and study design variables, but survival did not differ once AJCC tumor stage was also taken into account (HR, 0.8; 95%CI, 0.5-1.2)(P = .36).CONCLUSIONS AND RELEVANCE At the population level, survival after diagnosis of amelanotic melanoma is poorer than after pigmented melanoma because of its more advanced stage at diagnosis. It is probable that amelanotic melanomas present at more advanced tumor stages because they are difficult to diagnose. The association of amelanotic melanoma with presence of mitoses independently of Breslow thickness and other clinicopathologic characteristics suggests that amelanotic melanomas might also grow faster than pigmented melanomas. New strategies for early diagnosis and investigation of the biological properties of amelanotic melanoma are warranted.

Clinicopathological characteristics and survival outcomes in pleomorphic lobular breast carcinoma of the breast: a SEER population-based study.

PubMed

Yang, Li-Peng; Sun, He-Fen; Zhao, Yang; Chen, Meng-Ting; Zhang, Nong; Jin, Wei

2017-12-01

The purpose of this study was to explore the clinicopathological features and survival outcome of pleomorphic lobular carcinoma (PLC) of breast, we identified 131 PLC patients and 460,109 invasive ductal carcinoma (IDC) patients in the Surveillance, Epidemiology, and End Result (SEER) database. PLCs presented with increased lymph node involvement, older age, higher AJCC stage and grade, and lower median survival months (PLC 84 ± 51.03 vs. IDC 105.2 ± 64.39 P < 0.01). Compared to IDC patients, PLC patients were more inclined to be treated with mastectomy. In univariate analysis, PLC patients showed a worse disease-specific survival (DSS) than that of IDC patients (hazard ratio = 0.691, 95% confidence interval 0.534-0.893, P < 0.01). In multivariate analysis, we took into account other prognostic factors and found that the histology types were no longer an independent prognostic factor (P = 0.120). DSS have no difference between matched IDC and PLC groups (P = 0.615). This result may be due to PLCs presenting higher tumor stage, higher tumor grade, and higher rate of LN metastasis than IDCs. Our conclusion is that PLC and IDC have many different characteristics, but there is not enough difference on the DSS. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Reduced miR-300 expression predicts poor prognosis in patients with laryngeal squamous cell carcinoma.

PubMed

He, F-Y; Liu, H-J; Guo, Q; Sheng, J-L

2017-02-01

miR-300 has been demonstrated to play an important role in the progression of several tumors, but its role in tumorigenesis of laryngeal squamous cell carcinoma (LSCC) is still unclear. The purpose of this study was to explore miR-300 expression in LSCC patients and analyze its association with clinicopathological factors and prognosis. In the present study, we measured the expression level of miR-300 in LSCC tissues by RT-PCR. Associations between miRNA-300 expressions and various clinicopathological characteristics were analyzed. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. The univariate and multivariate analysis were performed using the Cox proportional hazard analysis. miR-300 expression was significantly increased in LSCC tissues compared with that in adjacent non-cancerous tissues (p < 0.01). In addition, lymph node metastasis (p = 0.004) and TNM stage (p = 0.001) were obvious influence factors for the expression of miR-300. More importantly, Kaplan-Meier analysis showed that LSCC patients with low miR-300 expression tended to have shorter overall survival (p < 0.001). Finally, multivariate analysis revealed that miR-300 expression was an independent prognostic factor for LSCC patients. Our results pointed to miR-300 as a powerful prognostic marker in LSCC and as a novel target for tumor-suppressive therapy.

Melanoma of the vulva and vagina: principles of staging and their relevance to management based on a clinicopathologic analysis of 85 cases.

PubMed

Seifried, Susan; Haydu, Lauren E; Quinn, Michael J; Scolyer, Richard A; Stretch, Jonathan R; Thompson, John F

2015-01-01

Primary melanomas of the vulva and vagina are rare. As a result, it has been difficult to develop evidence-based guidelines for their management. By analyzing a large series of patients with vulval and vaginal melanomas, this study sought to document the most common presenting features, identify clinical and pathologic predictors of outcome, and provide management guidelines. A clinicopathologic analysis of 85 patients with primary melanomas of the vulva or vagina diagnosed and treated at Melanoma Institute Australia and associated units in Sydney, Australia, between 1960 and 2011 was performed. Predictors of disease-free and melanoma-specific survival (MSS) were determined. Patients with American Joint Committee on Cancer (AJCC) stage 0-II had a significantly better MSS (5Y MSS = 63.6 %, n = 59) compared with those with stage III disease (5Y MSS = 0 %, n = 12, p < 0.001). Tumor thickness, ulceration status, and pathologic clearance margin were significant predictors of MSS. Disease-free survival was predicted by these factors and additionally by tumor mitotic rate. The results of this study provide evidence to support the appropriateness of utilizing the AJCC (7th edition) cutaneous melanoma staging system for vulval and vaginal melanomas. Detection and removal of these melanomas at an early stage with pathologically confirmed clear margins confers the best chance of cure.

Nevus-associated melanomas: clinicopathologic features.

PubMed

Shitara, Danielle; Nascimento, Mauricio M; Puig, Susana; Yamada, Sérgio; Enokihara, Milvia M S S; Michalany, Nilceo; Bagatin, Ediléia

2014-10-01

The clinical significance of nevus-associated melanoma compared with de novo melanomas remains controversial. It has been suggested that nevus-associated melanomas have a higher Breslow thickness and therefore worse prognosis. Over a 10-year period, this study evaluated the incidence of nevus-associated melanoma and its prognostic significance related to clinicopathologic features. Cross-sectional study from 1995 through 2004 in a dermatopathology referral center. With available data, we evaluated sex, primary location, histologic subtype, Breslow thickness, Clark level, presence of ulceration, associated lesion, and histologic subtype of the associated lesion. Of 135,653 pathologic records from skin biopsy specimens over a 10-year period, 1,190 melanoma records were selected. Nevus-associated melanomas corresponded to 390 (32.8%) melanomas, with thin melanomas having a nevus 1.52 times the association observed with thick melanomas (>1.01 mm; 95% confidence interval, 1.16-1.99; P < .001). Superficial spreading melanoma was the most frequent, while no lentigo maligna melanoma was associated with nevi. The median Breslow thickness of nevus-associated melanomas was lower than that of de novo melanomas. Nevus-associated melanomas, which represent one-third of the melanomas in southeast Brazil, are associated with intermittent sun exposure, superficial spreading melanomas, and lower Breslow thickness. This is one of the largest series describing nevus-associated melanomas in Latin America. Copyright© by the American Society for Clinical Pathology.

Comparison of the clinicopathological features of flat and polypoid colorectal adenomas that are smaller than or equal to five millimeters.

PubMed

Yener, Neşe Arzu; Midi, Ahmet; Ataizi Çelikel, Ciğdem

2014-02-01

Colorectal flat adenomas (FAs) may represent a different histogenesis, since their malignant potential is thought to be higher than polypoid adenomas of the same size. In this study, we classified FAs of ≤5 mm into three subgroups-superficially elevated adenomas (SEAs), completely flat adenomas (CFAs), and depressed adenomas (DAs)-based on their low microscopic shapes and compared their clinicopathological features with polypoid tubular adenomas (pTAs) with the same size. One hundred one pTAs and 46 FAs with tubular morphology with the same size (≤5 mm) were studied. The percentages of high-grade dysplasia in FAs and pTAs were 19.56% and 12.87%, respectively. The percentages of the high-grade dysplasia were 28.57%, 13.63%, and 20.00% in the DA, SEA, and CFA subgroups, respectively. FAs had a significantly higher number of normal epithelium at the basal crypts of the lesion than the pTAs (p=0.001). The presence of pericryptal mesenchymal cells was higher in pTAs than the FAs (78.21% vs 10.86%) (p<0.001). Flat adenoma represents a distinct type of colorectal adenoma with special histopathological properties-existence of a normal epithelium at the basal crypts, lack of pericryptal mesenchymal cells, and a high percentage of high-grade dysplasia-especially when it has a depressed shape at low magnification.

Clinicopathological Factors Affecting Survival and Recurrence after Initial Hepatectomy in Non-B Non-C Hepatocellular Carcinoma Patients with Comparison to Hepatitis B or C Virus

PubMed Central

Shiraishi, Taizou; Murata, Yasuhiro; Tanemura, Akihiro; Azumi, Yoshinori; Kuriyama, Naohisa; Kishiwada, Masashi; Usui, Masanobu; Tabata, Masami; Yamada, Tomomi

2014-01-01

We evaluated clinicopathological factors affecting survival and recurrence after initial hepatectomy in non-B non-C (NBNC) hepatocellular carcinoma (HCC) patients with comparison to hepatitis B or C virus, paying attention to relationship between alcohol consumption and histopathological findings. The medical records on the 201HCC patients who underwent initial hepatectomy between January 2000 and April 2013 were retrospectively reviewed. NBNC patients had higher prevalence of hypertension (47.4%), diabetes mellitus (35.5%), alcohol consumption (>20 g/day) (61.8%), and preserved liver function than hepatitis B or C patients. The 5-year survival rate of NBNC patients (74.1%) was significantly better than hepatitis B (49.1%) or C (65.0%) patients (NBNC versus B, P = 0.031). Among the NBNC patients, there was no relationship between alcohol consumption and clinicopathological findings including nonalcoholic fatty liver disease activity score (NAS). However, the 5-year OS and RFS rates in the alcohol-unrelated NBNC patients tend to be better than in the alcohol-related. By multivariate analysis, independent factors for OS in NBNC patients were Child-Pugh B/C, intrahepatic metastasis (im), and extrahepatic recurrence. NBNC patients, who were highly associated with lifestyle-related disease and preserved liver function, had significantly better prognosis compared to hepatitis B/C patients; however, there was no association between alcohol consumption and histopathological findings. PMID:24745029

Clinicopathological Diversity of Canine Mammary Gland Tumors in Sri Lanka: A One-Year Survey on Cases Presented to Two Veterinary Practices.

PubMed

Ariyarathna, Harsha; de Silva, Niranjala; Aberdein, Danielle; Kodikara, Dayananda; Jayasinghe, Manjula; Adikari, Ranjith; Munday, John S

2018-04-27

Mammary gland tumors (MGTs) are one of the most common neoplasms among dogs in Sri Lanka. However, the clinicopathological diversity of MGTs in Sri Lanka is largely unknown, impeding accurate diagnosis and effective treatment of the disease. The present study investigated the clinicopathological features of MGTs in 74 dogs presented to two veterinary practices in Sri Lanka treated surgically, over a one-year period. Information regarding the patient signalment, clinical presentation, and reproductive history were collected, and each neoplasm was examined histologically. Forty-one (54.4%) dogs were primarily presented for mammary neoplasia, while a MGT was an incidental finding in 33 (44.6%) dogs. The majority of tumors were histologically malignant (n = 65, 87.8%), and 18 malignant tumor sub-types were identified. A significantly higher proportion of malignant tumors were large (>3 cm diameter) and observed in inguinal mammary glands. Nulliparous (n = 42, 55.3%) dogs predominated in the group, and the mean age of MGT diagnosis was 8.0 ± 2.41 years. The present study identified tumor location and size to be predictive of malignancy. A high histological diversity of MGTs was observed. Overall, the present findings emphasize the necessity of improving awareness of MGTs among Sri Lankan clinicians as well as dog owners.

[Granulomatous lobular mastitis associated with mammary duct ectasia: a clinicopathologic study of 32 cases with review of literature].

PubMed

Cheng, Juan; Ding, Hua-ye; DU, Yu-tang

2013-10-01

To study the clinicopathologic features of granulomatous lobular mastitis and mammary duct ectasia. The clinicopathologic data from August 2005 to May 2013 of 32 cases of granulomatous lobular mastitis and mammary duct ectasia were retrospectively reviewed. The age of patients ranged from 26 to 45 years. Two patients had no history of delivery. Fourteen patients had no history of lactation or lactational disorder in the lesional side. Most of the remaining patients had history of breast feeding. Gross examination showed that the lesions were poorly circumscribed and varied from 3 to 12 cm in greatest dimension. Tiny abscess cavities, ranging from 0.1 to 0.5 cm in diameter and containing light yellowish to greyish secretion, were demonstrated. Histologic examination showed granuloma formation and ductal dilatation. Eleven patients had received antibiotic treatment. Twelve cases were complicated by sinus formation related to skin incision and drainage. The duration of follow-up ranged from 5 to 90 months. Three cases showed ipsilateral recurrence and 3 cases had similar pathology in the contralateral breast. Four patients defaulted follow-up. Granulomatous lobular mastitis is associated with mammary duct ectasia. Accurate pathologic diagnosis is prudent for clinical management and control of local recurrence.

Alveolar ridge keratosis--a retrospective clinicopathological study.

PubMed

Bellato, Lorenzo; Martinelli-Kläy, Carla P; Martinelli, Celso R; Lombardi, Tommaso

2013-04-16

Alveolar ridge keratosis (ARK) is a distinct, benign clinicopathological entity, characterized by a hyperkeratotic plaque or patch that occurs on the alveolar edentulous ridge or on the retromolar trigone, considered to be caused by chronic frictional trauma. The aim of this retrospective study is to present the clinicopathological features of 23 consecutive cases of ARK. The 23 biopsy samples of ARK were selected and pathological features were revised (keratosis, acanthosis, surface architecture, and inflammation). Factors such as the patient's gender, age, anatomical location, tobacco and alcohol use were analyzed. Sixteen out of the 23 cases studied were men and 7 women with a mean age of 55.05 (age ranged from 17 to 88 years). Thirteen cases had a history of tobacco habit, amongst whom, 4 also presented alcohol consumption. All the cases presented only unilateral lesions. Nineteen cases involved the retromolar trigone while 4 cases involved edentulous alveolar ridges. When observed microscopically, the lesions were mainly characterized by moderate to important hyperorthokeratosis. Inflammation was scanty or absent. In four of the cases, the presence of melanin pigment in the superficial corium or in the cytoplasm of macrophages was detected. None of the cases showed any features of dysplasia. Our results reveal that ARK is a benign lesion. However, the high prevalence of smokers amongst the patients might suggest that some potentially malignant disorders such as tobacco associated leukoplakia may clinically mimic ARK.

Effect of infusion of equine plasma or 6% hydroxyethyl starch (600/0.75) solution on plasma colloid osmotic pressure in healthy horses.

PubMed

McKenzie, Erica C; Esser, Melissa M; McNitt, Sarah E; Payton, Mark E

2016-07-01

OBJECTIVE To compare the effects of equivalent volumes of equine plasma and 6% hydroxyethyl starch (600/0.75) solution (hetastarch) administered IV on plasma colloid osmotic pressure (pCOP) and commonly monitored clinicopathologic variables in horses. ANIMALS 6 healthy mares. PROCEDURES In a randomized, crossover study, horses were administered hetastarch or plasma (both 10 mL/kg, IV) 18 months apart. The pCOP and variables of interest were measured before (baseline), immediately after, and at intervals up to 96 or 120 hours after infusion. Prothrombin and activated partial thromboplastin times were measured before and at 2 and 8 hours after each infusion. RESULTS Prior to hetastarch and plasma infusions, mean ± SEM pCOP was 19.4 ± 0.5 mm Hg and 19.4 ± 0.8 mm Hg, respectively. In general, hetastarch and plasma infusions comparably increased pCOP from baseline for 48 hours, with maximum increases of 2.0 and 2.3 mm Hg, respectively. Mean Hct and hemoglobin, total protein, and albumin concentrations were decreased for a period of 72, 96, or 120 hours after hetastarch infusion with maximum decrements of 8.8%, 3.2 g/dL, 1.2 g/dL, and 0.6 g/dL, respectively. Plasma infusion decreased (albeit not always significantly) hemoglobin concentration and Hct for 20 and 24 hours (maximum changes of 1.5 g/dL and 6.6%, respectively) and increased total solids concentration (maximum change of 0.6 g/dL) for 48 hours. Platelet count and coagulation times were minimally affected. CONCLUSIONS AND CLINICAL RELEVANCE Overall, the hetastarch and plasma infusions comparably increased pCOP in healthy horses for up to 48 hours. Hetastarch induced greater, more persistent perturbations in clinicopathologic variables.

Statin Use and Serum Lipid Levels Are Associated With Survival Outcomes After Surgery for Renal Cell Carcinoma.

PubMed

Haddad, Ahmed Q; Jiang, Lai; Cadeddu, Jeffrey A; Lotan, Yair; Gahan, Jeffrey C; Hynan, Linda S; Gupta, Neil; Raj, Ganesh V; Sagalowsky, Arthur I; Margulis, Vitaly

2015-12-01

To evaluate the association of statin use and preoperative serum lipid parameters with oncologic outcomes following surgery for renal cell carcinoma. A total of 850 patients who underwent surgery for localized renal cell carcinoma at our institution from 2000 to 2012 were included. Use of statins, preoperative serum lipid profile, and comprehensive clinicopathologic features were retrospectively recorded. Kaplan-Meier analysis and multivariate Cox proportional hazards model were employed to compare survival outcomes. There were 342 statin users and 508 non-users. Median follow-up was 25.0 months. Statin users were older, had greater body mass index, and had worse performance status than non-users. Tumor pathologic characteristics were balanced between groups. Five-year recurrence free survival (RFS) was 77.9% for non-users compared with 87.6% for statin users (P = .004). After adjustment for clinicopathologic variables, statin use was independently associated with improved RFS (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.33-0.86, P = .011) and overall survival (HR 0.45, 95%CI 0.28-0.71, P = .001). In patients with available serum lipid parameters (n = 193), 5-year RFS was 83.8% for patients with triglycerides <250 mg/dL compared with 33.3% for those with triglycerides >250 mg/dL (P <.0001). Elevated serum triglycerides (>250 mg/dL) was independently associated with worse RFS (HR 2.69, 95%CI 1.22-5.93, P = .015) on multivariate analysis. Statin use was independently associated with improved survival, whereas elevated serum triglyceride levels correlated with worse oncologic outcomes in this cohort. These findings warrant validation in prospective studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population

PubMed Central

Qu, Yuanyuan; Gu, Chengyuan; Wang, Hongkai; Chang, Kun; Yang, Xiaoqun; Zhou, Xiaoyan; Dai, Bo; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Ye, Dingwei

2016-01-01

This study aimed to assess the utility of transcription factor E3 (TFE3) break-apart fluorescence in situ hybridization (FISH) assay in diagnosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and to compare the clinicopathological features between adult Xp11.2 RCC and non-Xp11.2 RCC. 76 pathologically suspected Xp11.2 RCCs were recruited from our institution. Both TFE3 immunohistochemistry (IHC) and TFE3 FISH assay were performed for the entire cohort. The progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. FISH analysis confirmed 30 Xp11.2 RCCs, including 28 cases with positive TFE3 immunostaining and 2 cases with negative immunostaining. The false-positive and false-negative rates were 6.7% (2/30) and 4.3% (2/46), respectively, for TFE3 IHC compared with FISH assay. Xp11.2 RCC was significantly associated with higher pathological stage and Fuhrman nuclear grade compared with non-Xp11.2 RCC (P < 0.05). The median PFS and OS for TFE3 FISH-positive group were 13.0 months (95% CI, 8.4–17.6 months) and 50.0 months (95% CI, 27.6–72.4 months), respectively, while the median PFS and OS had not been reached for TFE3 FISH-negative group. In conclusion, TFE3 break-apart FISH assay is a highly useful and standard diagnostic method for Xp11.2 RCC. Adult Xp11.2 RCC is clinically aggressive and often presents at advanced stage with poor prognosis. PMID:26880493

Diagnosis of adults Xp11.2 translocation renal cell carcinoma by immunohistochemistry and FISH assays: clinicopathological data from ethnic Chinese population.

PubMed

Qu, Yuanyuan; Gu, Chengyuan; Wang, Hongkai; Chang, Kun; Yang, Xiaoqun; Zhou, Xiaoyan; Dai, Bo; Zhu, Yao; Shi, Guohai; Zhang, Hailiang; Ye, Dingwei

2016-02-16

This study aimed to assess the utility of transcription factor E3 (TFE3) break-apart fluorescence in situ hybridization (FISH) assay in diagnosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and to compare the clinicopathological features between adult Xp11.2 RCC and non-Xp11.2 RCC. 76 pathologically suspected Xp11.2 RCCs were recruited from our institution. Both TFE3 immunohistochemistry (IHC) and TFE3 FISH assay were performed for the entire cohort. The progression-free survival (PFS) and overall survival (OS) curves were estimated using the Kaplan-Meier method. FISH analysis confirmed 30 Xp11.2 RCCs, including 28 cases with positive TFE3 immunostaining and 2 cases with negative immunostaining. The false-positive and false-negative rates were 6.7% (2/30) and 4.3% (2/46), respectively, for TFE3 IHC compared with FISH assay. Xp11.2 RCC was significantly associated with higher pathological stage and Fuhrman nuclear grade compared with non-Xp11.2 RCC (P < 0.05). The median PFS and OS for TFE3 FISH-positive group were 13.0 months (95% CI, 8.4-17.6 months) and 50.0 months (95% CI, 27.6-72.4 months), respectively, while the median PFS and OS had not been reached for TFE3 FISH-negative group. In conclusion, TFE3 break-apart FISH assay is a highly useful and standard diagnostic method for Xp11.2 RCC. Adult Xp11.2 RCC is clinically aggressive and often presents at advanced stage with poor prognosis.

Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form.

PubMed

Obari, Abdulkader; Sano, Toshiaki; Ohyama, Kenichi; Kudo, Eiji; Qian, Zhi Rong; Yoneda, Akiko; Rayhan, Nasim; Mustafizur Rahman, Muhammad; Yamada, Shozo

2008-01-01

Pituitary adenomas producing almost exclusively growth hormones (GH) have been ultrastructurally classified into two distinct types: densely granulated somatotroph (DG) adenomas and sparsely granulated (SG) adenomas. Fibrous body (FB), an intracytoplasmic globular aggregation of cytokeratin (CK) filaments, is a hallmark of SG adenomas. Under light microscope, FB could be identified by CK immunohistochemistry as a dot-pattern immunoreaction versus a perinuclear pattern for cells without FB. However, it has been noted that numerous adenomas contain mixed populations of the two patterns. To clarify clinicopathological characteristics of the adenomas with mixed populations ("intermediate type" adenomas) and to confirm clinicopathological differences between strictly defined DG-type and SG-type adenomas, we performed this study on 104 GH cell adenomas. Having segregated "intermediate-type" adenomas (26 cases), we found significant differences between typical DG-type (47 cases) and SG-type adenomas (31 cases); SG-type adenomas had younger ages (44 vs. 50), higher frequency of macroadenomas (86% vs. 58%), invasiveness (65% vs. 38%), advanced grades (3 or 4) in Knosp's classification (50% vs. 24%), and weaker immunoreaction for GH, beta-TSH, alpha-subunit, E-cadherin, and beta-catenin. Clinicopathological characteristics of "intermediate-type" adenomas were identical to those of DG-type adenomas. These findings confirm that SG-type adenoma is a distinct section of GH cell adenomas with special properties and biological behavior, and suggest that intermediate-phenotype adenomas are enrolled in DG-type adenomas. Special properties and biological behavior of SG-type adenomas may appear after the majority of tumor cells possess a fully developed fibrous body.

Clinicopathological observations in experimental peste des petit ruminants virus and Mannheimia haemolytica A:2 co-infection in goats.

PubMed

Emikpe, B O; Akpavie, S O

2012-12-18

The experiment describes for the first time the clinicopathological features of the co-infection of Peste des petit Ruminants (PPR) virus and Mannheimia haemolytica,in goats. Twenty clinically healthy goats, six months of age were used. 15 goats were infected by intratracheal inoculation of 1ml of pure cultured 106.5 TCID50 PPR virus grown in Baby hamster kidney cell lines, and a week later,1 ml of pure culture (109 CFU) of Mannheimia haemolytica (MH)A2 to study its clinico-pathological features and five goats served as controls. The clinical signs were observed and two goats were euthanized at predetermined intervals for gross examinations, bacteriological, virological and histopathological investigations on tissues collected using standard techniques. The clinical signs were severe and the order of manifestation was anorexia, pyrexia, dyspnea, oculo-nasal discharge, recumbency and death. The lesions observed were severe fibrinous bronchointerstitial pneumonia and pleurisy with thickened alveolar septa, edema and neutrophilic infiltrations of the interstitium with giant cells. There was also marked erosive stomatitis and acute enteritis. The average percentage lung consolidation for the infection was 7.01% and the right lung was more affected (p<0.05) while the overall mortality was 33.3%. MHA:2 and PPR virus were re-isolated from the lungs. The clinicopathological features observed showed that goats were susceptible to co- infection of PPR and Mannheimiosis which was severe and fatal. The data should help veterinarians and other medical experts to recognize cases of bacterial complicated viral infection and be informed of the approach to the treatment of such conditions.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study.

PubMed

Hamilton, C A; Miller, A; Casablanca, Y; Horowitz, N S; Rungruang, B; Krivak, T C; Richard, S D; Rodriguez, N; Birrer, M J; Backes, F J; Geller, M A; Quinn, M; Goodheart, M J; Mutch, D G; Kavanagh, J J; Maxwell, G L; Bookman, M A

2018-02-01

To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. Published by Elsevier Inc.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study

PubMed Central

Hamilton, C. A.; Miller, A.; Casablanca, Y.; Horowitz, N. S.; Rungruang, B.; Krivak, T. C.; Richard, S. D.; Rodriguez, N.; Birrer, M.J.; Backes, F.J.; Geller, M.A.; Quinn, M.; Goodheart, M.J.; Mutch, D.G.; Kavanagh, J.J.; Maxwell, G. L.; Bookman, M. A.

2018-01-01

Objective To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. Methods Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10 years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). Results The analysis dataset included 3,010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. Conclusions The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors. PMID:29195926

RELATIONSHIP BETWEEN THE PROANGIOGENIC ROLE OF EG-VEGF, CLINICOPATHOLOGICAL CHARACTERISTICS AND SURVIVAL IN TUMORAL OVARY.

PubMed

Lozneanu, Ludmila; Avădănei, Roxana; Cîmpean, Anca Maria; Giuşcă, Simona Eliza; Amălinei, Cornelia; Căruntu, Irina-Draga

2015-01-01

To prove the presence of EG-VEGF in tumor ovary and to analyze its involvement in the ovarian carcinogenesis, as promoter of angiogenesis, in relationship with the clinicopathological prognostic factors and survival. The study group comprises tumor tissue specimens from 50 cases of surgically treated ovarian cancer that were immunohistochemically investigated. A scoring system based on the percentage of positive cells and the intensity of staining was applied for the semiquantitative assessment of EG-VEGF, as negative or positive. Statistics involved χ2 test, and Kaplan-Meier and log-rank test. EG-VEGF was positive in 35 cases (70%) and negative in 15 cases (30%). Our data confirmed the predominance of EG-VEGF positivity in the serous subiype as compared to endometrioid and clear cell subtypes, and its absence in mucinous subtype. Moreover, we demonstrated that EG-VEGF is overexpressed mainly in high-grade ovarian carcinomas (type II) than in low-grade ones. Significant differences were registered between the EG-VEGF positive or negative expression and tumor stage and histological subtypes, respectively. Survival analysis showed no differences in patient's survival and EG-VEGF positive and negative cases. The analysis of EG-VEGF expression in ovarian tumors points out the relationship between the enhanced potential for tumor angiogenesis and the tumor aggressivity.

Acute pancreatitis in cats with hepatic lipidosis.

PubMed

Akol, K G; Washabau, R J; Saunders, H M; Hendrick, M J

1993-01-01

The purpose of this study was to characterize the incidence, clinical features, and prognosis of acute pancreatitis in cats with hepatic lipidosis. Of 13 cats histologically diagnosed with hepatic lipidosis between July 1988, and November 1989, 5(38%) were also histologically diagnosed with acute pancreatitis. In cats with hepatic lipidosis alone, the signalment, history, physical examination, and clinicopathologic findings were generally indistinguishable from those of cats with concurrent acute pancreatitis except that cats with acute pancreatitis were more likely to be cachectic and to have coagulation abnormalities. Hepatomegaly was seen on abdominal radiographs in both groups. Of the 5 cats with concurrent acute pancreatitis, abdominal ultrasonography detected 1 cat with a hypoechoic pancreas and 5 with peritoneal effusion; those abnormalities were not seen in cats without concurrent acute pancreatitis. Cats with concurrent acute pancreatitis had only a 20% recovery rate, compared with a 50% recovery rate in cats with hepatic lipidosis alone. We conclude that cats with hepatic lipidosis should be rigorously evaluated for concurrent acute pancreatitis because of 1) the rate of disease coincidence, 2) the inability of signalment, history, physical examination, and clinicopathologic findings to adequately distinguish between hepatic lipidosis and acute pancreatitis, 3) the worse prognosis associated with concurrent acute pancreatitis, and 4) the opposing nutritional strategies for hepatic lipidosis and acute pancreatitis.

Angiodrastic Chemokines in Colorectal Cancer: Clinicopathological Correlations.

PubMed

Emmanouil, George; Ayiomamitis, George; Zizi-Sermpetzoglou, Adamantia; Tzardi, Maria; Moursellas, Andrew; Voumvouraki, Argyro; Kouroumalis, Elias

2018-01-01

To study the expression of angiodrastic chemokines in colorectal tumors and correlate findings with clinicopathological parameters and survival. The proangiogenic factor VEGF, the angiogenic chemokines CXCL8 and CXCL6, and the angiostatic chemokine CXCL4 were measured by ELISA in tumor and normal tissue of 35 stage II and III patients and correlated with the histopathology markers Ki67, p53, p21, bcl2, EGFR, and MLH1 and 5-year survival. The Wilcoxon and chi-square tests were used for statistical comparisons. There was a significant increase of CXCL6 ( p = 0.005) and VEGF ( p = 0.003) in cancerous tissue compared to normal. Patients with lower levels of CXCL8 and CXCL4 lived significantly longer. Patients with loss of EGFR expression had higher levels of CXCL8 while p21 loss was associated with higher levels of CXCL6. Chemokine levels were not correlated with TNM or Dukes classification. Strong expression of p53 was accompanied by decreased survival. (1) The angiogenic factors CXCL6 and VEGF are increased in colorectal cancer tissue with no association with the clinical stage of the disease or survival. (2) However, increased levels of tissue CXCL8 and CXCL4 are associated with poor survival. (3) Strong expression of p53 is found in patients with poor survival.

Downregulation of SASH1 correlates with poor prognosis in cervical cancer.

PubMed

Xie, J; Zhang, W; Zhang, J; Lv, Q-Y; Luan, Y-F

2017-10-01

The aim of this study was to analyze the association of SASH1 expression with clinicopathological features and prognosis in patients suffering cervical cancer. The expressions of SASH1 mRNA and protein in cervical cancer tissues and matched normal cervical tissues were detected by Real-time PCR and Immunohistochemistry. Based on the above findings, the association among SASH1 expression and clinicopathological features was analyzed. Overall survival was evaluated using the Kaplan-Meier method. The variables were used in univariate and multivariate analysis by the Cox proportional hazards model. The results demonstrated that both SASH1 mRNA and proteins were downregulated in cervical cancer tissues compared with those in matched normal tissues (both p < 0.05). Also, decreased SASH1 expression in cervical cancer was found to be significantly associated with high FIGO Stage (p = 0.001), lymph nodes metastasis (p = 0.003) and differentiation (p = 0.018). Furthermore, Kaplan-Meier analysis demonstrated that low SASH1 expression level was associated with poorer overall survival (p < 0.01). Univariate and multivariate analyses indicated that status of SASH1 was an independent prognostic factor for patients with cervical cancer. These findings suggested that SASH1 can be useful as a new prognostic marker and therapeutic target in cervical cancer patients.

Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma

PubMed Central

Yang, Yu-Shang; Hu, Wei-Peng; Ni, Peng-Zhi; Wang, Wen-Ping; Yuan, Yong; Chen, Long-Qi

2017-01-01

Background Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). Methods The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients’ overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. Results The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Conclusions Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment. PMID:28118615

Effects of Chronic Lymphocytic Thyroiditis on the Clinicopathological Features of Papillary Thyroid Cancer.

PubMed

Babli, Saleha; Payne, Richard J; Mitmaker, Elliot; Rivera, Juan

2018-03-01

The effects of chronic lymphocytic thyroiditis (CLT) on the presentation and outcome of papillary thyroid carcinoma (PTC) have long been a topic of controversy. To evaluate the effect of coexistent CLT on the clinicopathological features of PTC. Retrospective study. All patients with PTC who had been followed by the 2 co-investigators (Juan Rivera and Richard J. Payne) between 2006 and 2011 were included. CLT was present in 35% (166) of the included patients and was associated with a higher proportion of patients with TNM stage I ( p = 0.027) and fewer patients with persistent disease ( p = 0.014) in comparison with the PTC-only group. Analysis of the data based on age (<45 or >45 years) revealed that in the older group, the presence of CLT was associated with fewer patients with persistent disease ( p = 0.03) and capsular invasion ( p = 0.05). However, in patients <45 years of age, the presence of CLT was associated with more capsular invasion ( p = 0.003) and extrathyroidal extension ( p = 0.004) compared with the PTC-only group. CLT in patients with PTC was associated with lower-stage disease and less disease persistence in patients >45 years of age. In patients <45 years, the presence of CLT appeared to be associated with unfavorable pathological features.

Osteopontin expression and clinicopathologic correlation of oral hyperplastic reactive lesions: An institutional 6-year retrospective study.

PubMed

Narwal, Anjali; Bala, Shashi

2017-01-01

Reactive proliferations of oral cavity comprise pyogenic granuloma (PG), fibrous hyperplasia (FH), peripheral ossifying fibroma (POF), and peripheral giant-cell granuloma (PGCG). They often pose diagnostic challenges due to their overlapping clinical and histopathological features. This study was conducted to determine the frequency and clinicopathological correlation of reactive hyperplastic lesions in the oral cavity reported in our institute and compared it with other previous studies. Further evaluation of osteopontin (OPN) expression in normal gingival tissue and different types of focal reactive lesions was also done. Data of all reactive hyperplasias were retrieved, reviewed, and analyzed for age, gender, clinical presentation, and site of location. Presence and distribution of OPN were assessed using immunohistochemistry in these reactive lesions. Two hundred and forty-eight reactive lesions were comprised of FH (38%), PG (23%), POF (13%), and PGCG (7%). FH was more common in males (55%) whereas other reactive lesions were more in females (68%-73%). The most frequently involved site was gingiva (59%), and most common clinical presentation was sessile growth on gingiva. OPN expression was minimal in normal gingiva. Few cases of FH, PG, and all cases of POF showed positivity for OPN in inflammatory cells, stromal cells, extracellular matrix, and in calcifications. Reactive hyperplastic lesions of oral cavity are mucosal responses to chronic low-grade irritation caused by plaque, calculus, and any other irritant. It is helpful to know their frequency and presentation as their early identification enables accurate patient evaluation and management.

Prevalence of Hippocampal Sclerosis in a Clinicopathologically Characterized Cohort.

PubMed

Malek-Ahmadi, Michael; Kahlon, Vickram; Adler, Charles H; Obradov, Aleksandra; Thind, Kabir; Shill, Holly A; Sue, Lucia I; Caviness, John N; Jacobson, Sandra; Sabbagh, Marwan N

2013-01-01

Hippocampal sclerosis (HS) is a neuropathological finding that frequently occurs with pathologies, such as Alzheimer's disease (AD). Prevalence estimates of HS in autopsy-confirmed dementia samples have varied between 0.4% and 24.5%. However, the prevalence of HS within other pathologic groups has not been well characterized. Utilizing a sample of 910 prospectively followed and clinicopathologically confirmed dementia cases, we determined the prevalence of HS among the sample and within specific pathologic groups. HS prevalence of the sample was compared to reported HS prevalence rates in other autopsy-confirmed dementia samples. The age range of the sample was 43 to 106 years, with a mean of 81.49±8.45. Of the 910 cases, 505 were male and 405 were female. For the entire sample, the average educational level was 14.59±2.65years. Of the 910 individuals, 47 (5.16%) cases had HS pathology present at autopsy. Among the 561 AD cases, 26 (4.43%) had HS pathology present. The frontotemporal dementia (FTD)/Pick's group had the highest percentage of cases with HS pathology (23.08%) followed by primary progressive aphasia (PPA) (16.67%) and Parkinson's disease with dementia (PDD) (5.34%). The HS prevalence rate of this study was not significantly different from all but 2 studies. The prevalence of HS pathology in this sample of autopsy-confirmed dementia cases was similar to other reported HS prevalence rates. This study is the first to report the presence of HS pathology in PDD cases.

Analysis of recently identified prostate cancer susceptibility loci in a population-based study: Associations with family history and clinical features

PubMed Central

FitzGerald, Liesel M.; Kwon, Erika M.; Koopmeiners, Joseph S.; Salinas, Claudia A.; Stanford, Janet L.; Ostrander, Elaine A.

2009-01-01

Purpose Two recent genome-wide association studies have highlighted several SNPs purported to be associated with prostate cancer risk. We investigated the significance of these SNPs in a population-based study of Caucasian men, testing the effects of each SNP in relation to family history of prostate cancer and clinicopathological features of disease. Experimental Design We genotyped 13 SNPs in 1,308 prostate cancer patients and 1,267 unaffected controls frequency matched to cases by five-year age groups. The association of each SNP with disease risk and stratified by family history of prostate cancer and clinicopathological features of disease was calculated using logistic and polytomous regression. Results These results confirm the importance of multiple previously reported SNPs in relation to prostate cancer susceptibility; 11 of the 13 SNPs were significantly associated with risk of developing prostate cancer. However, none of the SNP associations were of comparable magnitude to that associated with having a first-degree family history of the disease. Risk estimates associated with SNPs rs4242382 and rs2735839 varied by family history, while risk estimates for rs10993994 and rs5945619 varied by Gleason score. Conclusions Our results confirm that several recently identified SNPs are associated with prostate cancer risk; however the variant alleles only confer a low to moderate relative risk of disease and are generally not associated with more aggressive disease features. PMID:19366831

Prognostic and clinicopathological significance of PD-L1 in patients with renal cell carcinoma: a meta-analysis based on 1863 individuals.

PubMed

Wang, Zhun; Peng, Shuanghe; Xie, Hui; Guo, Linpei; Cai, Qiliang; Shang, Zhiqun; Jiang, Ning; Niu, Yuanjie

2018-05-01

The prognostic significance of PD-L1 in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain controversial. The primary aim of this meta-analysis was to investigate the prognostic and clinicopathological significance of the PD-L1 expression in patients with RCC. Relevant literature was identified form PubMed, Embase, Web of Science and Cochrane library, which compared the prognostic significance between PD-L1 expression and RCC. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters associated with PD-L1 were extracted from eligible studies. Heterogeneity was assessed using the I 2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. A total of 1863 patients from ten eligible studies were analyzed. The results showed that PD-L1 expression is associated with poor overall survival in clear cell RCC (ccRCC) (HR = 2.76, 95%CI: 2.25-3.38, I 2  = 14.4%, P < 0.001) and non-clear cell RCC (non-ccRCC) (HR = 2.77, 95%CI: 1.62-4.72, I 2  = 28.8%, P < 0.001). In addition, PD-L1 expression was found to be significantly associated with primary tumor stage (OR = 1.76, 95%CI: 1.39-2.23; I 2  = 56.3%), regional lymph node involvement (OR = 2.10, 95%CI: 1.48-2.98; I 2  = 14.9%), distant metastases (OR = 2.69, 95%CI: 2.05-3.54; I 2  = 0.0%), nuclear grade (OR = 1.72, 95%CI: 1.32-2.23; I 2  = 79.4%) and histologic tumor necrosis (OR = 2.25, 95%CI: 1.59-3.18; I 2  = 66.1%) in patients with RCC. The outcome stability was confirmed by sensitivity analysis. Both the Begg's funnel plot test (P = 0.276) and the Egger's (P = 0.388) verified that there was no publication bias within the included studies. This study suggests that PD-L1 expression is correlated with poor prognosis and advanced clinicopathological features in RCC patients.

Seven-year survey of classical and pleomorphic invasive lobular breast carcinomas in women from southeastern Serbia: Differences in clinicopathological and immunohistochemical features.

PubMed

Ilic, Ivan R; Djordjevic, Nebojsa P; Randjelovic, Pavle J; Stojanovic, Nikola M; Radulovic, Niko S; Ilic, Ratko S

2016-01-01

The occurrence of different variants of invasive lobular carcinoma (ILC) of the breast is variable. For example, the pleomorphic variant of ILC has an incidence of around 5%; however, the number of analyzed cases of ILC is shadowed by the number of ductal type carcinoma (IDC). Thus, we aimed to analyze the classical and pleomorphic ILCs in women from southeastern Serbia. Analyzed were 296 cases (11.91%) diagnosed with ILC, out of 2486 cases of all breast cancers (BCs), during a 7-year period (2005-2011) from southeastern Serbia. The differences in clinicopathological and immunohistochemical features (estrogen receptor/ER, progesterone receptor/ PR, HER-2, Ki-67, BRCA-1, p53 and E-cadherin) of these cases of ILCs were assessed and compared. Pleomorphic ILC occurred relatively rarely compared to other variants, however almost one fifth of the ILC cases were pleomorphic. No statistically significant correlation was found between patient age, tumor stage and the presence/absence of multifocality (MFC), multicentricity (MCC) and bilaterality (BL) on one side, and ILC variant on the other. Only the expression of two prognostic and predictive immunohistochemical markers, important for endocrine therapy, ER and PR, showed significant correlation with the ILC variant. Although higher tumor stage, incidence of multicentricity, overexpression of HER2 and higher p53 positivity were deemed to be characteristic of pleomorphic ILC, in our study that included a much larger number of cases than previous studies did, such correlations were not observed. Thus, it appears that the only two features of pleomorphic ILCs is absence of ER and PR positivity.

A population-based analysis of Head and Neck hemangiopericytoma.

PubMed

Shaigany, Kevin; Fang, Christina H; Patel, Tapan D; Park, Richard Chan; Baredes, Soly; Eloy, Jean Anderson

2016-03-01

Hemangiopericytomas (HPC) are tumors that arise from pericytes. Hemangiopericytomas of the head and neck are rare and occur both extracranially and intracranially. This study analyzes the demographic, clinicopathologic, treatment modalities, and survival characteristics of extracranial head and neck hemangiopericytomas (HN-HPC) and compares them to HPCs at other body sites (Other-HPC). The Surveillance, Epidemiology, and End Results (SEER) database (1973-2012) was queried for HN-HPC (121 cases) and Other-HPC (510 cases). Data were analyzed comparatively with respect to various demographic and clinicopathologic factors. Disease-specific survival (DSS) was analyzed using the Kaplan-Meier model. There was no significant difference in age at time of diagnosis between HN-HPC and Other-HPC. Head and neck HPC was most commonly located in the connective and soft tissue (18.4%), followed by the nasal cavity and paranasal sinuses (8.5%). Head and neck HPCs were smaller than Other-HPC (P < 0.0001) and more likely to be a lower histologic grade (P < 0.0097). The primary treatment modality for HN-HPC was surgery alone, used in 55.8% of cases. The 5-, 10-, and 20-year DSS for HN-HPC were 84.0%, 79.4%, and 69.4%, respectfully. Higher histologic grade and the presence of distant metastases were poor prognostic factors for HN-HPC. Head and neck HPCs are rare tumors. This study represents the largest series of HN-HPCs to date. Surgery alone is the primary treatment modality for HN-HPC, with a favorable prognosis. Adjuvant radiotherapy does not appear to confer a survival benefit for any body site. 4. Laryngoscope, 126:643-650, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Does Harvey-Ras gene expression lead to oral squamous cell carcinoma? A clinicopathological aspect

PubMed Central

Krishna, Akhilesh; Singh, Shraddha; Singh, Vineeta; Kumar, Vijay; Singh, Uma Shankar; Sankhwar, Satya Narayan

2018-01-01

Background: Harvey-Ras (H-Ras) is an important guanosine triphosphatase protein for the regulation of cellular growth and survival. Altered Ras signaling has been observed in different types of cancer either by gene amplification and/or mutation. The H-Ras oncogene mutations are well reported, but expression of the H-Ras gene is still unknown. Objective: This study aimed to examine both protein and messenger-RNA (mRNA) expressions of H-Ras in oral squamous cell carcinoma (OSCC) and analyzed the association with risk habits and the clinicopathological profile of cases. Methodology: A total of 65 tissue specimens of OSCC (case group) and equal number of normal tissues (control group) were included in this study. H-Ras protein and mRNA expressions were analyzed using immunohistochemical and quantitative real time-polymerase chain reaction techniques, respectively. Results: The H-Ras protein was significantly overexpressed in the oral carcinoma group compared to the normal group (P = 0.03). Most of the OSCC cases showed positive staining with moderate expression, while negative and moderate staining was high in the control group. The majority of H-Ras positive cases were found in individuals with multiple risk habits including tobacco chewing. The risk of H-Ras positivity was 1.46 times higher in smokers than non-smokers. H-Ras positivity increased in cases affected with buccal mucosa site and higher grade of carcinoma. Relative mRNA level of H-Ras was significantly elevated in oral carcinoma as compared with the control group (P ≤ 0.001). Protein and mRNA levels of H-Ras in case group was poorly correlated. Conclusion: H-Ras oncogene expression was markedly higher in oral carcinoma, and it can be a prognostic marker and target for an effective molecular therapy. PMID:29731559

Lymphocytic Esophagitis: An Emerging Clinicopathologic Disease Associated with Dysphagia.

PubMed

Pasricha, Sarina; Gupta, Amit; Reed, Craig C; Speck, Olga; Woosley, John T; Dellon, Evan S

2016-10-01

Lymphocytic esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. The aim of this study was to characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000, and June 1, 2012. Archived pathology slides were re-reviewed, and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Twenty-seven adults were diagnosed with LyE, and the majority were female (63 %). The most common symptom was dysphagia (70 %). Fifty-two percentage had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37 %), erosive esophagitis (33 %), rings (26 %), and hiatal hernia (26 %); 33 % of patients required dilation. After histology re-review, 78 % of LyE patients were found to have more than 20 lymphs/hpf. In comparison with the normal, reflux and EoE controls, patients with LyE tended to be nonwhite (p < 0.01), were more commonly tobacco users (p = 0.02) and less likely to have seasonal allergies (p = 0.02). LyE commonly presents with dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE, whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy.

FBXW7 expression affects the response to chemoradiotherapy and overall survival among patients with oral squamous cell carcinoma: A single-center retrospective study.

PubMed

Arita, Hidetaka; Nagata, Masashi; Yoshida, Ryoji; Matsuoka, Yuichiro; Hirosue, Akiyuki; Kawahara, Kenta; Sakata, Junki; Nakashima, Hikaru; Kojima, Taku; Toya, Ryo; Murakami, Ryuji; Hiraki, Akimitsu; Shinohara, Masanori; Nakayama, Hideki

2017-10-01

FBXW7 (F-box and WD repeat domain containing-7) is a tumor suppressor protein that regulates the degradation of various oncoproteins in several malignancies. However, limited information is available regarding FBXW7 expression in oral squamous cell carcinoma. Therefore, this study aimed to determine the clinical significance of FBXW7 expression in oral squamous cell carcinoma. The FBXW7 expression patterns in oral squamous cell carcinoma and adjacent normal tissues from 15 patients who underwent radical resection were evaluated using quantitative real-time polymerase chain reaction and immunohistochemical staining. In addition, immunohistochemistry was performed using paraffin-embedded sections from biopsy specimens obtained from 110 patients with oral squamous cell carcinoma who underwent surgery after 5 fluorouracil-based chemoradiotherapy. The associations of FBXW7 expression with various clinicopathological features and prognosis were evaluated in these patients. As a results, in the 15 matched samples, the FBXW7 expression was significantly decreased in the oral squamous cell carcinoma tissues compared to that in the adjacent normal tissues. In the clinicopathological analysis, compared to high protein expression, low FBXW7 expression was found to significantly associate with a poor histological response to preoperative chemoradiotherapy. Kaplan-Meier curve analysis revealed that low FBXW7 expression was significantly associated with a poor prognosis, and FBXW7 expression was found to be an independent predictor of overall survival in the multivariate analysis. Our results suggest that FBXW7 may function as a tumor suppressor protein in oral squamous cell carcinoma. In addition, FBXW7 could be a potential biomarker for predicting not only the clinical response to chemoradiotherapy but also overall survival in patients with oral squamous cell carcinoma.

The relationship between genetic profiling, clinicopathological factors and survival in patients undergoing surgery for node-negative colorectal cancer: 10-year follow-up.

PubMed

Powell, Arfon G M T; Ferguson, Jenny; Al-Mulla, Fahd; Orange, Clare; McMillan, Donald C; Horgan, Paul G; Edwards, Joanne; Going, James J

2013-12-01

The introduction of the bowel cancer screening programme has resulted in increasing numbers of patients being diagnosed with node-negative disease. Unfortunately, approximately 30 % will develop recurrence following surgery. Given the toxicity associated with adjuvant chemotherapy, it is important to identify high-risk patients who may benefit from adjuvant therapy. This study aims to identify which clinicopathological factors and genetic profiling markers predict outcome in node-negative disease. Forty-nine microsatellite stable (MSS) patients undergoing curative resection between 1991 and 1993 were included. Local immune response was assessed by Klintrup criteria and vascular invasion status assessed through Miller's elastin staining. Comparative genomic hybridisation (CGH) on a range of loci provided data on allelic imbalance. Analysis of survival included clinicopathological and CGH data in a multivariate (Cox) model. On binary logistical regression analysis, 4p deletion was independently associated with low Klintrup score (HR 0.16; 95 % CI (0.03-0.96); P = 0.045), venous invasion (HR 4.19; 95 % CI (1.08-16.29); P = 0.039) and higher Dukes' stage (HR 6.43; 95 % CI (1.22-33.97); P = 0.028). Minimum follow-up was 109 months and there were 24 cancer deaths. On multivariate analysis, high Klintrup score (HR 0.33; 95 % CI (0.12-0.93); P = 0.036), 4p- (HR 4.01; 95 % CI (1.58-10.21); P = 0.004) and 5q- (HR 3.81; 95 % CI (1.54-9.47); P = 0.004) were significantly associated with survival. 4p-, 5q- and low Klintrup score were independently associated with poor cancer-specific survival in node-negative MSS colorectal cancer. Confirmatory work in a larger cohort is needed to determine whether these markers may be used to identify patients who may benefit from adjuvant chemotherapy.

Oral squamous cell carcinoma: clinicopathological features from 346 cases from a single Oral Pathology service during an 8-year period

PubMed Central

PIRES, Fábio Ramôa; RAMOS, Amanda Barreto; de OLIVEIRA, Jade Bittencourt Coutinho; TAVARES, Amanda Serra; da LUZ, Priscilla Silva Ribeiro; dos SANTOS, Teresa Cristina Ribeiro Bartholomeu

2013-01-01

Epidemiological data from oral squamous cell carcinoma (OSCC) is mostly derived from North American, European and East Asian populations. Objective The aim of this study was to report the demographic and clinicopathological features from OSCC diagnosed in an Oral Pathology service in southeastern Brazil in an 8-year period. Material and Methods All OSCC diagnosed from 2005 to 2012 were reviewed, including histological analysis of all hematoxylin and eosin stained slides and review of all demographic and clinical information from the laboratory records. Results A total of 346 OSCC was retrieved and males represented 67% of the sample. Mean age of the patients was 62.3 years-old and females were affected a decade older than males (p<0.001). Mean time of complaint with the tumors was 10 months and site distribution showed that the border of the tongue (37%), alveolar mucosa/gingiva (20%) and floor of mouth/ventral tongue (19%) were the most common affected sites. Mean size of the tumors was 3.4 cm, with no differences for males and females (p=0.091) and males reported both tobacco and alcohol consumption more frequently than females. Histological grade of the tumors revealed that 27%, 40% and 21% of the tumors were, respectively, classified as well-, moderately- and poorly-differentiated OSCC, 26 cases (7.5%) were microinvasive OSCC and 17 cases were OSCC variants. OSCC in males mostly affected the border of tongue, floor of mouth/ventral tongue and alveolar mucosa/gingival, while they were more frequent on the border of tongue, alveolar mucosa/gingival and buccal mucosa/buccal sulcus in females (p=0.004). Conclusions The present data reflect the epidemiological characteristics of OSCC diagnosed in a public Oral Pathology laboratory in southeastern Brazil and have highlighted several differences in clinicopathological features when comparing male and female OSCC-affected patients. PMID:24212993

Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study

PubMed Central

McMeekin, D. Scott; Tritchler, David L.; Cohn, David E.; Mutch, David G.; Lankes, Heather A.; Geller, Melissa A.; Powell, Matthew A.; Backes, Floor J.; Landrum, Lisa M.; Zaino, Richard; Broaddus, Russell D.; Ramirez, Nilsa; Gao, Feng; Ali, Shamshad; Darcy, Kathleen M.; Pearl, Michael L.; DiSilvestro, Paul A.; Lele, Shashikant B.

2016-01-01

Purpose The clinicopathologic significance of mismatch repair (MMR) defects in endometrioid endometrial cancer (EEC) has not been definitively established. We undertook tumor typing to classify MMR defects to determine if MMR status is prognostic or predictive. Methods Primary EECs from NRG/GOG0210 patients were assessed for microsatellite instability (MSI), MLH1 methylation, and MMR protein expression. Each tumor was assigned to one of four MMR classes: normal, epigenetic defect, probable mutation (MMR defect not attributable to MLH1 methylation), or MSI-low. The relationships between MMR classes and clinicopathologic variables were assessed using contingency table tests and Cox proportional hazard models. Results A total of 1,024 tumors were assigned to MMR classes. Epigenetic and probable mutations in MMR were significantly associated with higher grade and more frequent lymphovascular space invasion. Epigenetic defects were more common in patients with higher International Federation of Gynecology and Obstetrics stage. Overall, there were no differences in outcomes. Progression-free survival was, however, worse for women whose tumors had epigenetic MMR defects compared with the MMR normal group (hazard ratio, 1.37; P < .05; 95% CI, 1.00 to 1.86). An exploratory analysis of interaction between MMR status and adjuvant therapy showed a trend toward improved progression-free survival for probable MMR mutation cases. Conclusion MMR defects in EECs are associated with a number of well-established poor prognostic indicators. Women with tumors that had MMR defects were likely to have higher-grade cancers and more frequent lymphovascular space invasion. Surprisingly, outcomes in these patients were similar to patients with MMR normal tumors, suggesting that MMR defects may counteract the effects of negative prognostic factors. Altered immune surveillance of MMR-deficient tumors, and other host/tumor interactions, is likely to determine outcomes for patients with MMR-deficient tumors. PMID:27325856

Clinicopathologic Significance of Mismatch Repair Defects in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study.

PubMed

McMeekin, D Scott; Tritchler, David L; Cohn, David E; Mutch, David G; Lankes, Heather A; Geller, Melissa A; Powell, Matthew A; Backes, Floor J; Landrum, Lisa M; Zaino, Richard; Broaddus, Russell D; Ramirez, Nilsa; Gao, Feng; Ali, Shamshad; Darcy, Kathleen M; Pearl, Michael L; DiSilvestro, Paul A; Lele, Shashikant B; Goodfellow, Paul J

2016-09-01

The clinicopathologic significance of mismatch repair (MMR) defects in endometrioid endometrial cancer (EEC) has not been definitively established. We undertook tumor typing to classify MMR defects to determine if MMR status is prognostic or predictive. Primary EECs from NRG/GOG0210 patients were assessed for microsatellite instability (MSI), MLH1 methylation, and MMR protein expression. Each tumor was assigned to one of four MMR classes: normal, epigenetic defect, probable mutation (MMR defect not attributable to MLH1 methylation), or MSI-low. The relationships between MMR classes and clinicopathologic variables were assessed using contingency table tests and Cox proportional hazard models. A total of 1,024 tumors were assigned to MMR classes. Epigenetic and probable mutations in MMR were significantly associated with higher grade and more frequent lymphovascular space invasion. Epigenetic defects were more common in patients with higher International Federation of Gynecology and Obstetrics stage. Overall, there were no differences in outcomes. Progression-free survival was, however, worse for women whose tumors had epigenetic MMR defects compared with the MMR normal group (hazard ratio, 1.37; P < .05; 95% CI, 1.00 to 1.86). An exploratory analysis of interaction between MMR status and adjuvant therapy showed a trend toward improved progression-free survival for probable MMR mutation cases. MMR defects in EECs are associated with a number of well-established poor prognostic indicators. Women with tumors that had MMR defects were likely to have higher-grade cancers and more frequent lymphovascular space invasion. Surprisingly, outcomes in these patients were similar to patients with MMR normal tumors, suggesting that MMR defects may counteract the effects of negative prognostic factors. Altered immune surveillance of MMR-deficient tumors, and other host/tumor interactions, is likely to determine outcomes for patients with MMR-deficient tumors. © 2016 by American Society of Clinical Oncology.

Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women

PubMed Central

Patil, Vinayak W; Singhai, Rajeev; Patil, Amit V; Gurav, Prakash D

2011-01-01

The aim of our study was to analyze triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PgR), and the human epidermal growth factor receptor 2 (HER-2/neu) and which represents a subset of breast cancer with different biologic behavior. We investigated the clinicopathological characteristics and prognostic indicators of lymph node-negative TN breast cancer. Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Grant Medical College and Sir JJ Group of Hospitals, Mumbai, India, from May 2007 to October 2010. Clinicopathological variables and clinical outcomes were evaluated. Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (<35 years, P = 0.003) and a higher histopathologic and nuclear grade (P < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for Bcl-2 expression (P < 0.001), positive for the epidermal growth factor receptor (P = 0.003), and a high level of p53 (P < 0.001) and Ki-67 expression (P < 0.00). The relapse rates during the follow-up period (median 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (P = 0.004). Relapse-free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer: 3.5-year RFS rate 85.5% versus 94.2%, respectively; P = 0.001. On multivariate analysis, young age, close resection margin, and triple negativity were independent predictors of shorter RFS. TN breast cancer had a higher relapse rate and more aggressive clinicopathological characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into risk factor analysis for node-negative breast cancer. PMID:24367172

Is the clinicopathological pattern of colorectal carcinoma similar in the state and private healthcare systems of South Africa? Analysis of a Durban colorectal cancer database.

PubMed

Ntombela, Xolani H; Zulu, Babongile Mw; Masenya, Molikane; Sartorius, Ben; Madiba, Thandinkosi E

2017-10-01

Previous state hospital-based local studies suggest varying population-based clinicopathological patterns of colorectal cancer (CRC). Patients diagnosed with CRC in the state and private sector hospitals in Durban, South Africa over a 12-month period (January-December 2009) form the basis of our study. Of 491 patients (172 state and 319 private sector patients), 258 were men. State patients were younger than private patients. Anatomical site distribution was similar in both groups with minor variations. Stage IV disease was more common in state patients. State patients were younger, presented with advanced disease and had a lower resection rate. Black patients were the youngest, presented with advanced disease and had the lowest resection rate.

Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.

PubMed

Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang

2013-08-01

To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.

Childhood nodal marginal zone lymphoma with unusual clinicopathologic and cytogenetic features for the pediatric variant: a case report.

PubMed

Aqil, Barina; Merritt, Brian Y; Elghetany, M Tarek; Kamdar, Kala Y; Lu, Xinyan Y; Curry, Choladda V

2015-01-01

Nodal marginal zone lymphoma (NMZL) is a B-cell lymphoma that shares morphologic and immunophenotypic features with extranodal and splenic marginal zone lymphomas but lacks extranodal or splenic involvement at presentation. NMZL occurs mostly in adults with no sex predilection, at advanced stage (III or IV), with frequent relapses and a high incidence of tumoral genetic abnormalities including trisomies 3 and 18 and gain of 7q. Pediatric NMZL, however, is a rare but distinct variant of NMZL with characteristic features including male predominance, asymptomatic and localized (stage I) disease, low relapse rates with excellent outcomes, and a lower incidence of essentially similar genetic aberrations compared to adult NMZL. Here we describe a unique case of childhood NMZL with unusual clinicopathologic features for the pediatric variant including generalized lymphadenopathy, high-stage disease with persistence after therapy, unusual immunophenotype (CD5, CD23, and BCL6 positive), and unique chromosomal abnormalities including monosomy 20 and add(10)(p11.2).

[Association of serum decoy receptor 3 protein level with the clinicopathologic features of bladder transitional cell carcinoma].

PubMed

Wang, Dong; Wang, Jian; Chen, Guojun

2013-12-01

To investigate the association of serum levels of decoy receptor 3(DcR3) protein and the clinicopathologic features of bladder transitional cell carcinoma. Enzyme-linked immunosorbent assay was used to examine the serum levels of DcR3 in patients with bladder transitional cell carcinoma for analysis of its association with the patients' age, gender, clinical stages and pathological classification. The patients with bladder transitional cell carcinoma showed a significantly elevated serum level of DcR3 (183.43 ∓78.45 pg/m1) compared with the normal level (116.65∓97.43 pg/m1, P<0.05). The serum level of DcR3 in the patients showed close correlations with the TNM stage and pathological classification of the tumor (P<0.05) but not with the patients' age or gender (P>0.05). In patients with bladder transitional cell carcinoma, a high serum level of DcR3 suggests a higher malignancy of the tumor.

Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance

PubMed Central

Vincent-Chong, Vui King; Salahshourifar, Iman; Woo, Kar Mun; Anwar, Arif; Razali, Rozaimi; Gudimella, Ranganath; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Kallarakkal, Thomas George; Ramanathan, Anand; Wan Mustafa, Wan Mahadzir; Abraham, Mannil Thomas; Tay, Keng Kiong; Zain, Rosnah Binti

2017-01-01

Background Cancers of the oral cavity are primarily oral squamous cell carcinomas (OSCCs). Many of the OSCCs present at late stages with an exceptionally poor prognosis. A probable limitation in management of patients with OSCC lies in the insufficient knowledge pertaining to the linkage between copy number alterations in OSCC and oral tumourigenesis thereby resulting in an inability to deliver targeted therapy. Objectives The current study aimed to identify copy number alterations (CNAs) in OSCC using array comparative genomic hybridization (array CGH) and to correlate the CNAs with clinico-pathologic parameters and clinical outcomes. Materials and methods Using array CGH, genome-wide profiling was performed on 75 OSCCs. Selected genes that were harboured in the frequently amplified and deleted regions were validated using quantitative polymerase chain reaction (qPCR). Thereafter, pathway and network functional analysis were carried out using Ingenuity Pathway Analysis (IPA) software. Results Multiple chromosomal regions including 3q, 5p, 7p, 8q, 9p, 10p, 11q were frequently amplified, while 3p and 8p chromosomal regions were frequently deleted. These findings were in confirmation with our previous study using ultra-dense array CGH. In addition, amplification of 8q, 11q, 7p and 9p and deletion of 8p chromosomal regions showed a significant correlation with clinico-pathologic parameters such as the size of the tumour, metastatic lymph nodes and pathological staging. Co-amplification of 7p, 8q, 9p and 11q regions that harbored amplified genes namely CCND1, EGFR, TPM2 and LRP12 respectively, when combined, continues to be an independent prognostic factor in OSCC. Conclusion Amplification of 3q, 5p, 7p, 8q, 9p, 10p, 11q and deletion of 3p and 8p chromosomal regions were recurrent among OSCC patients. Co-alteration of 7p, 8q, 9p and 11q was found to be associated with clinico-pathologic parameters and poor survival. These regions contain genes that play critical roles in tumourigenesis pathways. PMID:28384287

Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD

PubMed Central

Kouri, Naomi; Oshima, Kenichi; Takahashi, Makio; Murray, Melissa E.; Ahmed, Zeshan; Parisi, Joseph E.; Yen, Shu-Hui C.; Dickson, Dennis W.

2013-01-01

CBD is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus was comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. Additionally, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology. PMID:23371366

Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD.

PubMed

Kouri, Naomi; Oshima, Kenichi; Takahashi, Makio; Murray, Melissa E; Ahmed, Zeshan; Parisi, Joseph E; Yen, Shu-Hui C; Dickson, Dennis W

2013-05-01

Corticobasal degeneration (CBD) is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon, and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus were comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. In addition, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology.

Clinicopathological characteristics of head and neck Merkel cell carcinomas.

PubMed

Knopf, Andreas; Bas, Murat; Hofauer, Benedikt; Mansour, Naglaa; Stark, Thomas

2017-01-01

There are still controversies about the therapeutic strategies and subsequent outcome in head and neck Merkel cell carcinoma. Clinicopathological data of 23 Merkel cell carcinomas, 93 cutaneous head and neck squamous cell carcinomas (HNSCCs), 126 malignant melanomas, and 91 primary parotid gland carcinomas were comprehensively analyzed. Merkel cell carcinomas were cytokeratin 20 (CK20)/neuron-specific enolase (NSE)/chromogranin A (CgA)/synaptophysin (Syn)/thyroid transcription factor-1 (TTF-1)/MIB1 immunostained. All Merkel cell carcinomas underwent wide local excision. Parotidectomy/neck dissection was performed in 40%/33% cutaneous Merkel cell carcinoma and 100%/100% in parotid gland Merkel cell carcinoma. Five-year recurrence-free interval (RFI)/overall survival (OS) was significantly higher in malignant melanoma (81/80%) than in cutaneous Merkel cell carcinoma/HNSCC. Interestingly, 5-year RFI/OS was significantly higher in Merkel cell carcinoma (61%/79%) than in HNSCC (33%/65%; p < .0001) despite comparable TNM classifications and treatment regimens. There were neither differences of RFI/OS between parotid gland Merkel cell carcinoma and parotid gland carcinomas, nor in the immunohistochemical profile. Five-year RFI/OS was significantly better in cutaneous Merkel cell carcinoma when compared with TNM classification matched HNSCC. Five-year RFI/OS was comparable in parotid gland Merkel cell carcinoma and other primary parotid gland malignancies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 92-97, 2017. © 2016 Wiley Periodicals, Inc.

Pancreatic necrosis in New World camelids: 11 cases (1990-1998).

PubMed

Pearson, E G; Snyder, S P

2000-07-15

To determine clinical, clinicopathologic, and postmortem abnormalities in New World camelids with pancreatic necrosis. Retrospective study. 10 llamas and 1 alpaca. Medical records of animals in which a diagnosis of pancreatic necrosis had been made on the basis of histologic examination of necropsy specimens or on the basis of clinical signs and results of clinicopathologic testing were reviewed. The initial owner complaint varied, and various other conditions were diagnosed. Clinical and clinicopathologic abnormalities were vague. Amylase activity was higher in abdominal fluid than in serum in 5 of 7 animals, and lipase activity was higher in abdominal fluid than in serum in all 7. Four animals survived, and 7 died or were euthanatized. Only 1 of the animals that died had marked inflammation of the pancreatic parenchyma. All 7 had necrosis and saponification of fat in and surrounding the pancreas. Results suggest that pancreatic necrosis may develop in New World camelids, but clinical signs are vague, and the condition may easily be confused with other diseases. The only laboratory test that appeared to be helpful in the antemortem diagnosis of pancreatic necrosis was comparison of amylase and lipase activities in abdominal fluid and serum.

Metastatic ovarian tumors: a clinicopathologic study of 150 cases.

PubMed

Alvarado-Cabrero, Isabel; Rodríguez-Gómez, Adriana; Castelan-Pedraza, Jorge; Valencia-Cedillo, Raquel

2013-10-01

To determine the frequency of metastatic ovarian tumors and to identify their clinicopathologic features. A total of 150 patients with pathologically confirmed metastatic ovarian carcinoma who were treated between 1995 and 2011 at the Mexican Oncology Hospital were identified by retrospective review. Clinicopathologic data were analyzed. Metastatic ovarian carcinoma accounted for 15.7% of all ovarian malignancies. The primary sites of nongynecologic tumors were the colon (30%), stomach (16%), appendix (13%), breast (13%), pancreas (12%), biliary tract (15%), and liver (4%). Gynecologic primary sites were the uterine cervix (4%) and the uterine body (23%). Primary malignancies were detected first in 66 patients (44%) and simultaneously with ovarian metastasis in 53 patients (35.3%). An ovarian mass was the first manifestation of disease in 20.6% of the cases. The patients ranged in age from 26 to 72 years (mean, 51). Krukenberg tumors were found in 35 patients (23%). The cut surfaces of the ovaries were solid in 68 patients, solid-cystic in 38, and multicystic in 44. Metastatic ovarian carcinomas are an important group of ovarian neoplasms, constituting 15.7% of all ovarian malignancies. Most of them arise from the gastrointestinal tract.

Telomere Length in Leukocyte DNA in Gastric Cancer Patients and its Association with Clinicopathological Features and Prognosis.

PubMed

Tahara, Tomomitsu; Tahara, Sayumi; Horiguchi, Noriyuki; Kawamura, Tomohiko; Okubo, Masaaki; Ishizuka, Takamitsu; Yamada, Hyuga; Yoshida, Dai; Ohmori, Takafumi; Maeda, Kohei; Komura, Naruomi; Ikuno, Hirokazu; Jodai, Yasutaka; Kamano, Toshiaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Tuskamoto, Tetsuya; Urano, Makoto; Shibata, Tomoyuki; Kuroda, Makoto; Ohmiya, Naoki

2017-04-01

Telomere shortening in leukocytes has been thought to be associated with reduced immune response capacity and increased chromosome instability. Several studies indicate that telomere length in the peripheral blood leukocyte DNA can predict clinical outcome of several cancers. We evaluated the potential association between telomere shortening in the leukocyte DNA and clinicopathological features and prognosis of gastric cancer (GC) in Japanese patients. Telomere length in leukocyte DNA was measured using quantitative real-time polymerase chain reaction (PCR) in 207 GC patients. The association between telomere length and clinicopathological features and prognosis was evaluated. These short-telomere group was significantly associated with advanced stage (p=0.015), worse overall survival (OS) and progression-free survival (PFS) (p=0.046 and 0.026, respectively). The same group was also weakly associated with overall and peritoneal recurrences (p=0.052 and 0.059, respectively). Telomere shortening in leukocyte DNA is associated with advanced stage and poor prognosis of GC, which may reflect their reduced immune response capacity or increased chromosome instability. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Non-endometrioid and high-grade endometrioid endometrial cancers show DNA fragmentation factor 40 (DFF40) and B-cell lymphoma 2 protein (BCL2) underexpression, which predicts disease-free and overall survival, but not DNA fragmentation factor 45 (DFF45) underexpression.

PubMed

Banas, Tomasz; Pitynski, Kazimierz; Okon, Krzysztof; Winiarska, Aleksandra

2018-04-13

The expression of DNA fragmentation factor 45 (DFF45) and B-cell lymphoma 2 (BCL2) in glands of the normal human endometrium is related to phases of the menstrual cycle and decreases after menopause, whereas the expression of DNA fragmentation factor 40 (DFF40) is stable. Moreover, DF45, BCL2 and DFF40 underexpression has been reported in numerous malignancies, including uterine leiomyosarcomas. In this study, we aimed to investigate DFF45, BCL2 and DFF40 expression in endometrioid and non-endometrioid types of endometrial cancers (ECs). We also evaluated the correlations between DFF45, BCL2 and DFF40 expression levels and clinicopathological parameters and determined the value of these three proteins as prognostic markers of disease-free survival (DFS) and overall survival (OS). Immunohistochemistry was performed to evaluate DFF45, BCL2 and DFF40 expression in 342 cases of ECs. Student's t-test, the Mann-Whitney U-test, and the chi-squared test were used for the statistical analyses as appropriate. The Cox-Mantel test, Cox's proportional hazard model, and relative risk analyses were used to evaluate associations between DFF40, DFF45, and BCL2 expression and clinicopathological characteristics. DFF40 and BCL2, but not DFF45, were significantly underexpressed in non-endometrioid and high-grade endometrioid ECs compared with low- and moderate-grade endometrioid ECs. Women with DFF40- and BCL2-negative tumors had higher risks of disease recurrence, lymph node involvement, lympho-vascular space infiltration, and deep myometrial invasion compared with women with DFF40- and BCL2-positive tumors. Additionally, women with DFF40- and BCL2-negative tumors had significantly lower OS and DFS than women with DFF40- and BCL2-positive tumors. A multivariable analysis of the model, including the clinicopathological characteristics and immunohistochemical results, showed that negative BCL2 expression, lymph node involvement, and high-stage and high-grade disease were independent predictors of OS, whereas negative BCL2 expression, lymph node involvement, and high-stage disease were independent predictors of DFS. Compared with low- and moderate-grade endometrioid ECs, non-endometrioid and high-grade endometrioid ECs showed significant DFF40 and BCL2 underexpression. The absence of DFF40 and BCL2 expression negatively affects DFS and OS. Further prospective studies are warranted to assess the potential utility of DFF40 and BCL2 as targets in the diagnosis or treatment of ECs.

Colorectal cancer in patients seen at the teaching hospitals of Guadeloupe and Martinique: discrepancies, similarities in clinicopathological features, and p53 status

PubMed Central

2014-01-01

Background In Guadeloupe and Martinique, two French Overseas Departments, colorectal cancer (CRC) has become an essential public health issue. However, little is known about CRC characteristics and the p53 status in these populations, particularly in Guadeloupe, whereas certification of a cancer registry has been recently validated. Methods This was a descriptive retrospective study of 201 patients who, between 1995 and 2000, underwent surgery for CRC in the Guadeloupe Teaching Hospital (GlpeTH; 83 patients) and in the Martinique Teaching Hospital (MqueTH; 118 patients). The clinicopathological features and the p53 expression, evaluated with immunohistochemistry, were compared at the time of diagnosis. A relationship between these parameters and the p53 expression was also studied. Data were analysed, using the SPSS computer software version 17.0. Results No statistical difference was found between the two groups of patients regarding age (p = 0.60), percentage of young patients (≤50 years; p = 0.94)), sex (p = 0.47), histological type (p = 0.073) and tumour sites (p = 0.65), although the GlpeTH patients were diagnosed with more distal colon cancers (54.2%) than the Mque TH patients (47.4%). By contrast, a significant difference was found regarding the tumour grade (p < 0.0001), the pTNM stage (p = 0.045) and the pT stage (p < 0.0001). Regarding p53 expression, solely for the MqueTH patients, nuclear expression was associated with pTNM, the percentage of p53 negative tumours increasing with the progression of the pTNM stages (p = 0.029). Conclusions For the first time, this study reveals discrepancies in clinicopathological features and in the p53 status between the two groups of patients. The GlpeTH patients were diagnosed with more moderated CRCs but with few CRCs at pTNM IV stage. By contrast, the MqueTH patients were diagnosed with more differentiated tumours, but with many more CRCs at pTNM IV stage. This paradox may be due to differences in tumour location (distal vs proximal), multiplicity of the genetic profiles of patients, or patients getting treatment elsewhere. Although our study is limited due to its small size, it emphasizes the originality of our results. PMID:24679126

Rectal Carcinoma: Demographics and Clinicopathological Features from Pakistani Population Perspective.

PubMed

Pirzada, Muhammad T; Ahmed, Monis J; Muzzafar, Anam; Nasir, Irfan Ul Islam; Shah, Muhammad F; Khattak, Shahid; Syed, Aamir A

2017-06-20

Colorectal carcinoma is ranked as the second most common cancer diagnosis in females and third in males. It is the third leading cause of cancer-related deaths worldwide. Disease burden has been attributed to a myriad of factors comprising genetic, environmental, and dietary factors. Rectal cancer has been shown to demonstrate variance according to the geographical location. A retrospective review of 477 rectal cancer patients treated at Shaukat Khanum Memorial Cancer Hospital & Research Centre from 2006 to 2014 was performed. Demographic and clinicopathological features were compared between the two age groups (≤40 or >40 years). These included sex, ethnicity, family history of cancer, the location of tumor, clinical staging, histopathological type, and response to chemoradiation. Chi-square was used to compare the frequencies between the two age groups. p-value < 0.05 was taken as significant. Mean age of the study group was 44.62 ± 16.11 years. 43.8% were ≤40 years of age, and 70.2% were male. 50.3% patients belong to Punjab province, 287 (60.2%) had lower rectal cancer, family history of cancer was present in 82 (17.2%) patients. 432 (90.5%) patients had T1/T2 disease and 296 (62.1%) had N2 disease. Metastatic disease at presentation was observed in 37 (7.8%). Progressive disease was found in 90 (18%) patients. High frequency of young onset rectal cancers and the lack of family history emphasize the need of indigenous strategies and national awareness of this disease for an early identification of these patients.

Comparison of clinicopathological findings among patients whose mammography results were classified as category 4 subgroups of the BI-RADS.

PubMed

Leblebici, Ihsan Metin; Bozkurt, Suleyman; Eren, Turgut Tunc; Ozemir, Ibrahim Ali; Sagiroglu, Julide; Alimoglu, Orhan

2014-01-01

Our aim is to compare mammographic, demographic and clinicopathological characteristics of patients whose mammographies were classified as subgroups of BI-RADS 4 category (Breast Imaging - Reporting and Data System). In total, 103 patients with mammography (Senographe 600t Senix HF; General Electric, Moulineaux, France) results classified as BI-RADS 4 were included in the study. Demographic data (age, menopause, and family history) were recorded. All data were compared among BI-RADS 4 subgroups. In all, 68.9% (71/103), 7.8% (8/103) and 23.3% (24/103) the patients were in groups BI-RADS 4A, 4B and 4C, respectively. The incidence of malignancy was higher in Groups 4B and 4C than in Group 4A (p<0.05), but similar in Groups 4B and 4C (p>0.05). Mean age was lower in Group 4B than in Groups 4A and 4C (p<0.05). A positive family history was more common in Group 4A than in Group 4B (p=0.025). The frequency of menopausal patients was greater in Groups 4A and 4C than in Group 4B (p=0.021, and 0.003, respectively). The rate of malignancy was higher in Groups 4B, and 4C than in Group 4A. A positive family history was more common in Group 4A than in Group 4C. Groups 4A, and 4C patients tended to be older and were more likely to be menopausal than Group 4B patients.

Progressive aphasia secondary to Alzheimer disease pathology: A clinicopathologic and MRI study

PubMed Central

Josephs, Keith A.; Whitwell, Jennifer L.; Duffy, Joseph R.; Vanvoorst, Wendy A.; Strand, Edyth A.; Hu, William T.; Boeve, Bradley F.; Graff-Radford, Neill R.; Parisi, Joseph E.; Knopman, David S.; Dickson, Dennis W.; Jack, Clifford R.; Petersen, Ronald C.

2009-01-01

Background The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive-inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD). Objective To compare clinicopathological and MRI features of subjects with progressive aphasia and AD pathology, to subjects with aphasia and FTLD-U pathology, and subjects with typical AD. Methods We identified 5 subjects with aphasia and AD pathology and 5 with aphasia and FTLD-U pathology with an MRI from a total of 216 aphasia subjects. Ten subjects with typical AD clinical features and AD pathology were also identified. All subjects with AD pathology underwent pathological re-analysis with TDP-43 immunohistochemistry. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aphasia cases with AD pathology, aphasia cases with FTLD-U, and typical AD cases with AD pathology, compared to a normal control group. Results All aphasic subjects had fluent speech output. However, those with AD pathology had better processing speed than those with FTLD-U pathology. Immunohistochemistry with TDP-43 antibodies was negative. VBM revealed grey matter atrophy predominantly in the temporoparietal cortices with notable sparing of the hippocampus in the aphasia with AD subjects. In comparison, the aphasic subjects with FTLD-U showed sparing of the parietal lobe. Typical AD subjects showed temporoparietal and hippocampal atrophy. Conclusions A temporoparietal pattern of atrophy on MRI in patients with progressive fluent aphasia and relatively preserved processing speed is suggestive of underlying AD pathology rather than FTLD-U. PMID:18166704

Metabolic and respiratory derangements associated with death in cold-stunned Kemp's ridley turtles (Lepidochelys kempii): 32 cases (2005-2009).

PubMed

Keller, Krista A; Innis, Charles J; Tlusty, Michael F; Kennedy, Adam E; Bean, Sarah B; Cavin, Julie M; Merigo, Constance

2012-02-01

To assess selected clinicopathologic variables at hospital admission (day 1) for cold-stunned Kemp's ridley turtles (Lepidochelys kempii) that died during the first 3 days after admission (nonsurvivors) and turtles that survived (survivors) and to determine the percentage change of each variable from day 1 to day of death (nonsurvivors) or to day 2 or 3 of hospitalization (survivors). Retrospective case-control study. Animals-64 stranded, cold-stunned Kemp's ridley turtles hospitalized from October 2005 through December 2009. Blood gas, pH, Hct, and selected biochemical values in blood samples determined on day 1 and day of death (nonsurvivors; n = 32) or day 2 or 3 of hospitalization (survivors; 32) were obtained from medical records. For each variable, initial values and percentage changes (from initial values to values at the day of death or day 2 or 3 of hospitalization) were compared between survivors and nonsurvivors. Compared with blood analysis findings for survivors, nonsurvivors initially had significantly higher potassium concentration and Pco(2) and significantly lower Po(2), pH, and bicarbonate concentration than did survivors. For the first 2 or 3 days of hospitalization, percentage changes in potassium, lactate, and ionized calcium concentrations were significantly higher and percentage changes in pH and plasma glucose and bicarbonate concentrations were significantly lower in nonsurvivors. At hospital admission, cold-stunned Kemp's ridley turtles were affected by metabolic and respiratory derangements; severe derangements were associated with death. Evaluation of blood gas, pH, Hct, and selected clinicopathologic variables provided useful clinical and prognostic information during rehabilitation of cold-stunned Kemp's ridley turtles.

Correlation between NM23 protein overexpression and prognostic value and clinicopathologic features of ovarian cancer: a meta-analysis.

PubMed

Fang, Jie; Guo, Xueke; Zheng, Bo; Han, Wei; Chen, Xia; Zhu, Jiawei; Xie, Bing; Liu, Jiajia; Luan, Xiaojin; Yan, Yidan; He, Zeyu; Li, Hong; Qiao, Chen; Yu, Jun

2018-02-01

The prognostic value and clinicopathological features of NM23 (non-metastasis 23) have previously been assessed, but the results are controversial. Here, we attempted to clarify the correlation between NM23 expression and its prognostic value and the clinicopathological features in ovarian cancer (OC). The relevant studies were identified using PubMed, Embase, and Web of Science. We calculated the pooled odds ratio (OR) with 95% confidence intervals (CIs) for overall survival (OS), progression-free survival (PFS), and clinicopathological features. We used OS to evaluate the prognostic value of NM23 expression in patients with OC. Subgroup analyses were used to explore the source of heterogeneity. We included 10 studies involving 894 patients in our assessment of the association between NM23 expression and OS for OC. Our data indicated that NM23 expression was not associated with improved OS (OR 0.83, 95% CI 0.41-1.68, P = 0.61) or PFS (OR 0.7, 95% CI 0.39-1.24, P = 0.22). Elevated NM23 expression was associated with differentiation grade (OR 0.35, 95% CI 0.2-0.6, P = 0.0002) and N status (OR 0.33, 95% CI 0.14-0.78, P = 0.01), whereas there was no significant difference between NM23 expression and tumor stage (OR 1.1, 95% CI 0.45-2.66, P = 0.84). Subgroup analysis did not reveal any potential source of heterogeneity. No obvious publication bias was found. In OC, there is poor statistical significance between NM23 expression and OS and PFS, but NM23 expression is related to differentiation grade and N status. This meta-analysis reveals that NM23 expression is a potential factor of poor prognosis in OC. The prognostic role of NM23 in different OC stages in combination with the clinical characteristics suggests a novel approach for developing future therapeutic targets.

Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias.

PubMed

Beecham, Gary W; Hamilton, Kara; Naj, Adam C; Martin, Eden R; Huentelman, Matt; Myers, Amanda J; Corneveaux, Jason J; Hardy, John; Vonsattel, Jean-Paul; Younkin, Steven G; Bennett, David A; De Jager, Philip L; Larson, Eric B; Crane, Paul K; Kamboh, M Ilyas; Kofler, Julia K; Mash, Deborah C; Duque, Linda; Gilbert, John R; Gwirtsman, Harry; Buxbaum, Joseph D; Kramer, Patricia; Dickson, Dennis W; Farrer, Lindsay A; Frosch, Matthew P; Ghetti, Bernardino; Haines, Jonathan L; Hyman, Bradley T; Kukull, Walter A; Mayeux, Richard P; Pericak-Vance, Margaret A; Schneider, Julie A; Trojanowski, John Q; Reiman, Eric M; Schellenberg, Gerard D; Montine, Thomas J

2014-09-01

Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related dementias.

The prognostic and clinicopathologic characteristics of CD147 and esophagus cancer: A meta-analysis.

PubMed

Li, Hui; Jiang, Chunxiang; Wu, Dongwen; Shi, Shupeng; Liao, Mengting; Wang, Jing; Li, Yanwen; Xu, Zihao

2017-01-01

The prognostic significance of CD147 expression in esophageal cancer patients remains controversial. Using a meta-analysis, we investigated the prognostic and clinicopathologic characteristics of CD147 in esophageal cancer. A comprehensive literature search of the PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wanfang databases (1988-2016) was performed to identify studies of all esophageal cancer subtypes. Correlations between CD147 expression and survival outcomes and clinicopathological features were analyzed using meta-analysis methods. Seventeen studies were included. High CD147 expression reduced the 3-year survival rate (OR = 3.26, 95% CI = (1.53, 6.93), p = 0.02) and 5-year survival rate(OR = 4.35, 95% CI = (2.13, 8.90), p < 0.0001). High CD147 expression reduced overall survival in esophageal cancer (HR = 1.60, 95% CI = (1.19, 2.15), p = 0.02). Additionally, higher CD147 expression was detected in esophageal cancer tissues than noncancerous tissues (OR = 9.45, 95% CI = (5.39, 16.59), p < 0.00001), normal tissues (OR = 12.73, 95% CI = (3.49, 46.46), p = 0.0001), para-carcinoma tissues (OR = 12.80, 95% CI = (6.57, 24.92), p < 0.00001), and hyperplastic tissues (OR = 3.27, 95% CI = (1.47, 7.29), p = 0.004). CD147 expression was associated with TNM stage (OR = 3.66, 95% CI = (2.20, 6.09), p < 0.00001), tumor depth (OR = 7.97, 95% CI = (4.13, 15.38), p < 0.00001), and lymph node status (OR = 5.14, 95% CI = (2.03,13.01), p = 0.0005), but not with tumor differentiation, age, or sex. Our meta-analysis suggests that CD147 is an efficient prognostic factor in esophageal cancer. High CD147 expression in patients with esophageal cancer was associated with worse survival outcomes and common clinicopathological indicators of poor prognosis.

Marginal and joint distributions of S100, HMB-45, and Melan-A across a large series of cutaneous melanomas.

PubMed

Viray, Hollis; Bradley, William R; Schalper, Kurt A; Rimm, David L; Gould Rothberg, Bonnie E

2013-08-01

The distribution of the standard melanoma antibodies S100, HMB-45, and Melan-A has been extensively studied. Yet, the overlap in their expression is less well characterized. To determine the joint distributions of the classic melanoma markers and to determine if classification according to joint antigen expression has prognostic relevance. S100, HMB-45, and Melan-A were assayed by immunofluorescence-based immunohistochemistry on a large tissue microarray of 212 cutaneous melanoma primary tumors and 341 metastases. Positive expression for each antigen required display of immunoreactivity for at least 25% of melanoma cells. Marginal and joint distributions were determined across all markers. Bivariate associations with established clinicopathologic covariates and melanoma-specific survival analyses were conducted. Of 322 assayable melanomas, 295 (91.6%), 203 (63.0%), and 236 (73.3%) stained with S100, HMB-45, and Melan-A, respectively. Twenty-seven melanomas, representing a diverse set of histopathologic profiles, were S100 negative. Coexpression of all 3 antibodies was observed in 160 melanomas (49.7%). Intensity of endogenous melanin pigment did not confound immunolabeling. Among primary tumors, associations with clinicopathologic parameters revealed a significant relationship only between HMB-45 and microsatellitosis (P = .02). No significant differences among clinicopathologic criteria were observed across the HMB-45/Melan-A joint distribution categories. Neither marginal HMB-45 (P = .56) nor Melan-A (P = .81), or their joint distributions (P = .88), was associated with melanoma-specific survival. Comprehensive characterization of the marginal and joint distributions for S100, HMB-45, and Melan-A across a large series of cutaneous melanomas revealed diversity of expression across this group of antigens. However, these immunohistochemically defined subclasses of melanomas do not significantly differ according to clinicopathologic correlates or outcome.

Oral cancer prognosis based on clinicopathologic and genomic markers using a hybrid of feature selection and machine learning methods

PubMed Central

2013-01-01

Background Machine learning techniques are becoming useful as an alternative approach to conventional medical diagnosis or prognosis as they are good for handling noisy and incomplete data, and significant results can be attained despite a small sample size. Traditionally, clinicians make prognostic decisions based on clinicopathologic markers. However, it is not easy for the most skilful clinician to come out with an accurate prognosis by using these markers alone. Thus, there is a need to use genomic markers to improve the accuracy of prognosis. The main aim of this research is to apply a hybrid of feature selection and machine learning methods in oral cancer prognosis based on the parameters of the correlation of clinicopathologic and genomic markers. Results In the first stage of this research, five feature selection methods have been proposed and experimented on the oral cancer prognosis dataset. In the second stage, the model with the features selected from each feature selection methods are tested on the proposed classifiers. Four types of classifiers are chosen; these are namely, ANFIS, artificial neural network, support vector machine and logistic regression. A k-fold cross-validation is implemented on all types of classifiers due to the small sample size. The hybrid model of ReliefF-GA-ANFIS with 3-input features of drink, invasion and p63 achieved the best accuracy (accuracy = 93.81%; AUC = 0.90) for the oral cancer prognosis. Conclusions The results revealed that the prognosis is superior with the presence of both clinicopathologic and genomic markers. The selected features can be investigated further to validate the potential of becoming as significant prognostic signature in the oral cancer studies. PMID:23725313

Improved prediction of biochemical recurrence after radical prostatectomy by genetic polymorphisms.

PubMed

Morote, Juan; Del Amo, Jokin; Borque, Angel; Ars, Elisabet; Hernández, Carlos; Herranz, Felipe; Arruza, Antonio; Llarena, Roberto; Planas, Jacques; Viso, María J; Palou, Joan; Raventós, Carles X; Tejedor, Diego; Artieda, Marta; Simón, Laureano; Martínez, Antonio; Rioja, Luis A

2010-08-01

Single nucleotide polymorphisms are inherited genetic variations that can predispose or protect individuals against clinical events. We hypothesized that single nucleotide polymorphism profiling may improve the prediction of biochemical recurrence after radical prostatectomy. We performed a retrospective, multi-institutional study of 703 patients treated with radical prostatectomy for clinically localized prostate cancer who had at least 5 years of followup after surgery. All patients were genotyped for 83 prostate cancer related single nucleotide polymorphisms using a low density oligonucleotide microarray. Baseline clinicopathological variables and single nucleotide polymorphisms were analyzed to predict biochemical recurrence within 5 years using stepwise logistic regression. Discrimination was measured by ROC curve AUC, specificity, sensitivity, predictive values, net reclassification improvement and integrated discrimination index. The overall biochemical recurrence rate was 35%. The model with the best fit combined 8 covariates, including the 5 clinicopathological variables prostate specific antigen, Gleason score, pathological stage, lymph node involvement and margin status, and 3 single nucleotide polymorphisms at the KLK2, SULT1A1 and TLR4 genes. Model predictive power was defined by 80% positive predictive value, 74% negative predictive value and an AUC of 0.78. The model based on clinicopathological variables plus single nucleotide polymorphisms showed significant improvement over the model without single nucleotide polymorphisms, as indicated by 23.3% net reclassification improvement (p = 0.003), integrated discrimination index (p <0.001) and likelihood ratio test (p <0.001). Internal validation proved model robustness (bootstrap corrected AUC 0.78, range 0.74 to 0.82). The calibration plot showed close agreement between biochemical recurrence observed and predicted probabilities. Predicting biochemical recurrence after radical prostatectomy based on clinicopathological data can be significantly improved by including patient genetic information. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

The Role of p-STAT3 as a Prognostic and Clinicopathological Marker in Colorectal Cancer: A Systematic Review and Meta-Analysis

PubMed Central

Chu, Qi; Gan, Yong; Ren, Hui; Zhang, Liyan; Wang, Liwei; Li, Xiaoxiu; Wang, Wei

2016-01-01

Objective High expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) has been detected in a variety of human tumors. However, the association of positive p-STAT3 expression with clinicopathological parameters and the prognosis of colorectal cancer patients remain controversial. To identify the relationship between p-STAT3 expression and clinicopathological parameters and prognosis in patients with colorectal cancer, a systematic review and meta-analysis were performed. Methods We performed a comprehensive literature search from PubMed, EMBASE, and SinoMed through 27 March, 2016. Hazard ratios (HRs) with 95% confidence intervals (CI) were combined to evaluate the association between p-STAT3 expression and overall survival of colorectal cancer patients. Odds ratios (ORs) with 95% CI were combined to evaluate the association between p-STAT3 expression and clinicopathological parameters in patients with colorectal cancer. Results Seventeen studies including a total of 2,346 colorectal cancer patients were included in this meta-analysis. The combined HR was 1.43 (95% CI: 1.23–1.67, P < 0.001), which suggested a positive relationship between p-STAT3 overexpression and poorer overall survival of colorectal cancer patients. In addition, the results indicated that positive p-STAT3 expression was significantly associated with the presence of lymph node metastasis (OR: 2.43, 95% CI: 1.18–5.01, P = 0.02) but was not associated with TNM stage, tumor differentiation or gender. Conclusion The meta-analysis results suggest that p-STAT3 overexpression is unfavorable for the prognosis of colorectal cancer patients, and p-STAT3 overexpression is associated with the presence of lymph node metastasis among colorectal cancer patients. PMID:27504822

Genetic progression in microsatellite instability high (MSI-H) colon cancers correlates with clinico-pathological parameters: A study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes.

PubMed

Calin, G A; Gafà, R; Tibiletti, M G; Herlea, V; Becheanu, G; Cavazzini, L; Barbanti-Brodano, G; Nenci, I; Negrini, M; Lanza, G

2000-05-20

Colon carcinomas with microsatellite mutator phenotype exhibit specific genetic and clinico-pathological features. This report describes the analysis of 63 "microsatellite instability-high" (MSI-H) tumors for the presence of mutations in microsatellites located in the coding regions (CDRs) of 6 genes: TGFbetaRII, BAX, hMSH3, hMSH6, IGFIIR, and BLM. The following frequencies of mutations were detected: TGFbetaRII (70%), BAX (54%), hMSH3 (36.5%), IGFIIR (22%), hMSH6 (17.5%), and BLM (16%). The overall picture revealed combinations of mutations suggestive of a progressive order of accumulation, with mutations of TGFbetaRII and BAX first, followed by frameshifts in hMSH3, hMSH6, IGFIIR, and BLM. Correlations with 12 clinico-pathological parameters revealed that tumors with frameshifts in 1 or 2 CDRs were significantly better differentiated than tumors with frameshifts in more than 2 CDRs. We also found that mutations in the hMSH3 gene were significantly associated with decreased wall invasiveness and aneuploidy, and frameshifts in the BLM gene were significantly associated with the mucinous histotype. A trend toward an association between hMSH3 and IGFIIR with the medullary and conventional adenocarcinoma histotypes, respectively, was seen. Our results strengthen the concept that mutations in target genes have a role in the tumorigenic process of MSI-H tumors, and indicate that frameshifts in microsatellites located in CDRs occur in a limited number of combinations that could determine distinct clinico-pathological traits. Copyright 2000 Wiley-Liss, Inc.

Insular and anaplastic carcinoma of the thyroid: a 45-year comparative study at a single institution and a review of the significance of p53 and p21.

PubMed

Lam, K Y; Lo, C Y; Chan, K W; Wan, K Y

2000-03-01

To analyze the clinicopathologic features of a large cohort of patients with insular or anaplastic carcinomas treated at a single institution. Insular and anaplastic carcinomas of the thyroid, although uncommon, have more aggressive clinical behavior than well-differentiated carcinomas of the thyroid. In the literature, the incidence and features of these carcinomas have not been fully characterized. The authors reclassified 740 primary thyroid carcinomas diagnosed and treated between January 1, 1954, and December 30, 1998, to select those with features that met the histologic criteria of insular or anaplastic carcinoma. The clinicopathologic features of these carcinomas were studied and compared. The expression of p53 and p21 in these tumors was analyzed by immunohistochemistry. Twenty-two patients (5 men, 17 women) with insular carcinoma and 38 patients (7 men, 31 women) with anaplastic carcinoma were found. Patients with insular carcinomas were younger (mean age 45 vs. 70 years) and had smaller tumors than those with anaplastic carcinomas (mean diameter 5 vs. 8 cm). Insular carcinomas were commonly mislabeled as other histologic subtypes, whereas anaplastic carcinomas might be overdiagnosed on pathologic examination. A history of longstanding goiter (>10 years) was noted in 27% of patients with insular carcinoma and 24% of patients with anaplastic carcinomas. Concomitant well-differentiated carcinomas of the thyroid were noted in 59% of patients with insular carcinoma and 39% of patients with anaplastic carcinoma. In anaplastic carcinomas, 13% of patients had concomitant insular carcinoma. Calcification or bone was noted in the stroma of 23% of patients with insular carcinomas and 47% of those with anaplastic carcinomas. The 10-year survival rates for patients with insular carcinoma and anaplastic carcinoma were 42% and 3%, respectively. Distant metastases were seen in 32% of patients with insular carcinoma and in 47% of patients with anaplastic carcinomas. In both types of carcinomas, metastatic tumors were often seen in bone and lung. Distant metastases were noted in a variety of organs in anaplastic carcinomas. In insular carcinoma, neither p53 nor p21 expression was present. In anaplastic carcinoma, p53 and p21 expression was identified in 69% and 3%, respectively. Concomitant expression of p53 and p21 was noted in one tumor. Insular carcinoma and anaplastic carcinoma had distinctive clinicopathologic features, and recognition of these histologic variants is important for better management of these tumors in the future. p53 overexpression might have a role in dedifferentiation from insular carcinoma to anaplastic carcinoma.

Necrotizing infundibular crystalline folliculitis: a clinicopathological study.

PubMed

Denisjuk, Natalja; Hilty, Norbert; Pfaltz, Madeleine; Kempf, Werner

2012-05-01

Necrotizing infundibular crystalline folliculitis (NICF) is a folliculocentric disorder associated with filamentous crystalline deposits, enclosed by parakeratotic columns within the partly necrotic follicular ostium and infundibulum. There are only very few data published about this disorder of unknown origin. We sought to determine the clinicopathological features and pathogenetic aspects of NICF. Clinicopathological characterization of 9 patients with NICF and a second group of 7 patients with coincidental findings of NICF in the vicinity of epithelial skin neoplasms was conducted. Clinically, NICF is characterized by multiple waxy papules with predilection for the forehead (56%), neck, and back. Birefringent crystalline deposits were present in the follicular ostia and enclosed by parakeratotic columns in all cases. The necrosis of follicular epithelium was found in 89% and perifollicular neutrophilic infiltrate in 22% of the biopsy specimens. Both yeasts and gram-positive bacteria were identified within the affected follicles in 56% in the first group and 86% in the second group of coincidental NICF. This was a single-center retrospective study. NICF is both a distinct entity and an epiphenomenon in the context of other disorders. In regard to the common association with yeasts and gram-positive bacteria in the affected follicles, we hypothesize that NICF is pathogenetically linked to these organisms, which is supported by resolution of the lesions after topical or systemic antimycotic treatment. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Hematologic and plasma biochemical changes associated with fenbendazole administration in Hermann's tortoises (testudo hermanni).

PubMed

Neiffer, Donald L; Lydick, Dianna; Burks, Kyle; Doherty, Donna

2005-12-01

Toxicosis associated with benzimidazole anthelmintics has been reported with increasing frequency in zoologic collections. Clinical signs, clinicopathologic abnormalities, and gross and histologic lesions are primarily the result of damage to the gastrointestinal and hematopoietic systems. Profound leukopenia, especially granulocytopenia, is the most common and severe clinicopathologic change associated with benzimidazole administration. Death usually occurs from overwhelming systemic bacterial and/or fungal infections secondary to severe immunosuppression. In this 125-day study, six male Hermann's tortoises (Testudo hermanni) were treated orally with two 5-day courses of fenbendazole 2 wk apart at a dosage of 50 mg/kg. Serial blood samples were used to assess hematologic and plasma biochemical changes before, during, and following the treatment period. Although the tortoises remained healthy, blood sampling indicated an extended heteropenia with transient hypoglycemia, hyperuricemia, hyperphosphatemia, and equivocal hyperproteinemia/hyperglobulinemia, which were considered to be in response to fenbendazole administration. Changes in several other clinicopathologic parameters appeared to correlate with fenbendazole administration. The hematologic and biochemical changes seen in the healthy animals in this study should be considered when treating compromised tortoises with fenbendazole. Hematologic and plasma biochemical status of tortoises/reptiles should be determined before treatment and monitored during the treatment period. The risk of mortality of an individual from nematode infection should be assessed relative to the potential for metabolic alteration and secondary septicemia following damage to hematopoietic and gastrointestinal systems by fenbendazole.

Cytokeratin 5/6 and cytokeratin 8/18 expression in triple negative breast cancers: clinicopathologic significance in South-Asian population.

PubMed

Hashmi, Atif Ali; Naz, Samreen; Hashmi, Shumaila Kanwal; Hussain, Zubaida Fida; Irfan, Muhammad; Bakar, Syed Muhammad Abu; Faridi, Naveen; Khan, Amir; Edhi, Muhammad Muzzammil

2018-06-08

Cytokeratin 5/6 and Cytokeratin 8/18 are basal and luminal markers of breast cancer and they have pathological and prognostic significance in breast cancer. We performed Cytokeratin 5/6 and CK8/18 immunohistochemistry on 150 cases of triple negative breast cancers and association with various clinicopathological features was evaluated. Positive CK5/6 expression was noted in 8% (12 cases) of TNBC while 2.4% (4 cases) showed focal positive (< 10%) and 89.3% (134) were negative with CK5/6. Complete loss of CK8/18 expression was seen in 4.7% (7 cases) while 32.7% (49 cases) revealed focal loss of CK8/18 and 62.7% (94 cases) showed intact normal expression of CK8/18. No significant association of CK5/6 and CK8/18 with various clinicopathological parameters was observed. We found a low expression of basal cytokeratin (CK5/6) in TNBC our studied population, while loss/altered expression of CK8/18 in approximately 38% of TNBC. Although no prognostic relevance of these finding was noted in our study, however these findings are different from those reported in literature in other parts of the world. Therefore we suggest a more through immunohistochemical and genomic profiling of TNBC in our population for better understanding of this disease in this part of the world.

Overall accuracy of cervical cytology and clinicopathological significance of LSIL cells in ASC-H cytology.

PubMed

Kim, S H; Lee, J M; Yun, H G; Park, U S; Hwang, S U; Pyo, J-S; Sohn, J H

2017-02-01

The aims of this study were (i) to investigate the diagnostic accuracy of Papanicolaou (Pap) smears and (ii) to evaluate the clinicopathological significance of the presence of low-grade squamous intraepithelial lesion (LSIL) cells in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) cytology. We retrospectively reviewed paired cytological and histological findings from 3141 patients. ASC-H cytology was classified as either ASC-H or LSIL with some features suggestive of the presence of a concurrent HSIL (LSIL-H). Clinicopathological characteristics were evaluated through a retrospective study and meta-analysis. The accuracy of the cytological diagnosis was 93.7% (2942 of 3141 cases). The positive predictive value (PPV) of ASC-H for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+ ) was 51.4%. In cases of LSIL-H, CIN 2+ histology was more prevalent in the pre-menopausal period (19-44 years) than in peri- and postmenopausal periods (older than 45 years) (P = 0.024). There was no difference in the ability of LSIL-H and ASC-H to predict CIN 2+. The Pap smear is a good cervical cancer screening method. Although there was no difference in the predictive value for CIN 2+ between LSIL-H and ASC-H, the presence of definite LSIL cells was more predictive of CIN 2+ in younger patients than in older patients. © 2016 John Wiley & Sons Ltd.

Identifying molecular subtypes related to clinicopathologic factors in pancreatic cancer

PubMed Central

2014-01-01

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal tumors and usually presented with locally advanced and distant metastasis disease, which prevent curative resection or treatments. In this regard, we considered identifying molecular subtypes associated with clinicopathological factor as prognosis factors to stratify PDAC for appropriate treatment of patients. Results In this study, we identified three molecular subtypes which were significant on survival time and metastasis. We also identified significant genes and enriched pathways represented for each molecular subtype. Considering R0 resection patients included in each subtype, metastasis and survival times are significantly associated with subtype 1 and subtype 2. Conclusions We observed three PDAC molecular subtypes and demonstrated that those subtypes were significantly related with metastasis and survival time. The study may have utility in stratifying patients for cancer treatment. PMID:25560450

[Detection of ALK, ROS1 and RET fusion genes in non-small cell lung cancer patients and its clinicopathologic correlation].

PubMed

Zhong, Shan; Zhang, Haiping; Bai, Dongyu; Gao, Dehong; Zheng, Jie; Ding, Yi

2015-09-01

To study the prevalence of ALK, ROS1 and RET fusion genes in non-small cell lung cancer (NSCLC), and its correlation with clinicopathologic features. Formalin-fixed and paraffin-embedded tissue sections from samples of 302 patients with NSCLC were screened for ALK, ROS1, RET fusions by real-time polymerase chain reaction (PCR). All of the cases were validated by Sanger DNA sequencing. The relationship between ALK, ROS1, RET fusion genes and clinicopathologic features were analyzed. In the cohort of 302 NSCLC samples, 3.97% (12/302) were found to contain ALK fusion genes, including 3 cases with E13; A20 gene fusion, 3 cases with E6; A20 gene fusion and 3 cases with E20; A20 gene fusion. There was no statistically significant difference in patient's gender, age, smoking history and histologic type. Moreover, in the 302 NSCLC samples studied, 3.97% (12/302) were found to contain ROS1 fusion genes, with CD74-ROS1 fusion identified in 9 cases. There was no statistically significant difference in patients' gender, age, smoking history and histologic type. One non-smoking elderly female patient with pulmonary adenocarcinoma had RET gene fusion. None of the cases studied had concurrent ALK, ROS1 and RET mutations. The ALK, ROS1 and RET fusion gene mutation rates in NSCLC are low, they represent some specific molecular subtypes of NSCLC. Genetic testing has significant meaning to guide clinical targeted therapy.

Actinic cheilitis: clinicopathologic profile and association with degree of dysplasia.

PubMed

de Santana Sarmento, Dmitry José; da Costa Miguel, Márcia Cristina; Queiroz, Lélia Maria Guedes; Godoy, Gustavo Pina; da Silveira, Ericka Janine Dantas

2014-04-01

Actinic cheilitis (AC) is a potentially malignant disorder of the lip caused by exposure to solar radiation. This study was conducted to evaluate the clinicopathologic profile of cases of AC and to verify associations with the degree of dysplasia. This retrospective study analyzed data for 40 patients with AC. Demographic, clinical, and histopathologic data were evaluated. Sections measuring 5 μm in thickness were cut, deparaffinized, and stained with hematoxylin and eosin for histologic examination. The degree of epithelial dysplasia was graded using the criteria defined by the World Health Organization. Two calibrated oral pathologists analyzed the slides. Analysis of the AC patients sampled showed that 75.0% were male (P=0.002), 80.0% were aged≥40 years (P<0.001), 74.3% were Caucasian (P=0.004), and 68.6% had occupational exposure to sunlight (P=0.028). The most common clinical manifestation was white lesions (55.0%), and 40.0% of patients had no dysplasia. No significant associations emerged between the histologic grading of AC and gender (P=1.000), age (P=1.000), ethnicity (P=0.416), occupational exposure to sunlight (P=1.000), and clinical presentation (P=0.467). The degree of dysplasia in AC was not statistically associated with gender, age, ethnicity, occupational exposure to sunlight, or clinical appearance. This study provides some support for the hypothesis that clinicopathologic features are not related to the degree of dysplasia in AC. © 2013 The International Society of Dermatology.

Alveolar ridge keratosis - a retrospective clinicopathological study

PubMed Central

2013-01-01

Background Alveolar ridge keratosis (ARK) is a distinct, benign clinicopathological entity, characterized by a hyperkeratotic plaque or patch that occurs on the alveolar edentulous ridge or on the retromolar trigone, considered to be caused by chronic frictional trauma. The aim of this retrospective study is to present the clinicopathological features of 23 consecutive cases of ARK. Material and methods The 23 biopsy samples of ARK were selected and pathological features were revised (keratosis, acanthosis, surface architecture, and inflammation). Factors such as the patient’s gender, age, anatomical location, tobacco and alcohol use were analyzed. Results Sixteen out of the 23 cases studied were men and 7 women with a mean age of 55.05 (age ranged from 17 to 88 years). Thirteen cases had a history of tobacco habit, amongst whom, 4 also presented alcohol consumption. All the cases presented only unilateral lesions. Nineteen cases involved the retromolar trigone while 4 cases involved edentulous alveolar ridges. When observed microscopically, the lesions were mainly characterized by moderate to important hyperorthokeratosis. Inflammation was scanty or absent. In four of the cases, the presence of melanin pigment in the superficial corium or in the cytoplasm of macrophages was detected. None of the cases showed any features of dysplasia. Conclusion Our results reveal that ARK is a benign lesion. However, the high prevalence of smokers amongst the patients might suggest that some potentially malignant disorders such as tobacco associated leukoplakia may clinically mimic ARK. PMID:23587097

Clinicopathological analysis of 12 patients with Epstein-Barr virus-positive primary intestinal T/natural killer-cell lymphoma (EBV+ ITNKL).

PubMed

Hu, Lei-Ming; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Asano, Naoko; Takahashi, Emiko; Furukawa, Katsuya; Miyoshi, Hiroaki; Satou, Akira; Kohno, Kei; Kosugi, Hiroshi; Kinoshita, Tomohiro; Hirooka, Yoshiki; Goto, Hidemi; Nakamura, Shigeo; Kato, Seiichi

2017-06-01

Epstein-Barr virus-positive (EBV + ) intestinal T/natural killer (NK) cell lymphoma (ITNKL) is an uncommon tumour with an extremely aggressive clinical behaviour. However, the clinicopathological characteristics of this tumour, including T cell receptor (TCR) phenotype and the patient's background, remain unknown. The aim of this study was to elucidate the detailed clinicopathological profile of EBV + ITNKL. We enrolled 12 patients with EBV + ITNKL without nasal involvement into the study. All patients were characterized by involvement of the small intestine with concurrent lesions of the large intestine in two patients. Seven patients (58%) had Lugano stages IIE/IV disease and eight (67%) were categorized as high-intermediate/high-risk according to the Prognostic Index for PTCL (PIT). Three patients (25%) with an age of onset of less than 50 years had chronic active EBV infection (CAEBV). Five CD56-positive patients (42%) had a poorer prognosis than those without CD56 expression (P = 0.008). NK cell-type lymphoma defined by the absence of any TCR expression or clonal TCR-γ rearrangement was found in six patients (50%). Interestingly, EBV + intra-epithelial lymphocytosis was observed in one case with a background of CAEBV. This study is the first to shed light on the significant heterogeneity of EBV + ITNKL and its relationship with CAEBV, especially in patients younger than 50 years of age. These observations will provide a guide for diagnostic and therapeutic approaches in routine practice. © 2017 John Wiley & Sons Ltd.

Prevalence of Enhancer of Zeste Homolog 2 in Patients with Resected Small Cell Lung Cancer.

PubMed

Toyokawa, Gouji; Takada, Kazuki; Tagawa, Tetsuzo; Kinoshita, Fumihiko; Kozuma, Yuka; Matsubara, Taichi; Haratake, Naoki; Takamori, Shinkichi; Akamine, Takaki; Hirai, Fumihiko; Yamada, Yuichi; Hamamoto, Ryuji; Oda, Yoshinao; Maehara, Yoshihiko

2018-06-01

Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is deeply involved in cancer pathogenesis. Although clinicopathological significance of EZH2 in non-small cell lung cancer has been gradually elucidated, such significance in small cell lung cancer (SCLC) has yet to be fully investigated. Forty patients with resected SCLC were analyzed for EZH2. EZH2 expression was evaluated using the Allred score (0-8) and was classified into negative (0-6) and positive (7 and 8). We evaluated the association between EZH2 and the clinicopathological characteristics and postoperative survivals. Among 40 patients, 15 (37.5%) and 25 (62.5%) were classified as being negative and positive for EZH2, respectively. Fisher's exact test demonstrated no significant associations between the positivity for EZH2 and clinicopathological characteristics. No significant differences were observed in recurrence-free and overall survivals between EZH2-negative/low and EZH2-high patients. EZH2 was frequently observed in patients with resected SCLC, but no significant associations were found between its expression and the clinicopathological characteristics and postoperative survivals. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

CCR4 frameshift mutation identifies a distinct group of adult T cell leukaemia/lymphoma with poor prognosis.

PubMed

Yoshida, Noriaki; Miyoshi, Hiroaki; Kato, Takeharu; Sakata-Yanagimoto, Mamiko; Niino, Daisuke; Taniguchi, Hiroaki; Moriuchi, Yukiyoshi; Miyahara, Masaharu; Kurita, Daisuke; Sasaki, Yuya; Shimono, Joji; Kawamoto, Keisuke; Utsunomiya, Atae; Imaizumi, Yoshitaka; Seto, Masao; Ohshima, Koichi

2016-04-01

Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Histone deacetylase (HDAC)-1, -2, -4 and -6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.

PubMed

Giaginis, Constantinos; Damaskos, Christos; Koutsounas, Ioannis; Zizi-Serbetzoglou, Adamantia; Tsoukalas, Nicolaos; Patsouris, Efstratios; Kouraklis, Gregorios; Theocharis, Stamatios

2015-10-26

Histone deacetylases (HDACs) have been associated with malignant tumor development and progression in humans. HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, -2, -4 and -6 protein expression in pancreatic adenocarcinoma. HDAC-1, -2, -4 and -6 protein expression was assessed immunohistochemically on 70 pancreatic adenocarcinoma tissue specimens and was statistically analyzed with clinicopathological characteristics and patients' survival. Enhanced HDAC-1 expression was significantly associated with increased tumor proliferative capacity (p = 0.0238) and borderline with the absence of lymph node metastases (p = 0.0632). Elevated HDAC-4 expression was significantly associated with the absence of organ metastases (p = 0.0453) and borderline with the absence of lymph node metastases (p = 0.0571) and tumor proliferative capacity (p = 0.0576). Enhanced HDAC-6 expression was significantly associated with earlier histopathological stage (p = 0.0115) and borderline with smaller tumor size (p = 0.0864). Pancreatic adenocarcinoma patients with enhanced HDAC-1 and -6 expression showed significantly longer survival times compared to those with low expression (p = 0.0022 and p = 0.0113, respectively), while a borderline association concerning HDAC-2 expression was noted (p = 0.0634). The present study suggested that HDACs may be implicated in pancreatic malignant disease progression, being considered of clinical utility with potential use as therapeutic targets.

The role of the CpG island methylator phenotype on survival outcome in colon cancer.

PubMed

Kang, Ki Joo; Min, Byung Hoon; Ryu, Kyung Ju; Kim, Kyoung Mee; Chang, Dong Kyung; Kim, Jae J; Rhee, Jong Chul; Kim, Young Ho

2015-03-01

CpG island methylator phenotype (CIMP)- high colorectal cancers (CRCs) have distinct clinicopathologi-cal features from their CIMP-low/negative CRC counterparts. However, controversy exists regarding the prognosis of CRC according to the CIMP status. Therefore, this study examined the prognosis of Korean patients with colon cancer according to the CIMP status. Among a previous cohort pop-ulation with CRC, a total of 154 patients with colon cancer who had available tissue for DNA extraction were included in the study. CIMP-high was defined as ≥3/5 methylated mark-ers using the five-marker panel (CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1). CIMP-high and CIMP-low/neg-ative cancers were observed in 27 patients (17.5%) and 127 patients (82.5%), respectively. Multivariate analysis adjust-ing for age, gender, tumor location, tumor stage and CIMP and microsatellite instability (MSI) statuses indicated that CIMP-high colon cancers were associated with a significant increase in colon cancer-specific mortality (hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.20 to 8.69; p=0.02). In microsatellite stable cancers, CIMP-high cancer had a poor survival outcome compared to CIMP-low/negative cancer (HR, 2.91; 95% CI, 1.02 to 8.27; p=0.04). Re-gardless of the MSI status, CIMP-high cancers had poor sur-vival outcomes in Korean patients. (Gut Liver, 2015;9202-207).

Analysis and significance of c-MET expression in adenoid cystic carcinoma of the salivary gland.

PubMed

Bell, Diana; Ferrarotto, Renata; Fox, Melanie D; Roberts, Dianna; Hanna, Ehab Y; Weber, Randal S; El-Naggar, Adel K

2015-01-01

Adenoid cystic carcinoma (ACC), a rare salivary gland malignancy, is a histogenetic, morphologic, and clinical heterogeneous disease. Extensive efforts have been made to characterize molecular events associated with these tumors, including the identification of prognostic and predictive biomarkers. Increased copy number gain and amplification of c-Met, the cell surface receptor for hepatocyte growth factor, has been shown to enhance tumor growth and invasiveness and promote metastasis in certain tumor types. In this study, we evaluated the expression of c-Met by immunohistochemistry (IHC) in a large cohort of salivary gland ACCs and examined its clinicopathologic implications. Archival formalin-fixed paraffin-embedded blocks from 200 ACC patients were used in this study. Pathologic patterns and phenotypic expression of c-Met were recorded and compared with clinical factors including gender, age, disease stage at diagnosis, and clinical outcomes. Correlations between c-MET expression and clinical characteristics were assessed by Pearson's chi-square test or by the 2-tailed Fisher exact test. Curves describing overall survival were generated by Kaplan-Meier product limit method. Strong c-MET expression was seen in inner ductal and outer myoepithelial cells in 53.2% of the cases. There was no correlation between c-Met overexpression and clinicopathologic parameters or patient's overall survival ( p = .94074). In conclusion, c-MET expression is high in a significant subgroup of ACC patients. While c-MET expression is not a prognostic factor in ACC, its role as a predictive marker of benefit from MET inhibitors deserves further investigation.

Impact of Hepatitis B Virus on Clinicopathological Features and Outcomes After Resection for Pancreatic Adenocarcinoma.

PubMed

Dumitrascu, Traian; Pineau, Pascal; Dima, Simona; Stroescu, Cezar; Brasoveanu, Vladislav; Herlea, Vlad; Ionescu, Mihnea; Popescu, Irinel

2015-09-01

Background/ Aim: Chronic hepatitis B virus (HBV) infection is sometimes considered a risk factor for pancreatic cancer (PDAC), but the prognostic value of its presence has only rarely been investigated. The present study aimed to explore the impact of HBV after resection for PDAC. According to HBV surface antigen seroreactivity, 343 patients were classified as having non-viral or HBV-related cases of PDAC. Clinicopathological data and outcomes were comparatively assessed between the groups. Chronic HBV infection was observed in 16 patients (4.5%). No significant differences between the HBV and non-viral cases of PDAC were observed. Tumor diameters (3.4 vs. 3.0, p=0.092) and stages at diagnosis (31 vs. 14% T1-T2, p=0.082) tended to differ between the groups, albeit without reaching significance. Completion of adjuvant therapy (63 vs. 54%, p=0.612), as well as median overall survival (15 vs. 17 months, p=0.346) was similar in the HBV and non-viral PDAC groups. HBV-positive and virus-free patients with PDAC generally shared the same demographic, clinical and pathological profiles. HBV did not appear to have a detrimental effect on either early or long-term outcomes after resection for PDAC. Future studies searching for occult infection might, however, shed a different light on the role of HBV in PDAC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Expression and clinicopathological significance of microRNA-21 and programmed cell death 4 in malignant melanoma.

PubMed

Jiao, Jian; Fan, Yu; Zhang, Yan

2015-10-01

To measure levels of microRNA (miR)-21 and its target gene, programmed cell death 4 (PDCD4), in samples of human cutaneous malignant melanoma and normal non-malignant control skin. Relative levels of miR-21 and PDCD4 mRNA were measured using a quantitative real-time reverse transcription-polymerase chain reaction. Correlations between the levels of the two molecules and the clinicopathological characteristics of malignant melanoma were analysed. A total of 67 cases of human cutaneous malignant melanoma were analysed and compared with 67 samples of normal nonmalignant control skin. Compared with normal skin samples, the relative level of miR-21 was significantly higher and the relative level of PDCD4 mRNA was significantly lower in the melanoma specimens. A significant negative correlation between PDCD4 mRNA and miR-21 was demonstrated in malignant melanoma (r = -0.602). Elevated miR-21 and reduced PDCD4 mRNA levels were both significantly correlated with increased tumour size, a higher Clark classification level and the presence of lymph node metastases in malignant melanoma. These findings suggest that miR-21 and PDCD4 might be potential biomarkers for malignant melanoma and might provide treatment targets in the future. © The Author(s) 2015.

ABO Blood Group and Endometrial Carcinoma: A Preliminary Single-Center Experience from Saudi Arabia.

PubMed

Abu-Zaid, Ahmed; Alsabban, Mohannad; Abuzaid, Mohammed; Alomar, Osama; Al-Badawi, Ismail A; Salem, Hany

2017-12-18

Inherited ABO blood groups have been shown to play possible contributions in the pathogenesis of various gynecologic and non-gynecologic carcinomas. With regard to gynecologic carcinomas, there is a confined number of studies that explored the relationship between ABO blood group and endometrial carcinoma (EC) in the PubMed-indexed literature. To the best of our knowledge, no such study has ever been conducted in Saudi Arabia. Our study has two objectives: (I) to determine the prevalence of ABO blood groups among Saudi patients with EC, and (II) to explore the relationship between ABO blood group and several clinico-pathological prognostic parameters (namely: menopausal status [age], body mass index [BMI], tumor grade, FIGO [Fédération Internationale de Gynécologie et d'Obstétrique] stage and recurrence) in Saudi patients with EC. A retrospective cross-sectional study from 01-January-2010 to 31-July-2014 was conducted at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia - a referral tertiary healthcare institute. One-hundred and fourteen patients (n=114) were included in the study. Clinico-pathological data were extrapolated from medical records, and their association with ABO blood groups were evaluated. Categorical data were presented as number of cases (n) and percentages (%). Two-tailed Chi-square test was used for univariate analysis. For all purposes, p values <0.05 were regarded as statistically significant. The mean age and BMI were 59.5 ± 10.8 years (range: 31 - 90) and 36.6 ± 8.6 kg/m 2 (range: 17 - 60), respectively. The vast majority of patients were post-menopausal (86%), had BMI >28 kg/m 2 (84.2%), diagnosed with early FIGO stage I-II (76.3%) and developed no recurrence (86.8%). The frequencies of ABO blood group types A, B, AB, and O were 28.1%, 12.3%, 3.5% and 56.1%, respectively. When ABO blood groups were analyzed as four different types (A, B, AB and O), O-type was the most common ABO blood group in pre- and post-menopausal EC patients (43.8% and 58.2%, respectively; p=0.14). There were no statistically significant correlations between ABO blood groups and all the examined clinico-pathological factors. Moreover, when ABO blood groups were analyzed as two different types (O and non-O), similar results were obtained; no statistically significant correlations were found between ABO blood groups and all the examined clinico-pathological factors.  O-type was the most prevalent ABO blood group among Saudi Arabian patients with EC, and our finding was different from the existing literature, probably highlighting an ethnic-related variance. Furthermore, no statistically significant correlations were identified between ABO blood groups and all the examined clinico-pathological factors. Also, routine ABO blood group may emerge as a clinically accessible, beneficial and economical biomarker for a possible EC vulnerability. A large-sized case-control study is needed to withdraw solid conclusions.

Collagen Triple Helix Repeat Containing-1 (CTHRC1) Expression in Oral Squamous Cell Carcinoma (OSCC): Prognostic Value and Clinico-Pathological Implications

PubMed Central

Lee, Chia Ee; Vincent-Chong, Vui King; Ramanathan, Anand; Kallarakkal, Thomas George; Karen-Ng, Lee Peng; Ghani, Wan Maria Nabillah; Rahman, Zainal Ariff Abdul; Ismail, Siti Mazlipah; Abraham, Mannil Thomas; Tay, Keng Kiong; Mustafa, Wan Mahadzir Wan; Cheong, Sok Ching; Zain, Rosnah Binti

2015-01-01

BACKGROUND: Collagen Triple Helix Repeat Containing 1 (CTHRC1) is a protein often found to be over-expressed in various types of human cancers. However, correlation between CTHRC1 expression level with clinico-pathological characteristics and prognosis in oral cancer remains unclear. Therefore, this study aimed to determine mRNA and protein expression of CTHRC1 in oral squamous cell carcinoma (OSCC) and to evaluate the clinical and prognostic impact of CTHRC1 in OSCC. METHODS: In this study, mRNA and protein expression of CTHRC1 in OSCCs were determined by quantitative PCR and immunohistochemistry, respectively. The association between CTHRC1 and clinico-pathological parameters were evaluated by univariate and multivariate binary logistic regression analyses. Correlation between CTHRC1 protein expressions with survival were analysed using Kaplan-Meier and Cox regression models. RESULTS: Current study demonstrated CTHRC1 was significantly overexpressed at the mRNA level in OSCC. Univariate analyses indicated a high-expression of CTHRC1 that was significantly associated with advanced stage pTNM staging, tumour size ≥ 4 cm and positive lymph node metastasis (LNM). However, only positive LNM remained significant after adjusting with other confounder factors in multivariate logistic regression analyses. Kaplan-Meier survival analyses and Cox model demonstrated that patients with high-expression of CTHRC1 protein were associated with poor prognosis and is an independent prognostic factor in OSCC. CONCLUSION: This study indicated that over-expression of CTHRC1 potentially as an independent predictor for positive LNM and poor prognosis in OSCC. PMID:26664254

Triggers, risk factors and clinico-pathological features of urticaria in dogs - a prospective observational study of 24 cases.

PubMed

Rostaher, Ana; Hofer-Inteeworn, Natalie; Kümmerle-Fraune, Claudia; Fischer, Nina Maria; Favrot, Claude

2017-02-01

Urticaria and anaphylaxis are frequently encountered in veterinary practice, but little is known about the causes and relative frequencies of these reactions. This study was designed to improve current knowledge on the triggers, risk factors and clinico-pathological features of urticaria. Twenty four dogs with signs of urticaria with or without anaphylaxis. The study included dogs with cutaneous immediate-type hypersensitivity reactions. The cases were grouped by clinical severity into either an urticaria or an anaphylaxis group. All treatments and diagnostic tests (haematology, biochemical profile, allergy investigation) were recorded. A causality algorithm for urticaria and anaphylaxis (ALUA) was designed to determine the probability of the identified triggers and cofactors. Disease incidence, breed, age and gender predispositions were evaluated statistically. Sixteen of 24 urticaria cases were associated with anaphylaxis whilst 8 of 24 were confined to the skin. The annual hospital incidence was 0.12%. Females seemed to be over-represented (2.4:1) and most of the dog breeds were pure breed (22 of 24), with Rhodesian ridgeback, boxer, beagle, Jack Russell terrier, French bulldog and Vizslas over-represented. In addition to skin lesions, the most frequently and severely affected organ systems were the gastrointestinal and cardiovascular systems. The predominant blood abnormalities were elevated lipase and alanine aminotransferase values. Insects, food and drugs were the most commonly identified triggers. To the best of our knowledge, this is the first study describing the trigger factors and clinico-pathological features of dogs with urticaria in veterinary medicine. Insects, food and drugs were the most frequently detected triggers. © 2016 ESVD and ACVD.

Orbital Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease: An Analysis of Vascular Growth Factors with Clinical Correlation.

PubMed

Wong, Lindsay L; Lee, Nahyoung Grace; Amarnani, Dhanesh; Choi, Catherine J; Bielenberg, Diane R; Freitag, Suzanne K; D'Amore, Patricia A; Kim, Leo A

2016-09-01

The human orbit is an environment that is vulnerable to inflammation and edema in the setting of autoimmune thyroid disease. Our study investigated the tenet that orbital adipose tissue lacks lymphatic vessels and analyzed the clinicopathologic differences between patients with acute and chronic thyroid eye disease (TED). The underlying molecular mediators of blood and lymphatic vessel formation within the orbital fat also were evaluated. Retrospective cohort study. The study included fat specimens from 26 orbits of 15 patients with TED undergoing orbital decompression. Orbital fat specimens from patients without TED as well as cadaveric orbital fat served as controls. Tissue specimens were processed as formalin-fixed, paraffin-embedded sections or frozen cryosections for immunohistochemistry. Total RNA was extracted and analyzed via quantitative (real-time) reverse-transcription polymerase chain reaction. Clinicopathologic correlation was made by determining the clinical activity score (CAS) of each patient with TED. Samples were examined for vascular and lymphatic markers including podoplanin, lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and cluster of differentiation 31 (CD31) by immunohistochemistry, as well as for mRNA levels of vascular endothelial growth factor (VEGF), VEGF receptors, semaphorin 3F, neuropilin 1, neuropilin 2, podoplanin, and LYVE-1 by quantitative (real-time) reverse-transcription polymerase chain reaction. Clinicopathologic correlation revealed increased staining of CD31-positive blood vessels in patients with acute TED with a CAS more than 4, as well as rare staining of podoplanin-positive lymphatic vessels within acutely inflamed orbital fat tissue. Additionally, quantitative (real-time) reverse-transcription polymerase chain reaction analysis demonstrated increased expression of VEGF receptor (VEGFR) 2 as well as VEGF signaling molecules VEGF-A, VEGF-C, and VEGF-D. In acute TED, compared with chronic TED and control orbital fat, there is increased blood vessel density, suggesting neovascularization and rare lymphatic vessels suggestive of limited lymphangiogenesis. This proangiogenic and prolymphangiogenic microenvironment is likely the result of the increased expression of VEGFR-2, VEGF-A, VEGF-C, and VEGF-D. These findings imply that orbital edema in acute TED may be mediated, in part, by both the formation of new, immature blood vessels and the formation of lymphatic capillaries that are functionally incapable of draining interstitial fluid. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

First report on molecular breast cancer subtypes and their clinico-pathological characteristics in Eastern Morocco: series of 2260 cases.

PubMed

Elidrissi Errahhali, Manal; Elidrissi Errahhali, Mounia; Ouarzane, Meryem; El Harroudi, Tijani; Afqir, Said; Bellaoui, Mohammed

2017-01-09

Breast cancer is the most frequent malignancy among women in Eastern Morocco. In this paper, we provide the first report on molecular breast cancer subtypes in this region. This is the largest population-based study on breast cancer among Moroccan women. We analyzed 2260 breast cancer cases diagnosed at the Hassan II Regional Oncology Center between October 2005 and December 2012. Clinico-pathological and therapeutic features were studied. Molecular subtypes were determined and their associations with the clinico-pathological characteristics of the tumors were examined. The mean age at diagnosis was 48.7 years ±11.4. Invasive ductal carcinoma was the predominant histological type (77.1%), followed by lobular invasive carcinoma (15.3%). The mean size of breast tumors was 3.5 cm ± 1.96, and 84% of our patients are diagnosed with tumors of more than 2 cm. Histological grade II tumors were the most frequent (70.4%), followed by advanced histological grade (18%). Lymph node positive tumors were observed in 64.8% of cases and 29.3% of patients had distant metastasis. Most tumors were hormone receptor-positive (73%) and 28.6% were HER2 positive. 86.1% of patients with hormone receptor-positive breast cancer were given hormone therapy, while 68.9% of patients with HER2+ breast cancer received targeted therapy with Herceptin. Luminal A was the commonest molecular subtype, followed by Luminal B, Triple Negative and HER2. The highest prevalence of premenopausal patients was observed in Triple Negative subtype (72.2%), followed by HER2 (64.1%), Luminal B (62.2%), and Luminal A (55.1%). Luminal B subtype had a poorer prognosis than Luminal A. Compared with Triple Negative, HER2 subtype tend to spread more aggressively and is associated with poorer prognosis. Unlike Western countries, breast cancer occurs at an earlier age and is diagnosed at a more advanced stage in Eastern Morocco. In this region, hormone receptor-positive tumors are predominant and so the majority of breast cancer patients should benefit from hormone therapy. HER2 subtype presents an aggressive tendency, suggesting the importance of anti-HER2 therapy. This study will contribute in developing appropriate screening and cancer management strategies in Eastern Morocco.

Osteopontin expression and clinicopathologic correlation of oral hyperplastic reactive lesions: An institutional 6-year retrospective study

PubMed Central

Narwal, Anjali; Bala, Shashi

2017-01-01

Background and Objective: Reactive proliferations of oral cavity comprise pyogenic granuloma (PG), fibrous hyperplasia (FH), peripheral ossifying fibroma (POF), and peripheral giant-cell granuloma (PGCG). They often pose diagnostic challenges due to their overlapping clinical and histopathological features. This study was conducted to determine the frequency and clinicopathological correlation of reactive hyperplastic lesions in the oral cavity reported in our institute and compared it with other previous studies. Further evaluation of osteopontin (OPN) expression in normal gingival tissue and different types of focal reactive lesions was also done. Materials and Methods: Data of all reactive hyperplasias were retrieved, reviewed, and analyzed for age, gender, clinical presentation, and site of location. Presence and distribution of OPN were assessed using immunohistochemistry in these reactive lesions. Results: Two hundred and forty-eight reactive lesions were comprised of FH (38%), PG (23%), POF (13%), and PGCG (7%). FH was more common in males (55%) whereas other reactive lesions were more in females (68%–73%). The most frequently involved site was gingiva (59%), and most common clinical presentation was sessile growth on gingiva. OPN expression was minimal in normal gingiva. Few cases of FH, PG, and all cases of POF showed positivity for OPN in inflammatory cells, stromal cells, extracellular matrix, and in calcifications. Conclusion: Reactive hyperplastic lesions of oral cavity are mucosal responses to chronic low-grade irritation caused by plaque, calculus, and any other irritant. It is helpful to know their frequency and presentation as their early identification enables accurate patient evaluation and management. PMID:29391712

A Clinicopathological Investigation of White Matter Hyperintensities and Alzheimer's Disease Neuropathology.

PubMed

Alosco, Michael L; Sugarman, Michael A; Besser, Lilah M; Tripodis, Yorghos; Martin, Brett; Palmisano, Joseph N; Kowall, Neil W; Au, Rhoda; Mez, Jesse; DeCarli, Charles; Stein, Thor D; McKee, Ann C; Killiany, Ronald J; Stern, Robert A

2018-01-01

White matter hyperintensities (WMH) on magnetic resonance imaging (MRI) have been postulated to be a core feature of Alzheimer's disease. Clinicopathological studies are needed to elucidate and confirm this possibility. This study examined: 1) the association between antemortem WMH and autopsy-confirmed Alzheimer's disease neuropathology (ADNP), 2) the relationship between WMH and dementia in participants with ADNP, and 3) the relationships among cerebrovascular disease, WMH, and ADNP. The sample included 82 participants from the National Alzheimer's Coordinating Center's Data Sets who had quantitated volume of WMH from antemortem FLAIR MRI and available neuropathological data. The Clinical Dementia Rating (CDR) scale (from MRI visit) operationalized dementia status. ADNP+ was defined by moderate to frequent neuritic plaques and Braak stage III-VI at autopsy. Cerebrovascular disease neuropathology included infarcts or lacunes, microinfarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy. 60/82 participants were ADNP+. Greater volume of WMH predicted increased odds for ADNP (p = 0.037). In ADNP+ participants, greater WMH corresponded with increased odds for dementia (CDR≥1; p = 0.038). WMH predicted cerebral amyloid angiopathy, microinfarcts, infarcts, and lacunes (ps < 0.04). ADNP+ participants were more likely to have moderate-severe arteriolosclerosis and cerebral amyloid angiopathy compared to ADNP-participants (ps < 0.04). This study found a direct association between total volume of WMH and increased odds for having ADNP. In patients with Alzheimer's disease, FLAIR MRI WMH may be able to provide key insight into disease severity and progression. The association between WMH and ADNP may be explained by underlying cerebrovascular disease.

Osteoid producing primary lesion at morphologic and biologic interface.

PubMed

Sarkar, Reena Radhikaprasad

2015-01-01

Fibroosseous gnathic lesions comprise a wide spectrum of diseases. Many of the entities have overlapping features. A pediatric case is encountered with a complex clinicopathologic profile. Although radiographically the lesion appears benign but on histopathological examination it possesses features of osteoid producing aggressive neoplasm. This paper highlights the unusual histologic features existing within the spectrum of fibroosseous lesions and discusses relevant clinicopathologic correlations.

Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients' survival.

PubMed

Theocharis, Stamatios; Giaginis, Constantinos; Alexandrou, Paraskevi; Rodriguez, Jose; Tasoulas, Jason; Danas, Eugene; Patsouris, Efstratios; Klijanienko, Jerzy

2016-03-01

Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). CB1R and CB2R expression was assessed immunohistochemically on 28 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics and overall and disease-free patients' survival. CB1R, CB2R, and concomitant CB1R/CB2R expression was significantly increased in older compared to younger mobile tongue SCC patients (p = 0.0243, p = 0.0079, and p = 0.0366, respectively). Enhanced CB2R and concomitant CB1R/CB2R expression was significantly more frequently observed in female compared to male mobile tongue SCC patients (p = 0.0025 and p = 0.0016, respectively). Elevated CB2R expression was significantly more frequently observed in mobile tongue SCC patients presenting well-defined tumor shape compared to those with diffuse (p = 0.0430). Mobile tongue SCC patients presenting enhanced CB1R, CB2R, or concomitant CB1R/CB2R expression showed significantly longer overall (log-rank test, p = 0.004, p = 0.011, p = 0.018, respectively) and disease-free (log-rank test, p = 0.003, p = 0.007, p = 0.027, respectively) survival times compared to those with low expression. In multivariate analysis, CB1R was identified as an independent prognostic factor for disease-free patients' survival (Cox-regression analysis, p = 0.032). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.

Lung cancer in patients younger than 40 years in a multiracial Asian country.

PubMed

Liam, C K; Lim, K H; Wong, C M

2000-12-01

This study aimed to determine whether the clinicopathological features of lung cancer in patients younger than 40 years differ from that of older patients in an Asian country. We undertook a review of the clinicopathological data of all patients with confirmed primary lung cancer at the Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia, from October 1991 to September 1999. Of the 580 patients with lung cancer, 36 (6.2%; 23 males, 13 females) were 21-39 years old at diagnosis. The percentage of people who had never smoked was higher among the younger patients (58.3% vs 19.1%, P < 0.001). Although adenocarcinoma was the most common cell type in both groups, its incidence was higher in the younger patients (24/36 (66.7%) vs 228/544 (41.9%), P = 0.007). The mean World Health Organization performance status at presentation was worse in the younger patients (2.4 vs 2, P = 0.007). In the case of non-small cell lung cancer, all the younger patients presented with either stage IIIb or metastatic disease compared to 77.2% of the older patients (P < 0.001). Younger lung cancer patients were more likely than older patients to have never smoked, to have adenocarcinoma, and to present with poorer performance status and with more advanced-stage non-small cell lung cancer.

High prevalence of luminal B breast cancer intrinsic subtype in Colombian women

PubMed Central

Serrano-Gomez, Silvia Juliana; Sanabria-Salas, Maria Carolina; Hernández-Suarez, Gustavo; García, Oscar; Silva, Camilo; Romero, Alejandro; Mejía, Juan Carlos; Miele, Lucio; Fejerman, Laura; Zabaleta, Jovanny

2016-01-01

Breast cancer is the most frequent malignancy in women worldwide. Distinct intrinsic subtypes of breast cancer have different prognoses, and their relative prevalence varies significantly among ethnic groups. Little is known about the prevalence of breast cancer intrinsic subtypes and their association with clinicopathological data and genetic ancestry in Latin Americans. Immunohistochemistry surrogates from the 2013 St. Gallen International Expert Consensus were used to classify breast cancers in 301 patients from Colombia into intrinsic subtypes. We analyzed the distribution of subtypes by clinicopathological variables. Genetic ancestry was estimated from a panel of 80 ancestry informative markers. Luminal B breast cancer subtype was the most prevalent in our population (37.2%) followed by luminal A (26.3%), non-basal triple negative (NBTN) (11.6%), basal like (9%), human epidermal growth factor receptor 2 (HER2) enriched (8.6%) and unknown (7.3%). We found statistical significant differences in distribution between Colombian region (P = 0.007), age at diagnosis (P = 0.0139), grade (P < 0.001) and recurrence (P < 0.001) according to intrinsic subtype. Patients diagnosed with HER2-enriched, basal-like and NBTN breast cancer had the highest African ancestry. Future studies analyzing the molecular profiles of breast cancer in Colombian women will help us understand the molecular basis of this subtype distribution and compare the molecular characteristics of the different intrinsic subtypes in Colombian patients. PMID:27207651

Lung cancer in younger patients.

PubMed

Abbasowa, Leda; Madsen, Poul Henning

2016-07-01

Lung cancer remains a leading cause of cancer-related death. The incidence increases with age and the occurrence in young patients is relatively low. The clinicopathological features of lung cancer in younger patients have not been fully explored previously. To assess the age differences in the clinical characteristics of lung cancer, we conducted a retrospective analysis comparing young patients ≤ 65 years of age with an elderly group > 65 years of age. Among 1,232 patients evaluated due to suspicion of lung cancer in our fast-track setting from January-December 2013, 312 newly diagnosed lung cancer patients were included. Patients ≤ 65 years had a significantly higher representation of females (p = 0.0021), more frequent familial cancer aggregation (p = 0.028) and a lower incidence of squamous cell carcinoma (p = 0.0133). When excluding pure carcinoid tumours, a significantly higher proportion of the younger patients presented with advanced stage disease (p = 0.0392). Combined modality therapy was more common in younger patients (p = 0.0009), while chemotherapy appeared less prevalent among the elderly (p = 0.0015). Lung cancer in younger patients comprises a distinct clinicopathological entity with more frequent advanced stage disease and a significantly greater proportion with a family history of cancer. Implementing genetic background assessments and considering lung cancer as a possible diagnosis in younger, symptomatic patients, is of paramount importance. none. The study was approved by the -Danish Data Protection Agency.

Comparison of non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer.

PubMed

Feng, Hao; Lu, Ai-Guo; Zhao, Xue-Wei; Han, Ding-Pei; Zhao, Jing-Kun; Shi, Lei; Schiergens, Tobias S; Lee, Serene M L; Zhang, Wen-Peng; Thasler, Wolfgang E

2015-06-21

To compare the clinicopathological features of patients with non-schistosomal rectosigmoid cancer and schistosomal rectosigmoid cancer. All the patients with rectosigmoid carcinoma who underwent laparoscopic radical surgical resection in the Shanghai Minimally Invasive Surgical Center at Ruijin Hospital affiliated to Shanghai Jiao-Tong University between October 2009 and October 2013 were included in this study. Twenty-six cases of colonic schistosomiasis diagnosed through colonoscopy and pathological examinations were collected. Symptoms, endoscopic findings and clinicopathological characteristics were evaluated retrospectively. There were no significant differences between patients with and without schistosomiasis in gender, age, CEA, CA19-9, preoperative biopsy findings or postoperative pathology. Patients with rectosigmoid schistosomiasis had a significantly higher CA-125 level and a larger proportion of these patients were at an early tumor stage (P = 0.003). Various morphological characteristics of schistosomiasis combined with rectosigmoid cancer could be found by colonoscopic examination: 46% were fungating mass polyps, 23% were congestive and ulcerative polyps, 23% were cauliflower-like masses, 8% were annular masses. Only 27% of the patients were diagnosed with rectal carcinoma preoperatively after the biopsy. Computed tomography (CT) scans showed thickened intestinal walls combined with linear and tram-track calcifications in 26 patients. Rectosigmoid carcinoma combined with schistosomiasis is associated with higher CA-125 values and early tumor stages. CA-125 and CT scans have a reasonable sensitivity for the accurate diagnosis.

Increasing incidence of adenocarcinoma lung in India: Following the global trend?

PubMed

Mohan, A; Latifi, A N; Guleria, R

2016-01-01

Lung cancer is one of the most common malignant neoplasms worldwide and accounts for more deaths than any other cancer. The clinicopathological profile of lung cancer has shown marked regional and geographical variation. We aimed to compare the demographic and pathological profile of lung cancer patients from North India with other Indian and International series. A retrospective study over a period of 5 years from January 2008 to May 2013 was conducted in the Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, New Delhi. A total of 397 newly diagnosed patients with lung cancer from January 2008 to May 2013 were included in the study. The clinical, demographic, and pathological features were reviewed and compared with other major National and International reports. Data were entered and analyzed using SPSS software (SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc. A total of 397 patients (86% men, mean age 57.8 years) were studied. The ratio of men to women was 7.4. Majority of patients (78.3%) were current/previous smokers. Small cell carcinoma was diagnosed in 14.6% (58) of patients while 85.4% (339) had nonsmall cell lung carcinoma (NSCLC). Within NSCLC, the most common histology types were squamous cell carcinoma (30%), followed closely by adenocarcinoma (ADC) (28.3%) and large cell carcinoma (1.7%). Majority (87%) of the patient were staged III and IV. About 30.1% patients received anti-tubercular treatment during the current episode before a diagnosis of lung cancer was made. The clinicopathological profile of lung cancer has undergone noticeable changes over the last four decades, especially in the increase in ADC incidence and their frequent presence in smokers. Lung cancer is often mistreated as tuberculosis in the Indian subcontinent and hence continues to be diagnosed late.

A multigene prognostic assay for selection of adjuvant chemotherapy in patients with T3, stage II colon cancer: impact on quality-adjusted life expectancy and costs.

PubMed

Hornberger, John; Lyman, Gary H; Chien, Rebecca; Meropol, Neal J

2012-12-01

Uncertainty exists regarding appropriate and affordable use of adjuvant chemotherapy in stage II colon cancer (T3, proficient DNA mismatch repair). This study aimed to estimate the effectiveness and costs from a US societal perspective of a multigene recurrence score (RS) assay for patients recently diagnosed with stage II colon cancer (T3, proficient DNA mismatch repair) eligible for adjuvant chemotherapy. RS was compared with guideline-recommended clinicopathological factors (tumor stage, lymph nodes examined, tumor grade, and lymphovascular invasion) by using a state-transition (Markov) lifetime model. Data were obtained from published literature, a randomized controlled trial (QUick And Simple And Reliable) of adjuvant chemotherapy, and rates of chemotherapy use from the National Cooperative Cancer Network Colon/Rectum Cancer Outcomes study. Life-years, quality-adjusted life expectancy, and lifetime costs were examined. The RS is projected to reduce adjuvant chemotherapy use by 17% compared with current treatment patterns and to increase quality-adjusted life expectancy by an average of 0.035 years. Direct medical costs are expected to decrease by an average of $2971 per patient. The assay was cost saving for all subgroups of patients stratified by clinicopathologic factors. The most influential variables affecting treatment decisions were projected years of life remaining, recurrence score, and patients' disutilities associated with adjuvant chemotherapy. Use of the multigene RS to assess recurrence risk after surgery in stage II colon cancer (T3, proficient DNA mismatch repair) may reduce the use of adjuvant chemotherapy without decreasing quality-adjusted life expectancy and be cost saving from a societal perspective. These findings need to be validated in additional cohorts, including studies of clinical practice as assay use diffuses into nonacademic settings. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Prognostic Value and Clinicopathological Significance of p-stat3 Among Gastric Carcinoma Patients: A Systematic Review and Meta-Analysis.

PubMed

Ji, Kun; Zhang, Liyan; Zhang, Mingxuan; Chu, Qi; Li, Xin; Wang, Wei

2016-02-01

The overexpression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) was detected in a variety of human tumors. The published studies on p-stat3 expression among gastric carcinoma patients remain controversial.In order to clarify the prognosis value of p-stat3 with overall survival and its association with clinicopathological characteristics in gastric carcinoma, we performed a systematic review and meta-analysis.Eligible studies were retrieved by searching PubMed, Embase, Cochrane library, and Chinese biomedical literature service system databases.Studies described the association between p-stat3 expression and clinicopathological characteristics and overall survival in gastric carcinoma patients; p-stat3 expression was detected by immunohistochemistry (IHC).Odds ratio (OR) and hazard ratio (HR) were considered as a measure of evaluating the association in meta-analysis; I was used to assess the heterogeneity across studies; publication bias was assessed with funnel plot, Egger test, and Begg test.Twenty-three studies including 2872 patients which evaluated the p-stat3 expression by IHC in gastric carcinoma were included. The pooled HR (HR = 2.02, 95% CI: 1.49-2.73, P < 0.00001) indicated that the increased p-stat3 expression was significantly associated with poor overall survival. In addition, when we investigated the association between p-stat3 overexpression and clinicopathological characteristics of gastric carcinoma, we found that the increased p-stat3 expression was significantly associated with tumor differentiation (poorly vs well-moderately: OR = 3.70, 95% CI: 1.98-6.93, P < 0.0001) and lymph node metastasis (present vs absent: OR = 2.40, 95% CI: 1.28-4.50, P = 0.007).The different type of primary antibody was used; the assessment methods of p-stat3 positive expression were defined differently; the locations of p-stat3 expression were different; the method of extrapolating HR from Kaplan-Meier survival curves did seem to be less reliable than when HR was extracted directly from literatures; sample sizes, the age of patients, and the follow-up durations are different.In conclusion, our meta-analysis indicates that the increased p-stat3 expression may be not only predict poor prognosis, but also be associated with worse tumor differentiation and lymph node metastasis in patients with gastric carcinoma.

Small cell carcinomas of the gastrointestinal tract: clinicopathological features and treatment approach.

PubMed

Brenner, Baruch; Tang, Laura H; Shia, Jinruh; Klimstra, David S; Kelsen, David P

2007-02-01

Small cell undifferentiated carcinoma (SmCC) of the gastrointestinal tract (GIT) is a rare and highly aggressive malignancy. To date, fewer than 1,000 cases have been reported, with an estimated prevalence of 0.1% to 1% of all gastrointestinal (GI) tumors. Data on the disease are scarce due to its rarity and the fact that most authors have focused on one site within the GIT. In light of the limited data and its perceived similarity to SmCC of the lung, the disease has usually been treated as the latter. Nevertheless, recent clinicopathologic and molecular data imply several differences between the two entities, questioning the extent to which extrapolations from one to the other can be made. We review the available data on GI SmCC with emphasis on outlining its clinicopathologic features and the recommended treatment approach.

Oral lichen planus to oral lichenoid lesions: Evolution or revolution

PubMed Central

Dudhia, Bhavin B; Dudhia, Sonal B; Patel, Purv S; Jani, Yesha V

2015-01-01

The diagnosis between different diseases may be impaired by clinical and histopathologic similarities, as observed in the oral lichen planus (OLP) and oral lichenoid lesion (OLL). Inspite of similar clinicopathological features; etiology, diagnosis and prognosis differ which mandates separation of OLL from OLP. Hence, it is essential for the oral physician and oral pathologist to be familiarized with the individual variations among clinicopathological features of OLP and OLL as well as to obtain a thorough history and perform a complete mucocutaneous examination in addition to specific diagnostic testing. The difficulties faced to establish the diagnosis between these two pathologies are widely investigated in the literature with a lack of definite conclusion. This review is an attempt to throw some light on these clinicopathologic entities with the aim to resolve the diagnostic dilemma. PMID:26980966

Acinar Cell Carcinoma of the Pancreas: Overview of Clinicopathologic Features and Insights into the Molecular Pathology.

PubMed

La Rosa, Stefano; Sessa, Fausto; Capella, Carlo

2015-01-01

Acinar cell carcinomas (ACCs) of the pancreas are rare pancreatic neoplasms accounting for about 1-2% of pancreatic tumors in adults and about 15% in pediatric subjects. They show different clinical symptoms at presentation, different morphological features, different outcomes, and different molecular alterations. This heterogeneous clinicopathological spectrum may give rise to difficulties in the clinical and pathological diagnosis with consequential therapeutic and prognostic implications. The molecular mechanisms involved in the onset and progression of ACCs are still not completely understood, although in recent years, several attempts have been made to clarify the molecular mechanisms involved in ACC biology. In this paper, we will review the main clinicopathological and molecular features of pancreatic ACCs of both adult and pediatric subjects to give the reader a comprehensive overview of this rare tumor type.

ESR1 gene amplification in endometrial carcinomas: a clinicopathological analysis.

PubMed

Rahman, Mohammed Tanjimur; Nakayama, Kentaro; Rahman, Munmun; Ishikawa, Masako; Katagiri, Hiroshi; Katagiri, Atsuko; Ishibashi, Tomoka; Sato, Emi; Iida, Kouji; Ishikawa, Noriyuki; Nakayama, Naomi; Miyazaki, Kohji

2013-09-01

This study investigated the clinicopathological significance of estrogen receptor 1 (ESR1) gene amplification and its relationship to phosphatase and tensin homolog (PTEN), human epidermal growth factor receptor 2 (HER2), MutL homolog 1 (MLH1), p53, and AT rich interactive domain 1A (ARID1A) expression in endometrial carcinomas. ESR1 amplification and expression were assessed by fluorescence in situ hybridization and immunohistochemistry. Clinical data were collected by retrospective chart review. ESR1 amplification was identified in 13 out of 111 (11.7%) endometrial carcinomas. No significant association was observed between ESR1 amplification and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.17), histological grade (p=0.35), lymph node metastasis (p=0.51), or deep myometrial invasion (p=0.46). ESR1 amplification was independent of PTEN, p53, HER2, MLH1, and ARID1A protein expression. Patients without estrogen receptor (ER) or progesterone receptor (PR) expression had shorter progression-free and overall survival than those with ER or PR expression (p<0.01). ESR1 amplification is independent of known clinicopathological factors related to poor prognosis and PTEN, p53, HER2, MLH1, and ARID1A protein expression, suggesting ESR1 amplification may be an early event in endometrial carcinoma development.

Clinicopathologic Characteristics and Treatment Outcomes of Penile Cancer

PubMed Central

Nam, Jong Kil; Lee, Dong Hoon; Park, Sung Woo; Kam, Sung Chul; Lee, Ki Soo; Kim, Tae Hyo; Kim, Taek Sang; Oh, Cheol Kyu; Park, Hyun Jun

2017-01-01

Purpose The aim of this study was to assess the clinicopathologic characteristics of penile cancer, including patterns of therapy, oncologic results, and survival. Materials and Methods Between January 2005 and July 2015, 71 patients at 6 institutions who had undergone penectomy or penile biopsy were enrolled. Their medical records were reviewed to identify the mode of therapy, pathology reports, and cancer-specific survival (CSS) rate. Results Clinicopathologic and outcome information was available for 52 male patients (mean age, 64.3 years; mean follow-up, 61.4 months). At presentation, 17 patients were node-positive, and 4 had metastatic disease. Management was partial penectomy in 34 patients, total penectomy in 12 patients, and chemotherapy or radiotherapy in 6 patients. The pathology reports were squamous cell carcinoma in 50 patients and other types of carcinoma in the remaining 2 patients. Kaplan-Meier survival analysis showed a 5-year CSS rate of 84.0%. In univariate and multivariate analyses, the American Joint Committee on Cancer (AJCC) stage and pathologic grade were associated with survival. Conclusions Partial penectomy was the most common treatment of penile lesions. The oncologic outcomes were good, with a 5-year CSS of 84.0%. The AJCC stage and pathologic grade were independent prognostic factors for survival. PMID:28459145

Central nervous system capillary haemangioblastoma: the pathologist's viewpoint

PubMed Central

Hussein, Mahmoud R

2007-01-01

Summary Haemangioblastomas are rare neoplasms of uncertain histogenesis. They represent 1.5–2.5% of intracranial tumours. While the cerebellum is by far the most frequent site, these lesions also tend to occur in the medulla and spinal cord. Most haemangioblastomas are sporadic but up to one quarter are associated with Von Hippel–Lindau disease (VHL). Although a fairly good number of haemangioblastomas were reported, a lack of side-by-side analysis of these reports has resulted in tentative conclusions that merely offer a first glimpse at their clinicopathologic diversity and histogenesis. To remedy this issue, this study presents a literature review concerning these lesions. Medline literature including both relevant monographs and clinicopathological case series. Haemangioblastomas occur either as a part of VHL disease (25–30%, inherited mutation of VHL gene on 3p25–26 chromosome) or as sporadic tumours (often with somatic mutation of VHL gene). They have diverse clinicopathologic presentations with cerebellar lesions having a better prognosis than their brainstem counterparts. Immunostaining is important for separation of haemangioblastomas from other tumours with similar histology. The rich vascularity of haemangioblastomas is due to overexpression of vascular endothelial growth factors. Moreover, ‘stromal’ cells represent the neoplastic cells of haemangioblastomas and are capable of forming blood islands with extramedullary haematopoiesis. PMID:17877533

Subependymomas: a clinicopathological study of 6 symptomatic cases.

PubMed

Limaïem, F; Bellil, S B H; Bellil, K; Chelly, I; Jemel, H; Haouet, S; Khaldi, M; Zitouna, M; Kchir, N

2008-10-01

Subependymomas are rare, slow-growing, ependymal neoplasms that commonly occur in the fourth or lateral ventricles. A retrospective study of 6 histologically proven subependymomas was undertaken to analyse their clinicopathological characteristics. There were five male and one female patients ranging in age from 11 to 50 years (mean 35.8 years). All patients were symptomatic at diagnosis. The most common clinical presentations included headache (n=6) and vomiting (n=3). Tumours were located in the lateral ventricle in five cases and in the fourth ventricle in one case. Magnetic resonance imaging detected obstructive hydrocephalus in all cases. Five patients underwent gross total resection and one patient had subtotal excision of the tumour. Histologically, all tumours were characterised by clustering of isomorphic cells arranged against a fibrillary background. Focal cystic degeneration was seen in 5 tumours. During the follow-up period, which ranged between 2 months and 10 years, all patients were symptom-free with no evidence of recurrence.

[Dandy-Walker complex: a clinicopathologic study of 9 cases].

PubMed

Zhang, Xiao-bo; Gu, Yi-qun; Sun, Xiao-fei; Wang, Ying-nan; Wang, Ai-chun

2013-12-01

To investigate the etiology, pathogenesis, clinicopathologic characteristics, clinical prognosis and treatment of Dandy-Walker syndrome. Nine cases of Dandy-Walker syndrome were included in the study. The autopsy findings and clinical history were evaluated along with review of the literature. The causes, pathogenetic mechanism, pathologic features and prognosis of Dandy-Walker syndrome were analyzed. Among 9 Dandy-Walker syndrome cases, six patients presented with variants of Dandy-Walker complex and 3 cases had classic Dandy-Walker malformation. In addition, 4 patients presented with combined lateral ventricle expansion and multiple malformations were seen in 7 cases. Combined umbilical cord abnormality was noted in 4 patients with variant of Dandy-Walker complex and combined placental abnormality was seen in one classic Dandy-Walker syndrome. Dandy-Walker syndrome is a rare disease. In addition to complex pathogenesis with possible genetic and environmental antigenic etiologies, placental and umbilical cord abnormality may be also related to its development.

Oncogenic osteomalacia: a clinicopathologic study of 17 bone lesions.

PubMed Central

Park, Y. K.; Unni, K. K.; Beabout, J. W.; Hodgson, S. F.

1994-01-01

Oncogenic osteomalacia is an unusual and rare clinicopathologic syndrome characterized by mesenchymal tumors that apparently produce osteomalacia and biochemical abnormalities consisting of hypophosphatemia, normocalcemia, and increased levels of alkaline phosphatase. We collected from the Mayo Clinic files and from our consultation files the records for 17 cases of osteomalacia associated with bone lesions. There were five cases of fibrous dysplasia, three of hemangiopericytoma, and two of phosphaturic mesenchymal tumor. There was one case each of osteosarcoma, chondroblastoma, chondromyxoid fibroma, malignant fibrous histiocytoma, giant cell tumor, metaphyseal fibrous defect, and hemangioma. In this study we can figure out that the most common characteristic histologic features of our cases were hemangiopericytomatous vascular proliferation, fine lace-like stromal calcification, and stromal giant cells. In most of the cases, the clinical and biochemical symptoms and signs resolved soon after complete resection of the lesion. When the lesion recurred or metastasized, the symptoms and signs also recurred. PMID:7848576

Prognostic Significance of BMI-1 But Not MEL-18 Expression in Pulmonary Squamous Cell Carcinoma.

PubMed

Abe, Sosei; Yamashita, Shin-Ichi; Miyahara, S O; Wakahara, Junichi; Yamamoto, Leona; Mori, Ryo; Imamura, Naoko; Yoshida, Yasuhiro; Waseda, Ryuichi; Hiratsuka, Masafumi; Shiraishi, Takeshi; Nabeshima, Kazuki; Iwasaki, Akinori

2017-04-01

We investigated the possibility of BMI-1 and MEL-18 to predict survival in patients with pulmonary squamous cell carcinoma. One hundred and ninety-nine patients underwent surgery in our Institute between 1995 and 2005. We used immunohistochemical (IHC) analysis to determine the expressions of BMI-1 and MEL-18 and compared them with clinicopathological factors and survival. Forty-one of 199 cases (21%) were BMI-1-positive. No correlation was found between BMI-1 and MEL-18 expression by IHC and clinicopathological factors. Five-year overall survival in the BMI-1-positive group (66.8%), but not MEL-18, was significantly better than that in the negative group (45.5%, p=0.04). In multivariate analysis, positive BMI-1 was a better prognostic factor of overall survival (hazard ratio (HR)=0.561, 95% confidence interval (CI)=0.271-1.16, p=0.12). BMI-1 expression, but not MEL-18, is associated with a favorable prognosis and is a possible prognostic factor of pulmonary squamous cell carcinoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Variations in clinicopathologic characteristics of thyroid cancer among racial ethnic groups: analysis of a large public city hospital and the SEER database.

PubMed

Moo-Young, Tricia A; Panergo, Jessel; Wang, Chih E; Patel, Subhash; Duh, Hong Yan; Winchester, David J; Prinz, Richard A; Fogelfeld, Leon

2013-11-01

Clinicopathologic variables influence the treatment and prognosis of patients with thyroid cancer. A retrospective analysis of public hospital thyroid cancer database and the Surveillance, Epidemiology and End Results 17 database was conducted. Demographic, clinical, and pathologic data were compared across ethnic groups. Within the public hospital database, Hispanics versus non-Hispanic whites were younger and had more lymph node involvement (34% vs 17%, P < .001). Median tumor size was not statistically different across ethnic groups. Similar findings were demonstrated within the Surveillance, Epidemiology and End Results database. African Americans aged <45 years had the largest tumors but were least likely to have lymph node involvement. Asians had the most stage IV disease despite having no differences in tumor size, lymph node involvement, and capsular invasion. There is considerable variability in the clinical presentation of thyroid cancer across ethnic groups. Such disparities persist within an equal-access health care system. These findings suggest that factors beyond socioeconomics may contribute to such differences. Copyright © 2013 Elsevier Inc. All rights reserved.

RASSF1A protein expression and correlation with clinicopathological parameters in renal cell carcinoma

PubMed Central

Tezval, Hossein; Merseburger, Axel S; Matuschek, Ira; Machtens, Stefan; Kuczyk, Markus A; Serth, Jürgen

2008-01-01

Background Epigenetic silencing of RAS association family 1A (RASSF1A) tumor suppressor gene occurs in various histological subtypes of renal cell carcinoma (RCC) but RASSF1A protein expression in clear cell RCC as well as a possible correlation with clinicopathological parameters of patients has not been analyzed at yet. Methods 318 primary clear cell carcinomas were analyzed using tissue microarray analysis and immunohistochemistry. Survival analysis was carried out for 187 patients considering a follow-up period of 2–240 month. Results Expression of RASSF1A was found to be significantly decreased in tumoral cells when compared to normal tubular epithelial cells. RASSF1A immunopositivity was significantly associated with pT stage, group stage and histological grade of tumors and showed a tendency for impaired survival in Kaplan-Meier analysis. Conclusion While most tumors demonstrate a loss of RASSF1A protein, a subset of tumors was identified to exhibit substantial RASSF1A protein expression and show increased tumor progression. Thus RCC tumorigenesis without depletion of RASSF1A may be associated with an adverse clinical outcome. PMID:18822131

[Renal cell carcinoma with t(6;11)(p21.2;q13)/MALAT1-TFEB fusion: a clinical and pathological analysis].

PubMed

Xia, Qiuyuan; Shi, Shanshan; Shen, Qin; Wei, Xue; Wang, Xuan; Ma, Henghui; Lu, Zhenfeng; Zhou, Xiaojun; Rao, Qiu

2015-12-01

To study the clinicopathologic features, immunophenotype, differential diagnosis and prognosis of renal cell carcinoma (RCC) associated with t(6;11)(p21.2;q13)/MALAT1-TFEB gene fusion. A total of 9 cases of such rare tumor were selected for clinicopathologic, immunohistochemical and molecular analysis, with review of literature. The age of the patients ranged from 21 to 42 years (mean=31.3 years). The patients included four men and five women. Histologically, 4 of the 9 cases studied showed classic morphologic features of TFEB RCC, with hyaline material, pigments and psammoma bodies frequently identified. The remaining 5 cases demonstrated uncommon morphology, mimicking perivascular epithelioid cell neoplasm, clear cell RCC, chromophobe RCC or papillary RCC. Immunohistochemical study showed that TFEB and vimentin were positive in all cases. Most of the tumors studied also expressed Ksp-cadherin, E-cadherin, CD117, HMB45, Melan A and Cathepsin K. CKpan showed immunostaining in only 1 case. The staining for TFE3, CD10 and CK7 were all negative. TFEB gene rearrangement was detected in all the 9 cases studied using fluorescence in-situ hybridization. MALAT1-TFEB fusion gene was identified in 2 cases by polymerase chain reaction and direct sequencing. TFEB RCC seemed to be an indolent tumor. During a mean follow-up of 31 months, none developed tumor recurrence, progression, or metastasis. TFEB fusion-associated RCC is a rare neoplasm, tends to occur in young age group and carries an indolent behavior. Diagnosis relies on clinicopathologic findings and immunohistochemical analysis. TFEB break-apart FISH assay is a reliable tool in confirming the diagnosis.

Clinicopathological parameters, recurrence, locoregional and distant metastasis in 115 T1-T2 oral squamous cell carcinoma patients

PubMed Central

2010-01-01

The incidence of oral squamous cell carcinoma remains high. Oral and oro-pharyngeal carcinomas are the sixth most common cancer in the world. Several clinicopathological parameters have been implicated in prognosis, recurrence and survival, following oral squamous cell carcinoma. In this retrospective analysis, clinicopathological parameters of 115 T1/T2 OSCC were studied and compared to recurrence and death from tumour-related causes. The study protocol was approved by the Joint UCL/UCLH committees of the ethics for human research. The patients' data was entered onto proformas, which were validated and checked by interval sampling. The fields included a range of clinical, operative and histopathological variables related to the status of the surgical margins. Data collection also included recurrence, cause of death, date of death and last clinic review. Causes of death were collated in 4 categories (1) death from locoregional spread, (2) death from distant metastasis, (3) death from bronchopulmonary pneumonia, and (4) death from any non-tumour event that lead to cardiorespiratory failure. The patients' population comprised 65 males and 50 females. Their mean age at the 1st diagnosis of OSCC was 61.7 years. Two-thirds of the patients were Caucasians. Primary sites were mainly identified in the tongue, floor of mouth (FOM), buccal mucosa and alveolus. Most of the identified OSCCs were low-risk (T1N0 and T2N0). All patients underwent primary resection ± neck dissection and reconstruction when necessary. Twenty-two patients needed adjuvant radiotherapy. Pathological analysis revealed that half of the patients had moderately differentiated OSCC. pTNM slightly differed from the cTNM and showed that 70.4% of the patients had low-risk OSCC. Tumour clearance was ultimately achieved in 107 patients. Follow-up resulted in a 3-year survival of 74.8% and a 5-year survival of 72.2%. Recurrence was identified in 23 males and 20 females. The mean age of 1st diagnosis of the recurrence group was 59.53 years. Most common oral sites included the lateral border of tongue and floor of mouth. Recurrence was associated with clinical N-stage disease. The surgical margins in this group was evaluated and found that 17 had non-cohesive invasion, 30 had dysplasia at margin, 21 had vascular invasion, 9 had nerve invasion and 3 had bony invasion. Severe dysplasia was present in 37 patients. Tumour clearance was achieved in only 8 patients. The mean depth of tumour invasion in the recurrence group was 7.6 mm. An interesting finding was that 5/11 patients who died of distant metastasis had their primary disease in the tongue. Nodal disease comparison showed that 8/10 patients who died of locoregional metastasis and 8/11 patients who died from distant metastasis had clinical nodal involvement. Comparing this to pathological nodal disease (pTNM) showed that 10/10 patients and 10/11 patients who died from locoregional and distant metastasis, respectively, had nodal disease. All patients who died from locoregional and distant metastasis were shown to have recurrence after the primary tumour resection. Squamous cell carcinoma of the oral cavity has a poor overall prognosis with a high tendency to recur at the primary site and extend to involve the cervical lymph nodes. Several clinicopathological parameters can be employed to assess outcome, recurrence and overall survival. PMID:20406474

Comparison of Perioperative Outcomes between Open, Laparoscopic, and Robotic Distal Pancreatectomy: an Analysis of 1815 Patients from the ACS-NSQIP Procedure-Targeted Pancreatectomy Database.

PubMed

Xourafas, Dimitrios; Ashley, Stanley W; Clancy, Thomas E

2017-09-01

Robotic surgery is gaining acceptance for distal pancreatectomy (DP). Nevertheless, no multi-institutional data exist to demonstrate the ideal clinical circumstances for use and the efficacy of the robot compared to the open or laparoscopic techniques, in terms of perioperative outcomes. The 2014 ACS-NSQIP procedure-targeted pancreatectomy data for patients undergoing DP were analyzed. Demographics and clinicopathological and perioperative variables were compared between the three approaches. Univariate and multivariable analyses were used to evaluate outcomes. One thousand eight hundred fifteen DPs comprised 921 open distal pancreatectomies (ODPs), 694 laparoscopic distal pancreatectomies (LDPs), and 200 robotic distal pancreatectomies (RDPs). The three groups were comparable with respect to demographics, ASA score, relevant comorbidities, and malignant histology subtype. Compared to the ODP group, patients undergoing RDP had lower T-stages of disease (P = 0.0192), longer operations (P = 0.0030), shorter hospital stays (P < 0.0001), and lower postoperative 30-day morbidity (P = 0.0476). Compared to the LDP group, RDPs were longer operations (P < 0.0001) but required fewer concomitant vascular resections (P = 0.0487) and conversions to open surgery (P = 0.0068). On multivariable analysis, neoadjuvant therapy (P = 0.0236), malignant histology (P = 0.0124), pancreatic reconstruction (P = 0.0006), and vascular resection (P = 0.0008) were the strongest predictors of performing an ODP. The open, laparoscopic, and robotic approaches to distal pancreatectomy offer particular advantages for well-selected patients and specific clinicopathological contexts; therefore, clearly demonstrating the most suitable use and superiority of one technique over another remains challenging.

Prognostic and clinicopathological significance of long noncoding RNA HOXA11-AS expression in human solid tumors: a meta-analysis.

PubMed

Mu, Shidai; Ai, Lisha; Fan, Fengjuan; Sun, Chunyan; Hu, Yu

2018-01-01

Recent studies have emphasized the important prognostic role of long noncoding RNAs (lncRNAs) in various types of cancers. Here we conducted a meta-analysis to investigate whether lncRNA HOXA11-AS can be served as a prognostic biomarker in human cancers. We systematically searched PubMed, Embase, ISI Web of Science, and SCOPUS for relevant studies, to investigate the prognostic significance of HOXA11-AS expression in cancer patients. Odds ratios (ORs) or hazards ratios (HRs) with corresponding 95% confidence intervals (CIs) are pooled to estimate the association between HOXA11-AS expression and clinicopathological parameters or survival of cancer patients. A total of eight eligible studies with 1320 cancer patients were enrolled in our meta-analysis. The results revealed that increased expression level of HOXA11-AS was significantly associated with clinicopathological parameters including more lymph node metastasis (OR = 2.06, 95% CI 1.31-3.25), advanced tumor stage (OR = 4.22, 95% CI 2.60-6.85), as well as poor tumor differentiation (OR = 2.49, 95 CI 1.47-4.20), but not correlated with age ( p  = 0.101) or gender ( p  = 0.845). In addition, cancer patients with high HOXA11-AS are prognosed to have shorter OS (pooled HR = 1.86, 95% CI 1.39-2.48) and PFS (pooled HR = 2.47, 95% CI 1.29-4.75). HOXA11-AS overexpression might be a convinced unfavorable prognostic factor that helps the clinical decision-making process.

Clinicopathological analysis of 598 malignant lymphomas in Taiwan: seven-year experience in a single institution.

PubMed

Lee, Ming-Yuan; Tan, Tran-Der; Feng, An-Chen; Liu, Mei-Ching

2006-08-01

The clinicopathological characteristics of malignant lymphomas vary according to geography. The purpose of this study is to determine the distribution and clinicopathological characteristics of malignant lymphomas in Taiwan. Archival tissue from 598 malignant lymphomas during the period of 1995-2002 was retrieved. They were reclassified according to the World Health Organization classification system. Clinical data, including age, gender, clinical staging, and follow-up, were scrutinized. There were 330 males and 268 females. The median age at onset of disease was 56 years for B-cell lymphoma (BCL), 50 years for T/NK-cell lymphoma (TCL), and 26 years for Hodgkin's lymphoma (HL). BCL accounted for 80.6%, TCL for 12.4%, and HL for 7%. The major subtypes of non-HL were diffuse large B-cell lymphoma, follicular lymphoma, plasma cell myeloma, marginal zone lymphoma of mucosa-associated lymphoid tissue type, mantle cell lymphoma, unspecified peripheral TCL, and nasal type T/NK-cell lymphoma. Nodular sclerosing subtype was the most common in HL. The frequencies of TCL and HL were relatively low. For histological subtype, enteropathy-type TCL and primary bone marrow HL had higher frequency and poorer prognosis. The 5-year overall survival of BCL, TCL, and HL was 58.9, 34.7, and 83.5%, respectively. To the best of our knowledge, this is the largest series study of malignant lymphoma in Taiwan. Immunophenotype, histological subtype, and clinical stage play significant roles in prognosis (P < 0.05).

Prognostic factors for keratocystic odontogenic tumor (odontogenic keratocyst): analysis of clinico-pathologic and immunohistochemical findings in cysts treated by enucleation.

PubMed

Kuroyanagi, Norio; Sakuma, Hidenori; Miyabe, Satoru; Machida, Junichiro; Kaetsu, Atsuo; Yokoi, Motoo; Maeda, Hatsuhiko; Warnakulasuriya, Saman; Nagao, Toru; Shimozato, Kazuo

2009-04-01

The purpose of this study was to determine prognostic factors for the recurrence of keratocystic odontogenic tumors (KCOTs) following simple enucleation by examining clinico-pathologic and immunohistochemical findings. Following enucleation, the frequency of recurrence among 32 subjects diagnosed with KCOT was analyzed for tumor site, radiographic and histologic features, and immunopositivity for Ki-67 and p53. Keratocystic odontogenic tumors in four out of 32 subjects (12.5%) recurred during the follow-up period (median: 33 months, range: 7-114 months). Three out of four subjects (75.0%) among recurrent group showed high expression of Ki-67 (LI >10%) in basal layer and four (4/28; 14.3%) among non-recurrence group (P = 0.025). Expression of p53 among non-recurrent group was observed in 11 subjects (11/28; 39.3%), and in three subjects (3/4; 75.0%) among the recurrent group (P = 0.295). Hazard risk for the recurrence of KCOT was 4.02 (95% CI 1.42-18.14) for high Ki-67 expression in the basal layer by the Cox proportional hazard model (P = 0.009). In our study, none of the other clinico-pathologic variables were associated with the recurrence of KCOT. The results suggested that the evaluation of Ki-67 expression in KCOT at the time of pathological diagnosis might be helpful for consideration of appropriate adjunctive surgical procedures to avoid a recurrence and may serve as a prognostic marker.

Clinicopathological significance and prognostic role of p-STAT3 in patients with hepatocellular carcinoma.

PubMed

Liang, Chaojie; Xu, Yingchen; Ge, Hua; Li, Guangming; Wu, Jixiang

2018-01-01

Constitutive activation of STAT3 through its phosphorylation (p-STAT3) plays a key role in the development and progression of various cancers. However, the relationship between p-STAT3 expression and the clinicopathological features and prognostic value in patients with hepatocellular carcinoma (HCC) remains controversial. We conducted a meta-analysis to evaluate the role of p-STAT3 in HCC. The PubMed, Cochrane Library, Web of Science, EMBASE, Chinese CNKI, and Chinese Wanfang databases were searched using the appropriate terms to find the relevant studies on p-STAT3 and HCC. The relationship between p-STAT3 expression and clinicopathological characteristics and prognostic value was established. Pool odds ratios (ORs) and hazard ratios (HRs) with 95% CIs were calculated using the STATA 14.2 software. The eight articles included in this meta-analysis comprised 752 patients. Expression of p-STAT3 was associated with incidence, age, liver cirrhosis, tumor size, vascular invasion, and TNM stage of HCC, but it was not related to gender, alpha-fetoprotein (AFP), hepatitis B surface antigen (HBsAg), number of tumors, and tumor differentiation. Additionally, the expression of p-STAT3 was related to a poor 3- and 5-year overall survival rate and disease-free survival rate. Expression of p-STAT3 was associated with the incidence, age, liver cirrhosis, tumor size, vascular invasion, and TNM stage. Thus, p-STAT3 can be a reliable prognostic biomarker for HCC. Further high-quality studies with larger numbers of patients are needed.

GFRA3 promoter methylation may be associated with decreased postoperative survival in gastric cancer.

PubMed

Eftang, Lars Lohne; Klajic, Jovana; Kristensen, Vessela N; Tost, Jörg; Esbensen, Qin Ying; Blom, Gustav Peter; Bukholm, Ida Rashida Khan; Bukholm, Geir

2016-03-16

A large number of epigenetic alterations has been found to be implicated in the etiology of gastric cancer. We have studied the DNA methylation status of 27 500 gene promoter regions in 24 gastric adenocarcinomas from a Norwegian cohort, and aimed at identifying the hypermethylated regions. We have compared our findings to the gene expression in the same tissue, and linked our results to prognosis and survival. Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 24 patients following surgical resection of the tumor. Genome-wide DNA methylation profiling of the tumor and matched non-cancerous mucosa was performed. The results were compared to whole transcriptome cDNA microarray analysis of the same material. Most of the gene promoter regions in both types of tissue showed a low degree of methylation, however there was a small, but significant hypermethylation of the tumors. Hierarchical clustering showed separate grouping of the tumor and normal tissue. Hypermethylation of the promoter region of the GFRA3 gene showed a strong correlation to post-operative survival and several of the clinicopathological parameters, however no difference was found between the two main histological types of gastric cancer. There was only a modest correlation between the DNA methylation status and gene expression. The different DNA methylation clusters of the tumors and normal tissue indicate that aberrant DNA methylation is a distinct feature of gastric cancer, although there is little difference in the overall, and low, methylation levels between the two tissue types. The GFRA3 promoter region showed marked hypermethylation in almost all tumors, and its correlation with survival and other clinicopathological parameters may have important prognostic significance.

The CpG island methylator phenotype may confer a survival benefit in patients with stage II or III colorectal carcinomas receiving fluoropyrimidine-based adjuvant chemotherapy

PubMed Central

2011-01-01

Background Colorectal carcinoma (CRC) with CpG island methylator phenotype (CIMP) is recognized as a distinct subgroup of CRC, and CIMP status affects prognosis and response to chemotherapy. Identification of CIMP status in CRC is important for proper patient management. In Eastern countries, however, the clinicopathologic and molecular characteristics and prognosis of CRCs with CIMP are still unclear. Methods A total of 245 patients who underwent their first surgical resection for sporadic CRC were enrolled and CIMP status of the CRCs was determined using the quantitative MethyLight assay. The clinicopathologic and molecular characteristics were reviewed and compared according to CIMP status. In addition, the three-year recurrence-free survival (RFS) of 124 patients with stage II or stage III CRC was analyzed in order to assess the effectiveness of fluoropyrimidine-based adjuvant chemotherapy with respect to CIMP status. Results CIMP-high CRCs were identified in 34 cases (13.9%), and were significantly associated with proximal tumor location, poorly differentiated carcinoma, mucinous histology, and high frequencies of BRAF mutation, MGMT methylation, and MSI-high compared to CIMP-low/negative carcinomas. For patients with stage II or III CIMP-low/negative CRCs, no significant difference was found in RFS between those undergoing surgery alone and those receiving surgery with fluoropyrimidine-based adjuvant chemotherapy. However, for patients with CIMP-high CRCs, patients undergoing surgery with fluoropyrimidine-based adjuvant chemotherapy (n = 17; three-year RFS: 100%) showed significantly better RFS than patients treated with surgery alone (n = 7; three-year RFS: 71.4%) (P = 0.022). Conclusions Our results suggest that selected patients with CIMP-high CRC may benefit from fluoropyrimidine-based adjuvant chemotherapy with longer RFS. Further large scale-studies are required to confirm our results. PMID:21827707

Adrenocortical Carcinoma in Children: A Clinicopathological Analysis of 41 Patients at the Mayo Clinic from 1950 to 2017.

PubMed

Gupta, Nidhi; Rivera, Michael; Novotny, Paul; Rodriguez, Vilmarie; Bancos, Irina; Lteif, Aida

2018-05-25

Adrenocortical carcinoma (ACC) is an aggressive childhood cancer. Limited evidence exists on a definite histopathological criterion to differentiate ACC from adrenocortical adenoma. The aim of this study was to investigate the clinicopathological data of children with ACC, identify prognostic factors, and validate a histopathological criterion to differentiate ACC from adrenocortical adenoma. This retrospective cohort included 41 children, followed at the Mayo Clinic from 1950 to 2017 (onset of symptoms ≤21 years). Outcomes of interest were: alive with no evidence of disease, alive with evidence of disease, and dead of disease. Median age at onset of symptoms was 15.7 years (n = 41; range, 0.2-21 years). Female:male ratio was 3.6: 1. Mixed symptomatology (> 1 hormone abnormality) was the most common presentation (54%, n = 22). Sixty-six percent of patients (n = 27 out of 41) underwent total adrenalectomy. Metastatic disease was more common in children aged > 12 years (p = 0.002 compared to < 4 years). The most common sites of metastases were the liver and lungs. Overall 2-year and 5-year survival rates were 61% (95% CI 45-77) and 46% (95% CI 30-62), respectively. Metastasis at the time of diagnosis was independently associated with poor prognosis (risk ratio 13.7%; 95% CI 3.9-87.7). Weiss criteria (29%) and modified Weiss criteria (33%) were less accurate in younger patients (< 12 years), compared to the Wieneke index (100%). The presence of metastases was an independent prognostic factor. The Wieneke index was the most accurate in predicting clinical outcomes in younger children. © 2018 S. Karger AG, Basel.

Lymphocytic Esophagitis: An emerging clinicopathologic disease associated with dysphagia

PubMed Central

Pasricha, Sarina; Gupta, Amit; Reed, Craig C.; Speck, Olga; Woosley, John T.; Dellon, Evan S.

2016-01-01

Background Lymphocytic Esophagitis (LyE) is a recently described clinicopathological condition, but little is known about its features and clinical associations. Aim To characterize patients with LyE, compare them to non-LyE controls, and identify risk factors. Methods We conducted a retrospective study of all patients ≥18 years old who underwent upper endoscopy with esophageal biopsy between January 1, 2000 and June 1, 2012. Archived pathology slides were re-reviewed and LyE was diagnosed if there was lymphocyte-predominant esophageal inflammation with no eosinophils or granulocytes. Three non-LyE controls groups were also defined: reflux, eosinophilic esophagitis (EoE), and normal. Clinical data were extracted from electronic medical records, and LyE cases were compared to non-LyE controls. Results 27 adults were diagnosed with LyE, and the majority were female (63%). The most common symptom was dysphagia (70%). 52% had a prior or current diagnosis of reflux. Endoscopic findings included strictures (37%), erosive esophagitis (33%), rings (26%), and hiatal hernia (26%); 33% of patients required dilation. After histology re-review, 78% of LyE patients were found to have more than 20 lymphs/hpf. In comparison to the normal, reflux and EoE controls, patients with LyE tended to be non-white (p<0.01), were more commonly tobacco users (p=0.02), and less likely to have seasonal allergies (p=0.02). Conclusion LyE commonly presents with dysphagia due to esophageal strictures which require dilation. Smoking was associated with LyE whereas atopy was not. LyE should be considered as a diagnostic possibility in patients with these characteristics undergoing upper endoscopy. PMID:27343035

Preoperative enteral access is not necessary prior to multimodality treatment of esophageal cancer.

PubMed

Jenkins, Thomas K; Lopez, Alexandra N; Sarosi, George A; Ben-David, Kfir; Thomas, Ryan M

2018-04-01

Surgical enteral access prior to multimodality treatment for esophageal cancer is controversial as dysphagia is often used for feeding tube referral. We hypothesized that enteral access before neoadjuvant chemoradiation for esophageal cancer provides no benefit compared to that placed during definitive esophagectomy. Patients undergoing esophagectomy for esophageal malignancy from 2007 - 2014 were retrospectively identified. Clinicopathologic factors were recorded including preoperative enteral access, weight change, nutritional laboratory works, and perioperative complications. Of 156 identified patients, 99 (63.5%) received neoadjuvant chemoradiation and comprised the study cohort. Fifty (50.5%) underwent enteral access (gastrostomy [14], jejunostomy [32], other [4]; "Access Group") prior to chemoradiation followed by esophagectomy and were compared to 49 "No-Access" patients who underwent enteral access during esophagectomy. Clinicopathologic variables were similar between cohorts. The Access and No-Access cohorts had similar reported dysphagia (86% vs 75.5%, respectively; P = .2) and mean preesophagectomy serum albumin (3.9 vs 4 gm/dL, respectively; P = .2). Weight loss ± 6-month periesophagectomy was similar between access versus No-Access cohorts (-11.2% vs -15.4%, respectively; P = .1). Weight loss during this period was likewise similar for patients with dysphagia in the Access (-11%) versus No-Access group (-15.2%, P = .1). No difference in complication rates was noted between Access (64%) and No-Access groups (51%, P = .2). Despite healthcare provider bias, there seems to be no nutritional or perioperative benefit for enteral access before neoadjuvant chemoradiation for esophageal malignancy. Patients with esophageal malignancy should therefore proceed to appropriate neoadjuvant and surgical therapy with enteral access performed during definitive resection or reserved for those with frank obstruction on endoscopy. Published by Elsevier Inc.

Effects of long-term oral administration of levothyroxine sodium on serum thyroid hormone concentrations, clinicopathologic variables, and echocardiographic measurements in healthy adult horses.

PubMed

Frank, Nicholas; Buchanan, Benjamin R; Elliott, Sarah B

2008-01-01

To determine the effects of long-term oral levothyroxine sodium (L-T(4)) administration on serum thyroid hormone concentrations, thyroid gland function, clinicopathologic variables, and echocardiographic examination measurements in adult euthyroid horses. 6 healthy adult mares. Horses received L-T(4) (48 mg/d) orally for 48 weeks. Every 4 weeks, physical examinations were performed; blood samples were collected for CBC, plasma biochemical analyses, and assessments of serum total triiodothyronine (tT(3)) and thyroxine (tT(4)) concentrations. Plasma creatine kinase MB activity and cardiac troponin I concentration were also measured. Echocardiographic examinations were performed before and at 16, 32, and 48 weeks during the treatment period. During the treatment period, mean body weight decreased significantly; heart rate varied significantly, but the pattern of variation was not consistent. Significant time effects were detected for certain clinicopathologic variables, but mean values remained within reference ranges. Cardiac troponin I was only detectable in 8 of 24 plasma samples (concentration range, 0.01 to 0.03 ng/mL). Serum creatine kinase MB activity did not change significantly over time. Compared with the pretreatment value, 5.4-, 4.0-, and 3.7-fold increases in mean serum tT(4) concentrations were detected at 16, 32, and 48 weeks, respectively. Some cardiac measurements changed significantly over time, but mean values remained within published reference ranges. Mean fractional shortening was lower than the pretreatment mean value at 16 and 32 weeks. In horses, long-term oral administration of 48 mg of L-T(4)/d significantly increased serum tT(4) concentrations and did not appear to adversely affect health.

Heterogeneous clinicopathological features of intraductal carcinoma of the prostate: a comparison between "precursor-like" and "regular type" lesions.

PubMed

Miyai, Kosuke; Divatia, Mukul K; Shen, Steven S; Miles, Brian J; Ayala, Alberto G; Ro, Jae Y

2014-01-01

Intraductal carcinoma of the prostate (IDC-P) has been described as a lesion associated with intraductal spread of invasive carcinoma and consequently aggressive disease. However, there are a few reported cases of pure IDC-P without an associated invasive component, strongly suggesting that this subset of IDC-P may represent a precursor lesion. We compared the clinicopathological features between the morphologically "regular type" IDC-P and "precursor-like" IDC-P. IDC-P was defined as follows; 1) solid/dense cribriform lesions or 2) loose cribriform/micropapillary lesions with prominent nuclear pleomorphism and/or non-focal comedonecrosis. We defined precursor-like IDC-P as follows; 1) IDC-P without adjoining invasive adenocarcinoma but carcinoma present distant from the IDC-P or 2) IDC-P having adjoining invasive microcarcinoma (less than 0.05 ml) and showing a morphologic transition from high-grade prostatic intraepithelial neoplasia (HGPIN) to the IDC-P. IDC-P lacking the features of precursor-like IDC-P was categorized as regular type IDC-P. Of 901 radical prostatectomies performed at our hospital, 141 and 14 showed regular type IDC-P and precursor-like IDC-P in whole-mounted specimens, respectively. Regular type IDC-P cases had significantly higher Gleason score, more frequent extraprostatic extension and seminal vesicle invasion, more advanced pathological T stage, and lower 5-year biochemical recurrence-free rate than precursor-like IDC-P cases. Multivariate analysis revealed nodal metastasis and the presence of regular type IDC-P as independent predictors for biochemical recurrence. Our data suggest that IDC-P may be heterogeneous with variable clinicopathological features. We also suggest that not all IDC-P cases represent intraductal spread of pre-existing invasive cancer, and a subset of IDC-P may be a precursor lesion.

Impact of epidermal growth factor receptor protein and gene alteration on Taiwanese hepatocellular carcinomas.

PubMed

Su, Yu-Hung; Ng, Kwai-Fong; Yu, Ming-Chin; Wu, Ting-Jung; Yeh, Ta-Sen; Lee, Wei-Chen; Lin, Yong-Shiang; Hsieh, Tsung-Han; Lin, Chun-Yen; Yeh, Chau-Ting; Chen, Tse-Ching

2015-09-01

Epidermal growth factor receptor (EGFR) overexpression is associated with disease progression and poor survival in a variety of solid tumors. The role of EGFR in hepatocellular carcinoma (HCC) remains controversial. One hundred thirty-eight HCCs were analyzed for total EGFR (t-EGFR) and phospho-EGFR (p-EGFR) expression and gene amplification using immunohistochemistry and fluorescence in situ hybridization. The role of EGFR was analyzed in relation to the clinicopathological features. Weak to strong p-EGFR immunostaining was noted in 42 of the 138 HCCs. p-EGFR expression correlated with alcoholism (P = 0.03) and chronic hepatitis B infection (P = 0.041). There was no correlation between t-EGFR expression and any of the clinicopathological features. Amplification of the EGFR gene was not identified in the 138 HCCs, but 39.1% of the HCCs showed balanced polysomy of both the EGFR gene and centromere 7. Moreover, 65 tumors showed > 2.2 copies per tumor cell. EGFR copy number gain (CNG) was significantly correlated with gender (P = 0.0491), tumor grade (P = 0.006), and vascular invasion (P = 0.005). HCCs with EGFR CNG also had a poor recurrence-free survival (RFS), as compared with HCCs without EGFR CNG (P = 0.031). When exploring the impact of gender, a significant association of EGFR CNG was found with tumor grade (P = 0.044) and cirrhosis (P = 0.015) exclusively in the male group only; however, the OS and RFS analysis show no significant difference between male and female groups. EGFR CNG was related to crucial clinicopathological features and early recurrence, indicating that EGFR CNG might be a poor prognosis factor for Taiwanese HCC. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Decreased expression of ten-eleven translocation 1 protein is associated with some clinicopathological features in gastric cancer.

PubMed

Frycz, Bartosz Adam; Murawa, Dawid; Borejsza-Wysocki, Maciej; Marciniak, Ryszard; Murawa, Paweł; Drews, Michał; Kołodziejczak, Anna; Tomela, Katarzyna; Jagodziński, Paweł Piotr

2014-03-01

A decrease in ten-eleven translocation 1 (TET1) transcript and 5-Hydroxymethylcytosine (5hmC) levels has recently been demonstrated in primary gastric cancer (GC). However, little is known about TET1 protein levels in gastric tumoral and nontumoral tissue. Therefore, using reverse transcription, real-time quantitative polymerase chain reaction and western blotting analysis, we determined the TET1 transcript and protein levels in tumoral and nontumoral tissue from 38 patients with GC. We also assessed the association between the decrease in TET1 transcript and protein levels and some clinicopathological features in primary GC. We found significantly decreased levels of TET1 transcript (P=0.0023) and protein (P=0.00024) in primary tumoral tissues as compared to nontumoral tissues in patients with GC. Moreover, we also observed significantly lower amounts of TET1 transcript (P=0.03) and protein (P=0.00018) in tumoral tissues in patients aged>60. We also found significant lowered TET1 protein levels in male patients (P=0.0014), stomach (P=0.044) and cardia (P=0.013) tumor localization, T3 depth of invasion (P=0.019), N1 (P=0.012) and N3 lymph node metastasis (P=0.013) and G3 histological grade (P=0.0012). There were also significant decreases in TET1 transcript levels in female patients (P=0.042), intestinal histological types (P=0.0079) and T4 depth of invasion (P=0.037). Our results demonstrated that a decrease in TET1 transcript and protein levels is associated with some clinicopathological features in GC. Copyright © 2014. Published by Elsevier Masson SAS.

Clinicopathological characteristics including BRAF V600E mutation status and PET/CT findings in papillary thyroid carcinoma.

PubMed

Choi, Eun Kyoung; Chong, Ari; Ha, Jung-Min; Jung, Chan Kwon; O, Joo Hyun; Kim, Sung Hoon

2017-07-01

We assessed the associations between FDG uptake in primary papillary thyroid carcinomas (PTCs) and clinicopathological features, including the BRAF V600E mutation, using quantitative and qualitative analyses of preoperative PET/CT data. This was a retrospective review of 106 patients with PTC who underwent PET/CT scans between February 2009 and January 2011 before undergoing total thyroidectomy. Data collected from surgical specimens were compared with FDG uptake in the primary tumour using quantitative and qualitative analyses of preoperative PET/CT data. Clinicopathological data included the primary tumour size, subtype, capsular invasion, extrathyroid extension, multifocality, BRAF V600E mutation status, lymph node metastasis and distant metastasis. The SUVmax of the primary tumour was significantly higher in patients with a primary tumour >1 cm, extrathyroid extension or the BRAF V600E mutation than in patients without these features (P<.001, .049 and <.001). Univariate analyses showed that primary tumour size, extrathyroid extension and BRAF V600E mutation status were associated with the SUVmax of the PTC. Multivariate analysis indicated that primary tumour size and the BRAF V600E mutation were associated with the SUVmax of the PTC. In a visual assessment, the primary tumour size was larger in FDG-avid than in non-FDG-avid PTCs (P<.001). There was no significant difference in the presence of multifocality, thyroid capsular invasion, extrathyroid extension, BRAF V600E mutation, lymph node metastasis or distant metastasis between FDG-avid and non-FDG-avid PTCs. Primary tumour size and the BRAF V600E mutation are significant factors associated with the SUVmax on preoperative PET/CT in patients with PTC. © 2017 John Wiley & Sons Ltd.

Tracking the Correlation Between CpG Island Methylator Phenotype and Other Molecular Features and Clinicopathological Features in Human Colorectal Cancers: A Systematic Review and Meta-Analysis

PubMed Central

Zong, Liang; Abe, Masanobu; Ji, Jiafu; Zhu, Wei-Guo; Yu, Duonan

2016-01-01

Objectives: The controversy of CpG island methylator phenotype (CIMP) in colorectal cancers (CRCs) persists, despite many studies that have been conducted on its correlation with molecular and clinicopathological features. To drive a more precise estimate of the strength of this postulated relationship, a meta-analysis was performed. Methods: A comprehensive search for studies reporting molecular and clinicopathological features of CRCs stratified by CIMP was performed within the PubMed, EMBASE, and Cochrane Library. CIMP was defined by either one of the three panels of gene-specific CIMP markers (Weisenberger panel, classic panel, or a mixture panel of the previous two) or the genome-wide DNA methylation profile. The associations of CIMP with outcome parameters were estimated using odds ratio (OR) or weighted mean difference (WMD) or hazard ratios (HRs) with 95% confidence interval (CI) for each study using a fixed effects or random effects model. Results: A total of 29 studies involving 9,393 CRC patients were included for analysis. We observed more BRAF mutations (OR 34.87; 95% CI, 22.49–54.06) and microsatellite instability (MSI) (OR 12.85 95% CI, 8.84–18.68) in CIMP-positive vs. -negative CRCs, whereas KRAS mutations were less frequent (OR 0.47; 95% CI, 0.30–0.75). Subgroup analysis showed that only the genome-wide methylation profile-defined CIMP subset encompassed all BRAF-mutated CRCs. As expected, CIMP-positive CRCs displayed significant associations with female (OR 0.64; 95% CI, 0.56–0.72), older age at diagnosis (WMD 2.77; 95% CI, 1.15–4.38), proximal location (OR 6.91; 95% CI, 5.17–9.23), mucinous histology (OR 3.81; 95% CI, 2.93–4.95), and poor differentiation (OR 4.22; 95% CI, 2.52–7.08). Although CIMP did not show a correlation with tumor stage (OR 1.10; 95% CI, 0.82–1.46), it was associated with shorter overall survival (HR 1.73; 95% CI, 1.27–2.37). Conclusions: The meta-analysis highlights that CIMP-positive CRCs take their own molecular feature, especially overlapping with BRAF mutations, and clinicopathological features and worse prognosis from CIMP-negative CRCs, suggesting CIMP could be used as an independent prognostic marker for CRCs. PMID:26963001

Tracking the Correlation Between CpG Island Methylator Phenotype and Other Molecular Features and Clinicopathological Features in Human Colorectal Cancers: A Systematic Review and Meta-Analysis.

PubMed

Zong, Liang; Abe, Masanobu; Ji, Jiafu; Zhu, Wei-Guo; Yu, Duonan

2016-03-10

The controversy of CpG island methylator phenotype (CIMP) in colorectal cancers (CRCs) persists, despite many studies that have been conducted on its correlation with molecular and clinicopathological features. To drive a more precise estimate of the strength of this postulated relationship, a meta-analysis was performed. A comprehensive search for studies reporting molecular and clinicopathological features of CRCs stratified by CIMP was performed within the PubMed, EMBASE, and Cochrane Library. CIMP was defined by either one of the three panels of gene-specific CIMP markers (Weisenberger panel, classic panel, or a mixture panel of the previous two) or the genome-wide DNA methylation profile. The associations of CIMP with outcome parameters were estimated using odds ratio (OR) or weighted mean difference (WMD) or hazard ratios (HRs) with 95% confidence interval (CI) for each study using a fixed effects or random effects model. A total of 29 studies involving 9,393 CRC patients were included for analysis. We observed more BRAF mutations (OR 34.87; 95% CI, 22.49-54.06) and microsatellite instability (MSI) (OR 12.85 95% CI, 8.84-18.68) in CIMP-positive vs. -negative CRCs, whereas KRAS mutations were less frequent (OR 0.47; 95% CI, 0.30-0.75). Subgroup analysis showed that only the genome-wide methylation profile-defined CIMP subset encompassed all BRAF-mutated CRCs. As expected, CIMP-positive CRCs displayed significant associations with female (OR 0.64; 95% CI, 0.56-0.72), older age at diagnosis (WMD 2.77; 95% CI, 1.15-4.38), proximal location (OR 6.91; 95% CI, 5.17-9.23), mucinous histology (OR 3.81; 95% CI, 2.93-4.95), and poor differentiation (OR 4.22; 95% CI, 2.52-7.08). Although CIMP did not show a correlation with tumor stage (OR 1.10; 95% CI, 0.82-1.46), it was associated with shorter overall survival (HR 1.73; 95% CI, 1.27-2.37). The meta-analysis highlights that CIMP-positive CRCs take their own molecular feature, especially overlapping with BRAF mutations, and clinicopathological features and worse prognosis from CIMP-negative CRCs, suggesting CIMP could be used as an independent prognostic marker for CRCs.

Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

PubMed Central

Qin, Dan-dan; Wu, Li-hua; Song, Yan; Yu, Feng; Wang, Su-xia; Liu, Gang; Zhao, Ming-hui

2015-01-01

Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. Design A retrospective cohort study. Participants Seventy-nine patients with renal biopsy-proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. Results In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn’t reach statistical meanings (P = 0.104). Conclusion Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID:26544865

The presence and prognostic significance of human papillomavirus in squamous cell carcinoma of the larynx.

PubMed

Erkul, Evren; Yilmaz, Ismail; Narli, Gizem; Babayigit, Mustafa Alparslan; Gungor, Atila; Demirel, Dilaver

2017-07-01

The aim of the present study was to evaluate the role of HPV in laryngeal squamous cell carcinoma and correlate it with patients' clinicopathological data. In total, 78 laryngeal squamous cell carcinoma patients enrolled in this study. The presence of genotype-specific HPV DNA was evaluated using Genotyping Assay in formalin-fixed paraffin-embedded tissue which was diagnosed between 2005 and 2015. All samples were also evaluated for p16 immunohistochemical staining. HPV DNA and p16 status were assessed in terms of location, smoking, alcohol consumption, lymph node status, tumor stage, overall survival, disease-free survival, perineural invasion, and vascular invasion retrospectively. Five test samples were excluded from the study due to inadequate deoxyribonucleic acid purity. HPV DNA was detected in 19 of 73 (26.02%) in patients with laryngeal squamous cell carcinoma. Human papilloma virus genotyping revealed double human papilloma virus in one case (types 16 and 59) and HPV 16 in the remaining cases. Although HPV-positive cases showed slightly better 3 years survival than HPV-negative ones, this finding was not statistically significant (overall survival p = 0.417, HPV positive: 92.3%, HPV negative: 81.4%, and disease-free survival p = 0.526, HPV positive: 93.8%, HPV negative: 80.9%). The presence of HPV DNA was not significantly associated with any clinicopathological features (p > 0.05). Among 73 patients, only 4 had an immunohistochemical staining of p16 and these patients were also HPV DNA 16 positive. Although our study results revealed a slightly better survival in patients with HPV DNA positivity for HPV 16 compared to the negative ones, the difference was not statistically significant. However, an increasing rate in especially high-risk-type HPV-16 prevalence in laryngeal squamous cell carcinoma by RT-PCR method was observed compared to our previous study. Although the presence of HPV in laryngeal SCCs seems to be associated with slightly better prognosis, additional studies may be needed, since our results were not statistically significant. We believed that HPV is not an adequate biomarker for diagnostic and prognostic purposes in laryngeal squamous cell carcinoma.

[Ewing sarcoma osseous and extraosseous : a clinicopathologic study of 29 cases].

PubMed

Ayadi, Lobna; Chaari, Chiraz; Kallel, Rim; Ayadi, Kamel; Khabir, Abdelmajid; Jlidi, Rachid; Daoud, Jamel; Frikha, Mounir; Makni, Saloua; Sellami-Boudawara, Tahya

2010-05-01

Ewing's sarcoma (ES) is a rare tumour accounting for 10% of primary malignant bone tumours in children and 3% of all childhood malignancies. ES belongs to a group of small round cell tumours. In this review, we will describe the main clinicopathological features of this rare tumour and discuss its prognosis. We report a retrospective study of 29 cases of ES, of which 4 were extraosseous, diagnosed over a period 11 years (January 1989 - December 1999). Clinicopathological data were described. Hematoxylin-eosin staining and immunohistochemical study were reviewed. 12 patients were male and 17 were female (ratio: 0,8) with a median age of 16 years. 62,5% of tumours were located in flat bone and 33,3% in long bone. The medium size of the tumor was 10,6 cm (range:3-25cm). 27,5% of patients presented with metastatic disease at time of diagnosis. Microscopically, tumour tissue was composed of round, small, blue cells with fine granular chromatin. Tumour cells strongly coexpressed CD99 and vimentin (100%). Systemic treatment consisted of adjuvant chemotherapy (84,2%). Local control was based on and surgery (57,9%) or radiation therapy (36,8%). A good response to chemotherapy was obtained in 37.5%; 13,7% of patients were alive without disease (medium follow up: 169 mois); 34,5% of patients developed metastases (medium follow up : 23 months) and 10,3% developed recurrences (medium follow up :13 months). Our study emphasizes two points : the great size of the tumor and the frequent location in flat bone which may explain the poor prognosis of Ewing sarcoma in our series despite the multidisciplinary treatment.

Relation of glypican-3 and E-cadherin expressions to clinicopathological features and prognosis of mucinous and non-mucinous colorectal adenocarcinoma.

PubMed

Foda, Abd Al-Rahman Mohammad; Mohammad, Mie Ali; Abdel-Aziz, Azza; El-Hawary, Amira Kamal

2015-06-01

Glypican-3 (GPC3) is a member of the membrane-bound heparin sulfate proteoglycans. E-cadherin is an adhesive receptor that is believed to act as a tumor suppressor gene. Many studies had investigated E-cadherin expressions in colorectal carcinoma (CRC) while only one study had investigated GPC3 expression in CRC. This study aims to investigate expression of GCP3 and E-cadherin in colorectal mucinous carcinoma (MA) and non-mucinous adenocarcinoma (NMA) using manual tissue microarray technique. Tumor tissue specimens are collected from 75 cases of MC and 75 cases of NMA who underwent radical surgery from Jan 2007 to Jan 2012 at the Gastroenterology Centre, Mansoura University, Egypt. Their clinicopathological parameters and survival data were revised and analyzed using established statistical methodologies. High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique and immunohistochemistry for GPC3 and E-cadherin was done. NMA showed higher expression of GPC3 than MA with no statistically significant relation. NMA showed a significantly higher E-cadherin expression than MA. GPC3 and E-cadherin positivity rates were significantly interrelated in NMA, but not in MA, group. In NMA group, there was no significant relation between either GPC3 or E-cadherin expression and the clinicopathological features. In a univariate analysis, neither GPC3 nor E-cadherin expression showed a significant impact on disease-free survival (DFS) or overall survival (OS). GPC3 and E-cadherin expressions are not independent prognostic factors in CRC. However, expressions of both are significantly interrelated in NMA patients, suggesting an excellent interplay between both, in contrast to MA. Further molecular studies are needed to further explore the relationship between GCP3 and E-cadherin in colorectal carcinogenesis.

Testes-specific protease 50 as an independent risk factor for poor prognosis in patients with non-small cell lung cancer

PubMed Central

Qiao, Wen-Liang; Shi, Bo-Wen; Han, Yu-Dong; Tang, Hua-Mei; Lin, Jun; Hu, Hai-Yang; Lin, Qiang

2018-01-01

Testes-specific protease 50 (TSP50) is normally expressed in the testes and is overexpressed in various types of human cancers, including breast cancer, colorectal carcinoma and laryngocarcinoma. However, little has been reported on the association between TSP50 and non-small cell lung cancer (NSCLC). The present study aimed to detect TSP50 expression in 198 strict follow-up cases of paired NSCLC and 15 cases of normal lung parenchymal specimens using immunohistochemical staining. The expression levels of TSP50 were then correlated with the clinicopathological factors of NSCLC to assess its potential diagnostic and prognostic value. The relationship between TSP50 expression and the clinicopathological parameters of NSCLC was evaluated using χ2 and Fisher's exact tests. Survival rates for the overall population (n=198) were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox's proportional hazards regression model. P<0.05 was considered to indicate a statistically significant difference. The expression of TSP50 was significantly increased in NSCLC tissue compared with in adjacent non-tumor or normal lung parenchymal tissue (P<0.001). A significant association was revealed between high expression levels of TSP50 and clinicopathological characteristics including tumor differentiation (P=0.012), late tumor status (P=0.004) and late tumor node metastasis stage (P=0.026), as well as a reduced disease free survival (P=0.009) and overall survival rate (P=0.002) in all patients with NSCLC. Multivariate analyses demonstrated that high TSP50 expression in tumor tissues was significantly associated with a shorter disease-free survival rate [hazard ratio (HR) =1.590, 95% confidence interval (CI): 1.035–2.441], and with a shorter overall survival rate (HR=1.814; 95% CI: 1.156–2.846). In conclusion, the present data demonstrated that increased TSP50 protein expression may be a potential predictor of early recurrence and poor prognosis in NSCLC, and that TSP50 expression levels possess the potential to be used as a biomarker and therapeutic target for the treatment of patients with NSCLC. PMID:29805619

Testes-specific protease 50 as an independent risk factor for poor prognosis in patients with non-small cell lung cancer.

PubMed

Qiao, Wen-Liang; Shi, Bo-Wen; Han, Yu-Dong; Tang, Hua-Mei; Lin, Jun; Hu, Hai-Yang; Lin, Qiang

2018-06-01

Testes-specific protease 50 (TSP50) is normally expressed in the testes and is overexpressed in various types of human cancers, including breast cancer, colorectal carcinoma and laryngocarcinoma. However, little has been reported on the association between TSP50 and non-small cell lung cancer (NSCLC). The present study aimed to detect TSP50 expression in 198 strict follow-up cases of paired NSCLC and 15 cases of normal lung parenchymal specimens using immunohistochemical staining. The expression levels of TSP50 were then correlated with the clinicopathological factors of NSCLC to assess its potential diagnostic and prognostic value. The relationship between TSP50 expression and the clinicopathological parameters of NSCLC was evaluated using χ 2 and Fisher's exact tests. Survival rates for the overall population (n=198) were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox's proportional hazards regression model. P<0.05 was considered to indicate a statistically significant difference. The expression of TSP50 was significantly increased in NSCLC tissue compared with in adjacent non-tumor or normal lung parenchymal tissue (P<0.001). A significant association was revealed between high expression levels of TSP50 and clinicopathological characteristics including tumor differentiation (P=0.012), late tumor status (P=0.004) and late tumor node metastasis stage (P=0.026), as well as a reduced disease free survival (P=0.009) and overall survival rate (P=0.002) in all patients with NSCLC. Multivariate analyses demonstrated that high TSP50 expression in tumor tissues was significantly associated with a shorter disease-free survival rate [hazard ratio (HR) =1.590, 95% confidence interval (CI): 1.035-2.441], and with a shorter overall survival rate (HR=1.814; 95% CI: 1.156-2.846). In conclusion, the present data demonstrated that increased TSP50 protein expression may be a potential predictor of early recurrence and poor prognosis in NSCLC, and that TSP50 expression levels possess the potential to be used as a biomarker and therapeutic target for the treatment of patients with NSCLC.

Clinicopathological Findings of Suicide in the Elderly: Three Cases

ERIC Educational Resources Information Center

Peisah, Carmelle; Snowdon, John; Kril, Jillian; Rodriguez, Michael

2007-01-01

The neuropathological correlates of suicide in older persons have received little research attention. Our recent study of elderly suicide victims from an Australian forensic medicine department (n = 143), unlike a previous case-control study, did not find an increased prevalence of Alzheimer's disease (AD) in older persons who committed suicide…

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma.

PubMed

Ioachim, Elli; Michael, Michalis; Stavropoulos, Nicolaos E; Kitsiou, Evangelia; Salmas, Marios; Malamou-Mitsi, Vasiliki

2005-03-01

To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27-89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression.

The Prognostic and Clinicopathological Roles of Sirtuin-3 in Various Cancers.

PubMed

Yu, Fei-Yuan; Xu, Qian; Wu, Dan-Dan; Lau, Andy T Y; Xu, Yan-Ming

2016-01-01

Sirtuin-3 (SIRT3) is a major mitochondrial NAD(+)-dependent deacetylase and plays a key role in the progression and development of human cancers. Although the prognostic and clinicopathological features of SIRT3 expression in various cancers have been investigated by different research groups, however, inconsistent and opposing results can be observed. In this study, we therefore performed a meta-analysis to evaluate the significance of SIRT3 expression in various cancers. Systematic literature searching was performed in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang Data up to November 2015. Total effect analyses and subgroup analyses were performed to evaluate the relationship between SIRT3 expression and overall survival, cancer/non-cancer tissues, lymph node metastasis, pathological differentiation, tumor node metastasis (TNM) stage, tumor size, and gender, in various cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to clarify the risk or hazard association. A total of 14 studies comprising 2165 cancer patients were included to assess the association between SIRT3 immunohistochemical expression and overall survival or clinicopathological characteristics. SIRT3 expression was significantly associated with overall survival in gastric cancer (HR = 0.62, 95% CI = 0.43-0.89, P = 0.009) and hepatocellular carcinoma patients (HR = 0.56, 95% CI = 0.42-0.74, P<0.0001), cancer/non-cancer tissues in hepatocellular carcinoma patients (OR = 0.04, 95% CI = 0.01-0.16, P<0.0001), lymph node metastasis in breast cancer patients (OR = 2.20, 95% CI = 1.49-3.26, P<0.0001), and also pathological differentiation in hepatocellular carcinoma patients (OR = 0.69, 95% CI = 0.48-0.98, P = 0.04) and gastric cancer patients (OR = 0.33, 95% CI = 0.21-0.50, P<0.00001), by subgroup analyses. Furthermore, SIRT3 expression was significantly associated with pathological differentiation in total effect analysis (OR = 0.46, 95% CI = 0.29-0.74, P = 0.001). No detectable relation between SIRT3 expression and other clinicopathological parameters were found. This meta-analysis indicates that SIRT3 expression level is associated with prognostic and clinical features in specific cancers.

Synchronous Primary Cancers of the Endometrium and Ovary With the Same Histopathologic Type Versus Endometrial Cancer With Ovarian Metastasis: A Single Institution Review of 72 Cases.

PubMed

Bese, Tugan; Sal, Veysel; Kahramanoglu, Ilker; Tokgozoglu, Nedim; Demirkiran, Fuat; Turan, Hasan; Ilvan, Sennur; Arvas, Macit

2016-02-01

The purpose of this study was to evaluate the clinicopathological characteristics and survival outcomes of women with simultaneous endometrial and ovarian carcinomas having the same histopathologic type. A review of medical records from 1997 to 2015 identified 72 patients with simultaneous carcinomas of the endometrium and ovary with the same histopathologic type. Patients with synchronous primary cancers of endometrium and ovary (SCEOs) were compared with patients with primary endometrial cancer with ovarian metastasis (ECOM). Clinical and pathological data were obtained from the patients' medical records. Clinicopathological variables including categorical data were analyzed by χ(2) or Fisher exact test and continuous data by a Student t test. A Kaplan-Meier survival analysis was performed and compared by using the log-rank test. A univariate and multivariate analysis of 72 patients with SCEO with the same histopathologic type revealed that SCEO is an independent prognostic factor of 10-year overall survival. There were 31 patients in the SCEO group and 41 patients in the ECOM group. With a mean follow-up time of 68.2 months, the 10-year overall survival rates were 61.3% and 36.6% in SCEO and ECOM groups, respectively (P = 0.029). Age, menopausal status, stage of ovarian cancer, performing lymphadenectomy, grade of endometrial tumor, omental metastasis, and residual tumor were found to be significant risk factors for recurrence in the synchronous group. The differentiation between SCEO and ECOM is of great clinical importance while our results showed a better prognosis for patients with SCEO compared with patients with ECOM. More aggressive therapeutic approaches may be considered for patients with SCEO who are older, postmenopausal, and/or have advanced grade of endometrial tumor, omental metastasis, and residual tumor. Lymphadenectomy should be performed in every patient with SCEO.

Discovery and Validation of Novel Expression Signature for Postcystectomy Recurrence in High-Risk Bladder Cancer

PubMed Central

Lam, Lucia L.; Ghadessi, Mercedeh; Erho, Nicholas; Vergara, Ismael A.; Alshalalfa, Mohammed; Buerki, Christine; Haddad, Zaid; Sierocinski, Thomas; Triche, Timothy J.; Skinner, Eila C.; Davicioni, Elai; Daneshmand, Siamak; Black, Peter C.

2014-01-01

Background Nearly half of muscle-invasive bladder cancer patients succumb to their disease following cystectomy. Selecting candidates for adjuvant therapy is currently based on clinical parameters with limited predictive power. This study aimed to develop and validate genomic-based signatures that can better identify patients at risk for recurrence than clinical models alone. Methods Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. Genomic (GC) and clinical (CC) classifiers for predicting recurrence were developed on a discovery set (n = 133). Performances of GC, CC, an independent clinical nomogram (IBCNC), and genomic-clinicopathologic classifiers (G-CC, G-IBCNC) were assessed in the discovery and independent validation (n = 66) sets. GC was further validated on four external datasets (n = 341). Discrimination and prognostic abilities of classifiers were compared using area under receiver-operating characteristic curves (AUCs). All statistical tests were two-sided. Results A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. This was higher than individual clinical variables, IBCNC (AUC = 0.73), and comparable to CC (AUC = 0.78). Performance was improved upon combining GC with clinical nomograms (G-IBCNC, AUC = 0.82; G-CC, AUC = 0.86). G-CC high-risk patients had elevated recurrence probabilities (P < .001), with GC being the best predictor by multivariable analysis (P = .005). Genomic-clinicopathologic classifiers outperformed clinical nomograms by decision curve and reclassification analyses. GC performed the best in validation compared with seven prior signatures. GC markers remained prognostic across four independent datasets. Conclusions The validated genomic-based classifiers outperform clinical models for predicting postcystectomy bladder cancer recurrence. This may be used to better identify patients who need more aggressive management. PMID:25344601

Enteropathy-associated T-cell lymphoma--a clinicopathologic and array comparative genomic hybridization study.

PubMed

Ko, Young Hyeh; Karnan, Sivasundaram; Kim, Kyeong Mee; Park, Cheol Keun; Kang, Eun Suk; Kim, Young Ho; Kang, Won Ki; Kim, Seok Jin; Kim, Won Seog; Lee, Woo Yong; Chun, Ho Kyung; Seto, Masao

2010-09-01

According to the new World Health Organization classification system, there are 2 types of enteropathy-associated T-cell lymphoma. Type 1 is associated with celiac disease and accounts for the majority of cases in Western countries, whereas type 2 is not associated with celiac disease. To characterize enteropathy-associated T-cell lymphoma types in Korea, we carried out clinicopathologic and immunophenotypic analyses of 8 Koreans with enteropathy-associated T-cell lymphoma and investigated genomic profile using array comparative genomic hybridization. The tumors involved the small intestine in 5 patients and the colorectum in 3 patients. Two patients carried an HLA DQB10302 allele that corresponds to HLA DQ8. None of the patients had gluten-sensitive malabsorption syndrome. Intraepithelial lymphocytosis was observed in all patients. The sizes of the tumor cells were small or small-to-medium in 7 cases and medium-to-large in 1 case. The immunophenotypes of the tumor cells were CD4-CD8+CD56+ in 4 cases, CD4-CD8+CD56- in 1 case, CD4-CD8-CD56+ in 2 cases, and CD4-CD8-CD56- in 1 case. Array comparative genomic hybridization analysis showed that chromosome 9q33-q34.1 gain was present in 4 (80%) of the 5 cases examined. Other recurrent genomic alterations were gain of 6p21.1-21.31 (3/5, 60%), gain of 19q (2/5), and the loss of 3p12.1-p12.2 (2/5) and 3q26.31 (2/5). These results suggest that the most prevalent type of enteropathy-associated T-cell lymphoma in this geographic region is type 2, and the genetic changes associated with it are similar to those in Western countries. Copyright 2010 Elsevier Inc. All rights reserved.

CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features.

PubMed

Bauman, Tyler M; Ewald, Jonathan A; Huang, Wei; Ricke, William A

2015-07-25

CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable analysis.

The notch pathway is activated in neoplastic progression in esophageal squamous cell carcinoma.

PubMed

Lubin, Daniel J; Mick, Rosemarie; Shroff, Stuti G; Stashek, Kristen; Furth, Emma E

2018-02-01

The Notch signaling pathway is integral to normal human development and homeostasis and has a deterministic function on cell differentiation. Recent studies suggest aberrant Notch signaling may contribute to neoplastic progression by an increase in stem cell survival, chemoresistance, and the promotion of epithelial-to-mesenchymal transition. The goals of our study were to determine, utilizing quantitative technologies, the expression of activated Notch 1 in esophageal squamous cell carcinoma (SCC) and to determine the relationship between Notch 1 expression and various clinicopathologic parameters. Immunohistochemical staining for Notch intracellular domain (NICD) was performed on 60 consecutive cases of esophageal squamous cell carcinoma, 42 cases of benign esophageal squamous epithelium, and 13 cases of eosinophilic esophagitis diagnosed in our department from 2007 through 2015, and exact nuclear staining and nuclear characteristics were graded using the Vectra imaging system. Clinicopathologic data (gender, age at diagnosis, smoking status, tumor grade, tumor stage, tumor location, and survival) were collected for each SCC case and these were correlated with NICD staining. Cases of esophageal SCC demonstrated significantly higher NICD staining compared to cases of benign and reactive esophageal epithelium (P=.003 and .005, respectively). Among cases of esophageal SCC, nuclear NICD staining was significantly correlated with both tumor grade and stage. Following classification and regression tree analysis, esophageal SCC patients with increased NICD expression were found to be more likely to die from their disease than those with lower levels of expression. Taken together, the findings suggest that increased Notch 1 may contribute to the development and aggressiveness of esophageal SCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Neuroendocrine tumours of the ampulla of Vater: clinico-pathological features, surgical approach and assessment of prognosis.

PubMed

Dumitrascu, Traian; Dima, Simona; Herlea, Vlad; Tomulescu, Victor; Ionescu, Mihnea; Popescu, Irinel

2012-08-01

Neuroendocrine tumours occur very rarely in the ampulla of Vater and their clinical behaviour is unknown. The aim of this study is to assess the clinico-pathological features, surgical approach and prognosis of these patients. Six patients with neuroendocrine tumours of the ampulla of Vater treated with curative intent surgery at a single centre were retrospectively analysed. A univariate analysis of potential prognostic factors was also performed (data provided from the present study and literature review). Pancreaticoduodenectomy was curative in all the patients. Overall and disease-free survival rates were significantly better for G1/G2 tumours (p = 0.006 and p = 0.004, respectively). Although frequent, lymph node metastases did not influenced both overall (p = 0.760) and disease-free survival rates (p = 0.745). No significant differences of survival were observed in patients with ENETS stage I/II disease, as compared to ENETS stage III disease (p = 0.169 and p = 0.137, respectively). No differences were observed according to UICC staging system (p = 0.073 and p = 0.177, respectively). Tumours that are less than 2 cm or limited to the ampulla appear to have a better prognosis. The WHO 2010 classification appear to accurately predict patient prognosis, while the ENETS or UICC staging systems have a limited value (especially in regard to lymph node metastases). Radical surgery (i.e. pancreaticoduodenectomy with lymphadenectomy) should be the standard approach in most patients with NET of the ampulla of Vater because this procedure removes all the potential tumour-bearing tissue.

p16 protein is upregulated in a stepwise fashion in colorectal adenoma and colorectal carcinoma.

PubMed

Al-Ahwal, Mahmoud; Gomaa, Wafaey; Emam, Eman; Qari, Yousif; Buhmeida, Abdelbaset; Radwi, Salman; Al-Maghrabi, Basim; Al-Qahtani, Mohammad; Al-Maghrabi, Jaudah

2016-11-01

p16 is tumor suppressor gene acting as a cell cycle regulator. The present study was conducted to compare p16 expression in normal, dysplastic, and malignant colonic mucosae, and to explore its relation to clinicopathological variables and follow-up data in colorectal carcinoma (CRC). Tissue microarrays were performed from 25 normal colonic mucosae, 41 colonic adenomas, and 191 CRC, with corresponding 50 nodal metastases. Immunohistochemistry was performed using anti-p16 antibody, sections were scored, and statistical analysis was performed. K-ras mutation detection was also performed. Immunoexpression of p16 was significantly higher in CRC than in adenomas (P = 0.033) and normal colonic mucosa (P = 0.005). There was no statistically significant difference between p16 expression in CRC and nodal metastasis. There was no significant association between p16 immunoexpression in CRC and all clinicopathological data and survival probability. K-ras mutations were detected in 34% of CRC. However, there was no correlation between K-ras status and p16 expression (P = 0.325). Absence of p16 expression is correlated to a benign course of CRC adenomas. p16 has a key role in CRC progression and can be used as a marker for colorectal adenoma. On the other hand, it has no role as a predictive and/or prognostic factor in CRC. Further extended studies are required to explore the role of p16 as indicator of premalignant lesions in the colon and to test its relation with CRC histological grade, as well as to test its value as a new therapeutic target.

Coexistence of chronic lymphocytic thyroiditis is associated with lower recurrence rates in patients with papillary thyroid carcinoma.

PubMed

Kim, Eui Young; Kim, Won Gu; Kim, Won Bae; Kim, Tae Yong; Kim, Jung Min; Ryu, Jin-Sook; Hong, Suck Joon; Gong, Gyungyub; Shong, Young Kee

2009-10-01

The effect of coexistent chronic lymphocytic thyroiditis (CLT) on prognosis in papillary thyroid carcinoma (PTC) patients remains controversial. We evaluated the influence of coexistent CLT on prognostic outcome and the association of coexistent CLT with clinicopathological parameters. A retrospective study with a median follow-up of 70 months. Patients with PTC who underwent total thyroidectomy followed by (131)I remnant ablation between 1995 and 2003 at Asan Medical Center, Seoul, Korea were enrolled. CLT was diagnosed histopathologically. Among 1441 patients, 214 (14.9%) had coexistent CLT. A greater female preponderance was noted in the patients with CLT compared with those without CLT (P < 0.01). Mean tumour size in the patients with CLT was smaller than that in patients without CLT (2.0 +/- 1.2 vs. 2.2 +/- 1.4 cm; P = 0.02). One hundred and fifty-one (12.3%) patients without CLT had recurrence, whereas 14 (7.1%) patients with CLT had recurrence during the follow-up period (P = 0.016). In patients with cervical lymph node metastases, those with coexistent CLT showed a significantly lower recurrence rate than those without CLT (P = 0.012). However, this association was lost on multivariate analysis adjusting for other clinicopathological predictors for recurrence. In this study, CLT was commonly associated with PTC and was associated with smaller size of the primary tumour at presentation. CLT was also associated with a reduced risk of recurrence during follow-up, although this was not significant after adjustment for other prognostic factors.

Clinicopathological characteristics of patients with upper urinary tract urothelial cancer with loss of immunohistochemical expression of the DNA mismatch repair proteins in universal screening.

PubMed

Urakami, Shinji; Inoshita, Naoko; Oka, Suguru; Miyama, Yu; Nomura, Sachio; Arai, Masami; Sakaguchi, Kazushige; Kurosawa, Kazuhiro; Okaneya, Toshikazu

2018-02-01

To assess the detection rate of putative Lynch syndrome-associated upper urinary tract urothelial cancer among all upper urinary tract urothelial cancers and to examine its clinicopathological characteristics. A total of 143 patients with upper urinary tract urothelial cancer who had received total nephroureterectomy were immunohistochemically stained for the expression of mismatch repair proteins MLH1, PMS2, MSH2 and MSH6. For all suspected mismatch repair-deficient cases, MMR genetic testing was recommended and clinicopathological features were examined. Loss of mismatch repair proteins was found in seven patients (5%) who were thus categorized as putative Lynch syndrome-associated upper urinary tract urothelial cancer. Five of these patients showed dual loss of MSH2/MSH6. Two patients were confirmed to be MSH2 germline mutation carriers. Histologically, all seven tumors were low-grade atypical urothelial carcinoma and showed its unique histological features, such as an inverted papilloma-like growth pattern and a villous to papillary structure with mild stratification of tumor cells. Six tumors had no invasion of the muscularis propria. No recurrence or cancer-related deaths were reported in these seven patients. Just three patients met the revised Amsterdam criteria. This is the first report that universally examined mismatch repair immunohistochemical screening for upper urinary tract urothelial cancers. The prevalence (5%) of putative Lynch syndrome-associated upper urinary tract urothelial cancers is much higher than we had expected. We ascertained that putative Lynch syndrome-associated upper urinary tract urothelial cancers were clinically in the early stage and histologically classified into low-grade malignancy with its characteristic pathological features. The clinicopathological characteristics that we found in the present study could become additional possible markers in the diagnosis of Lynch syndrome-associated upper urinary tract urothelial cancers. © 2017 The Japanese Urological Association.

Chemokine-like factor-like MARVEL transmembrane domain-containing 3 expression is associated with a favorable prognosis in esophageal squamous cell carcinoma.

PubMed

Han, Tianci; Shu, Tianci; Dong, Siyuan; Li, Peiwen; Li, Weinan; Liu, Dali; Qi, Ruiqun; Zhang, Shuguang; Zhang, Lin

2017-05-01

Decreased expression of human chemokine-like factor-like MARVEL transmembrane domain-containing 3 (CMTM3) has been identified in a number of human tumors and tumor cell lines, including gastric and testicular cancer, and PC3, CAL27 and Tca-83 cell lines. However, the association between CMTM3 expression and the clinicopathological features and prognosis of esophageal squamous cell carcinoma (ESCC) patients remains unclear. The aim of the present study was to investigate the correlation between CMTM3 expression and clinicopathological parameters and prognosis in ESCC. CMTM3 mRNA and protein expression was analyzed in ESCC and paired non-tumor tissues by quantitative real-time polymerase chain reaction, western blotting and immunohistochemical analysis. The Kaplan-Meier method was used to plot survival curves and the Cox proportional hazards regression model was also used for univariate and multivariate survival analysis. The results revealed that CMTM3 mRNA and protein expression levels were lower in 82.5% (30/40) and 75% (30/40) of ESCC tissues, respectively, when compared with matched non-tumor tissues. Statistical analysis demonstrated that CMTM3 expression was significantly correlated with lymph node metastasis (P=0.002) and clinical stage (P<0.001) in ESCC tissues. Furthermore, the survival time of ESCC patients exhibiting low CMTM3 expression was significantly shorter than that of ESCC patients exhibiting high CMTM3 expression (P=0.01). In addition, Kaplan-Meier survival analysis revealed that the overall survival time of patients exhibiting low CMTM3 expression was significantly decreased compared with patients exhibiting high CMTM3 expression (P=0.010). Cox multivariate analysis indicated that CMTM3 protein expression was an independent prognostic predictor for ESCC after resection. This study indicated that CMTM3 expression is significantly decreased in ESCC tissues and CMTM3 protein expression in resected tumors may present an effective prognostic biomarker.

The G protein-coupled estrogen receptor (GPER) is expressed in two different subcellular localizations reflecting distinct tumor properties in breast cancer.

PubMed

Samartzis, Eleftherios P; Noske, Aurelia; Meisel, Alexander; Varga, Zsuzsanna; Fink, Daniel; Imesch, Patrick

2014-01-01

The G protein-coupled estrogen receptor (GPER) is a novel estrogen receptor that mediates proliferative effects induced by estrogen but also by tamoxifen. The aim of our study was to analyze the frequency of GPER in a large collective of primary invasive breast carcinomas, with special emphasis on the subcellular expression and to evaluate the association with clinicopathological parameters and patient overall survival. The tissue microarrays from formalin-fixed, paraffin embedded samples of primary invasive breast carcinomas (n = 981) were analyzed for GPER expression using immunohistochemistry. Expression data were compared to the clinicopathological parameters and overall survival. GPER localization was also analyzed in two immortalized breast cancer cell lines T47D and MCF7 by confocal immunofluorescence microscopy. A predominantly cytoplasmic GPER expression was found in 189 carcinomas (19.3%), whereas a predominantly nuclear expression was observed in 529 cases (53.9%). A simultaneous comparable positive expression of both patterns was found in 32 of 981 cases (3.2%), and negative staining was detected in 295 cases (30%). Confocal microscopy confirmed the occurrence of cytoplasmic and nuclear GPER expression in T47D and MCF7. Cytoplasmic GPER expression was significantly associated with non-ductal histologic subtypes, low tumor stage, better histologic differentiation, as well as Luminal A and B subtypes. In contrast, nuclear GPER expression was significantly associated with poorly differentiated carcinomas and the triple-negative subtype. In univariate analysis, cytoplasmic GPER expression was associated with better overall survival (p = 0.012). Our data suggest that predominantly cytoplasmic and/or nuclear GPER expression are two distinct immunohistochemical patterns in breast carcinomas and may reflect different biological features, reason why these patterns should be clearly distinguished in histological evaluations. Prospective studies will be needed to assess whether the expression status of GPER in breast carcinomas should be routinely observed by clinicians, for instance, before implementing endocrine breast cancer treatment.

MAX Mutations in Endometrial Cancer: Clinicopathologic Associations and Recurrent MAX p.His28Arg Functional Characterization.

PubMed

Walker, Christopher J; Rush, Craig M; Dama, Paola; O'Hern, Matthew J; Cosgrove, Casey M; Gillespie, Jessica L; Zingarelli, Roman A; Smith, Blair; Stein, Maggie E; Mutch, David G; Shakya, Reena; Chang, Chia-Wen; Selvendiran, Karuppaiyah; Song, Jonathan W; Cohn, David E; Goodfellow, Paul J

2018-05-01

Genomic studies have revealed that multiple genes are mutated at varying frequency in endometrial cancer (EC); however, the relevance of many of these mutations is poorly understood. An EC-specific recurrent mutation in the MAX transcription factor p.His28Arg was recently discovered. We sought to assess the functional consequences of this hotspot mutation and determine its association with cancer-relevant phenotypes. MAX was sequenced in 509 endometrioid ECs, and associations between mutation status and clinicopathologic features were assessed. EC cell lines stably expressing MAXH28R were established and used for functional experiments. DNA binding was examined using electrophoretic mobility shift assays and chromatin immunoprecipitation. Transcriptional profiling was performed with microarrays. Murine flank (six to 11 mice per group) and intraperitoneal tumor models were used for in vivo studies. Vascularity of xenografts was assessed by MECA-32 immunohistochemistry. The paracrine pro-angiogenic nature of MAXH28R-expressing EC cells was tested using microfluidic HUVEC sprouting assays and VEGFA enzyme-linked immunosorbent assays. All statistical tests were two-sided. Twenty-two of 509 tumors harbored mutations in MAX, including 12 tumors with the p.His28Arg mutation. Patients with a MAX mutation had statistically significantly reduced recurrence-free survival (hazard ratio = 4.00, 95% confidence interval = 1.15 to 13.91, P = .03). MAXH28R increased affinity for canonical E-box sequences, and MAXH28R-expressing EC cells dramatically altered transcriptional profiles. MAXH28R-derived xenografts statistically significantly increased vascular area compared with MAXWT and empty vector tumors (P = .003 and P = .008, respectively). MAXH28R-expressing EC cells secreted nearly double the levels of VEGFA compared with MAXWT cells (P = .03, .005, and .005 at 24, 48, and 72 hours, respectively), and conditioned media from MAXH28R cells increased sprouting when applied to HUVECs. These data highlight the importance of MAX mutations in EC and point to increased vascularity as one mechanism contributing to clinical aggressiveness of EC.

The G Protein-Coupled Estrogen Receptor (GPER) Is Expressed in Two Different Subcellular Localizations Reflecting Distinct Tumor Properties in Breast Cancer

PubMed Central

Samartzis, Eleftherios P.; Noske, Aurelia; Meisel, Alexander; Varga, Zsuzsanna; Fink, Daniel; Imesch, Patrick

2014-01-01

Introduction The G protein-coupled estrogen receptor (GPER) is a novel estrogen receptor that mediates proliferative effects induced by estrogen but also by tamoxifen. The aim of our study was to analyze the frequency of GPER in a large collective of primary invasive breast carcinomas, with special emphasis on the subcellular expression and to evaluate the association with clinicopathological parameters and patient overall survival. Methods The tissue microarrays from formalin-fixed, paraffin embedded samples of primary invasive breast carcinomas (n = 981) were analyzed for GPER expression using immunohistochemistry. Expression data were compared to the clinicopathological parameters and overall survival. GPER localization was also analyzed in two immortalized breast cancer cell lines T47D and MCF7 by confocal immunofluorescence microscopy. Results A predominantly cytoplasmic GPER expression was found in 189 carcinomas (19.3%), whereas a predominantly nuclear expression was observed in 529 cases (53.9%). A simultaneous comparable positive expression of both patterns was found in 32 of 981 cases (3.2%), and negative staining was detected in 295 cases (30%). Confocal microscopy confirmed the occurrence of cytoplasmic and nuclear GPER expression in T47D and MCF7. Cytoplasmic GPER expression was significantly associated with non-ductal histologic subtypes, low tumor stage, better histologic differentiation, as well as Luminal A and B subtypes. In contrast, nuclear GPER expression was significantly associated with poorly differentiated carcinomas and the triple-negative subtype. In univariate analysis, cytoplasmic GPER expression was associated with better overall survival (p = 0.012). Conclusion Our data suggest that predominantly cytoplasmic and/or nuclear GPER expression are two distinct immunohistochemical patterns in breast carcinomas and may reflect different biological features, reason why these patterns should be clearly distinguished in histological evaluations. Prospective studies will be needed to assess whether the expression status of GPER in breast carcinomas should be routinely observed by clinicians, for instance, before implementing endocrine breast cancer treatment. PMID:24421881

Xp11 translocation renal cell carcinoma in adults: a clinicopathological and comparative genomic hybridization study

PubMed Central

Zou, Hong; Kang, Xueling; Pang, Li-Juan; Hu, Wenhao; Zhao, Jin; Qi, Yan; Hu, Jianming; Liu, Chunxia; Li, Hongan; Liang, Weihua; Yuan, Xianglin; Li, Feng

2014-01-01

To study the clinicopathological and genomic characteristics of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) in adults, we analyzed 9 Xp11.2 RCCs, confirmed by transcription factor E3 (TFE3) immunohistochemistry, in patients aged ≥20 years. TFE3 expression was also determined in 12 cases of alveolar soft part sarcoma (ASPS) served as a positive control. Comparative genomic hybridization (CGH) was used to investigate genomic imbalances in all Xp11.2 RCC cases. Most of our Xp11.2 RCC patients (5/9) presented with TNM stages 3-4, and 6 patients died 10 months to 7 years after their operation. Histologically, Xp11.2 RCC was composed of a mixed papillary nested/alveolar growth pattern (8/9). Immunostaining showed that all Xp11.2 RCC and ASPS cases had strong TFE3 expression and high positive ratios for p53 and vimentin. However, there were significant differences in the expression of AMACR (p<0.001), AE1/AE3 (p=0.002), and CD10 (p=0.024) between the 2 diseases. CGH profiles showed chromosomal imbalances in all 9 Xp11.2 RCC cases; gains were observed in chromosomes Xp11 (6/9), 7q20-25, 12q25-31 (5/9), 7p16-24 (4/9), 8p12-13, 8q20-21, 16q20-22, 17q25-26, 20q22-23 (4/9), and losses occurred frequently on chromosomes 3p12-16, 9q31-32, 14q22-24 (4/9). Our Conclusions show Xp11.2 RCC that occur in adults may be aggressive cancers, the expressions of AMACR, CD10, AE1/AE3 are helpful in the differential diagnosis between Xp11.2 RCC and ASPS, and CGH assay is a useful complementary method for confirming the diagnosis of Xp11.2 RCC. PMID:24427344

Risk of recurrence and chemotherapy benefit for patients with node-negative, estrogen receptor-positive breast cancer: recurrence score alone and integrated with pathologic and clinical factors.

PubMed

Tang, Gong; Cuzick, Jack; Costantino, Joseph P; Dowsett, Mitch; Forbes, John F; Crager, Michael; Mamounas, Eleftherios P; Shak, Steven; Wolmark, Norman

2011-11-20

The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.

Risk of Recurrence and Chemotherapy Benefit for Patients With Node-Negative, Estrogen Receptor–Positive Breast Cancer: Recurrence Score Alone and Integrated With Pathologic and Clinical Factors

PubMed Central

Tang, Gong; Cuzick, Jack; Costantino, Joseph P.; Dowsett, Mitch; Forbes, John F.; Crager, Michael; Mamounas, Eleftherios P.; Shak, Steven; Wolmark, Norman

2011-01-01

Purpose The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) –positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. Patients and Methods From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. Results RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). Conclusion RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit. PMID:22010013

Xp11 translocation renal cell carcinoma in adults: a clinicopathological and comparative genomic hybridization study.

PubMed

Zou, Hong; Kang, Xueling; Pang, Li-Juan; Hu, Wenhao; Zhao, Jin; Qi, Yan; Hu, Jianming; Liu, Chunxia; Li, Hongan; Liang, Weihua; Yuan, Xianglin; Li, Feng

2014-01-01

To study the clinicopathological and genomic characteristics of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) in adults, we analyzed 9 Xp11.2 RCCs, confirmed by transcription factor E3 (TFE3) immunohistochemistry, in patients aged ≥20 years. TFE3 expression was also determined in 12 cases of alveolar soft part sarcoma (ASPS) served as a positive control. Comparative genomic hybridization (CGH) was used to investigate genomic imbalances in all Xp11.2 RCC cases. Most of our Xp11.2 RCC patients (5/9) presented with TNM stages 3-4, and 6 patients died 10 months to 7 years after their operation. Histologically, Xp11.2 RCC was composed of a mixed papillary nested/alveolar growth pattern (8/9). Immunostaining showed that all Xp11.2 RCC and ASPS cases had strong TFE3 expression and high positive ratios for p53 and vimentin. However, there were significant differences in the expression of AMACR (p<0.001), AE1/AE3 (p=0.002), and CD10 (p=0.024) between the 2 diseases. CGH profiles showed chromosomal imbalances in all 9 Xp11.2 RCC cases; gains were observed in chromosomes Xp11 (6/9), 7q20-25, 12q25-31 (5/9), 7p16-24 (4/9), 8p12-13, 8q20-21, 16q20-22, 17q25-26, 20q22-23 (4/9), and losses occurred frequently on chromosomes 3p12-16, 9q31-32, 14q22-24 (4/9). Our Conclusions show Xp11.2 RCC that occur in adults may be aggressive cancers, the expressions of AMACR, CD10, AE1/AE3 are helpful in the differential diagnosis between Xp11.2 RCC and ASPS, and CGH assay is a useful complementary method for confirming the diagnosis of Xp11.2 RCC.

Duration of in vivo endotoxin tolerance in horses.

PubMed

Holcombe, Susan J; Jacobs, Carrie C; Cook, Vanessa L; Gandy, Jeffery C; Hauptman, Joseph G; Sordillo, Lorraine M

2016-05-01

Endotoxemia models are used to study mechanisms and treatments of early sepsis. Repeated endotoxin exposures induce periods of endotoxin tolerance, characterized by diminished proinflammatory responses to lipopolysaccharide (LPS) and modulated production of proinflammatory cytokines. Repeated measure designs using equine endotoxemia models are rarely performed, despite the advantages associated with reduced variability, because the altered responsiveness would confound study results and because the duration of equine endotoxin tolerance is unknown. We determined the interval of endotoxin tolerance, in vivo, in horses based on physical, clinicopathologic, and proinflammatory gene expression responses to repeated endotoxin exposures. Six horses received 30 ng/kg LPS in saline infused over 30 min. Behavior pain scores, physical examination parameters, and blood for complete blood count and proinflammatory gene expression were obtained at predetermined intervals for 24h. Horses received a total of 3 endotoxin exposures. The first exposure was LPS 1, followed 7 days later by LPS 7 or 14-21 days later by LPS 14-21. Lipopolysaccharide exposures were allocated in a randomized, crossover design. Lipopolysaccharide produced clinical and clinicopathologic signs of endotoxemia and increased expression of tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and IL-8, P<0.001. Horses exhibited evidence of endotoxin tolerance following LPS 7 but not following LPS 14-21. Horses had significantly lower pain scores, heart rates, respiratory rates and duration of fever, after LPS 7 compared to LPS 1 and LPS 14-21, P<0.001, and expression of TNFα was lower in the whole blood of horses after LPS 7, P=0.05. Clinical parameters and TNFα gene expression were similar or slightly increased in horses following LPS 14-21 compared to measurements made in horses following LPS 1, suggesting that endotoxin tolerance had subsided. A minimum of 3 weeks between experiments is warranted if repeated measures designs are used to assess in vivo response to endotoxin in horses. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation.

PubMed

Huang, Hsien-Neng; Chiang, Ying-Cheng; Cheng, Wen-Fang; Chen, Chi-An; Lin, Ming-Chieh; Kuo, Kuan-Ting

2015-02-01

Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (P<0.001), preserved ARID1A immunoreactivity (P=0.017) and infrequent PIK3CA mutation (P=0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age >45 (P=0.045) and preserved ARID1A expression (P=0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P=0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P=0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy.

Experience-based surgical approach to pancreatic mucinous cystic neoplasms with ovarian-type stroma

PubMed Central

Kang, Chang Moo; Matsushita, Akira; Hwang, Ho Kyoung; Matsuda, Yoko; Kim, Hyunki; Nakamura, Yoshiharu; Lee, Woo Jung

2018-01-01

The present study aimed to elucidate the clinicopathological characteristics of resected mucinous cystic neoplasm (MCN) with ovarian-type stroma and identify a surgical approach for MCN treatment, on the basis of Republic of Korean (Yonsei University College of Medicine, Seoul, South Korea) and Japanese (Nippon Medical School, Tokyo, Japan) bi-institutional collaboration. The present study retrospectively reviewed 55 MCNs with ovarian-type stroma using pathological re-examination. Clinicopathological features and preoperative clinical parameters were evaluated to predict malignant alterations in MCNs. The proportion of surgically treated MCNs has recently been increasing. All patients included in the present study were female, with a mean age of 47.9±13.3 years. Mural nodules were noted in 8 patients (14.5%) and the mean cyst size was 6.1±4.2 cm. A total of 9 patients (16.4%) were identified to exhibit non-invasive mucinous cystadenocarcinoma. The number of patients with small tumors (R2=−0.079, P=0.038) and asymptomatic pancreatic MCNs (P=0.022) was significantly increased (P<0.05), which resulted in the more frequent application of minimally invasive surgery (P<0.001). During the follow-up period (mean, 51.6 months; range, 1.1–242.8 months), no recurrence or tumor-associated mortality was identified. The presence of mural nodules (P=0.002) and a tumor size ≥4.5 cm (P=0.027) were identified as potential clinical parameters for predicting malignant transformation. The significance of mural nodules in predicting malignant transformation was increased in large MCNs (≥4.5 cm) of the pancreas compared with small MCNs (<4.5 cm) (P=0.002). Overall, non-invasive pancreatic MCNs are not aggressive, and minimally invasive pancreatectomy may be an effective approach for suitable patients. PMID:29434957

Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience.

PubMed

Gao, Yuping; Jiang, Jiyao; Liu, Qiang

2014-01-01

Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. β-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs.

Clinicopathological features of liver injury in patients with type 2 diabetes mellitus and comparative study of histologically proven nonalcoholic fatty liver diseases with or without type 2 diabetes mellitus.

PubMed

Shima, Toshihide; Uto, Hirofumi; Ueki, Kohjiro; Takamura, Toshinari; Kohgo, Yutaka; Kawata, Sumio; Yasui, Kohichiroh; Park, Hyohun; Nakamura, Naoto; Nakatou, Tatsuaki; Tanaka, Nobuyoshi; Umemura, Atsushi; Mizuno, Masayuki; Tanaka, Junko; Okanoue, Takeshi

2013-04-01

The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients. In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients. Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20-59 g and ≥60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy-two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM. Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/nonalcoholic steatohepatitis.

Association between baseline serum glucose, triglycerides and total cholesterol, and prostate cancer risk categories.

PubMed

Arthur, Rhonda; Møller, Henrik; Garmo, Hans; Holmberg, Lars; Stattin, Pår; Malmstrom, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Robinson, David; Jungner, Ingmar; Hemelrijck, Mieke Van

2016-06-01

Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA<4 μg/L, while those with glucose levels of 5.6-6.9 mmol/L had a greater odds of PSA>20 μg/L compared to PSA 4.0-9.9 μg/L. Hypertriglyceridemia was also positively associated with PSA>20 μg/L. Hyperglycemic men had a greater odds of intermediate- and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features.

PubMed

Hodges, Kurt B; Lopez-Beltran, Antonio; Davidson, Darrell D; Montironi, Rodolfo; Cheng, Liang

2010-02-01

The 2004 World Health Organization classification system for urothelial neoplasia classifies flat-related preneoplastic lesions as urothelial hyperplasia (flat and papillary), reactive urothelial atypia, urothelial atypia of unknown significance, urothelial dysplasia (low-grade intraurothelial neoplasia), and urothelial carcinoma in situ (high-grade intraurothelial neoplasia). Each lesion is defined with precise nomenclature and strict morphologic criteria. In many cases, morphologic features alone suffice for diagnosis. Other cases may require a panel of immunohistochemical antibodies consisting of cytokeratin 20, p53, and CD44 for diagnosis. Recent molecular studies have provided further insight into the premalignant potential of these urothelial lesions. Herein, we present a review of flat urothelial lesions of the urinary bladder as defined by the 2004 World Health Organization classification with focus on the clinicopathologic, immunohistochemical, and molecular features. Copyright 2010 Elsevier Inc. All rights reserved.

Robotic assisted gastrectomy compared with open resection: a case-matched study.

PubMed

Caruso, Riccardo; Vicente, Emilio; Quijano, Yolanda; Ielpo, Benedetto; Duran, Hipolito; Diaz, Eduardo; Fabra, Isabel; Ferri, Valentina

2018-05-04

In recent years, increasingly sophisticated tools have allowed for more complex robotic surgery. Robotic gastrectomy, however, is adopted in only a few selected centers. The goals of this study were to examine the adoption of robotic gastrectomy and to compare outcomes between open and robotic gastric resections. This is a case-matched analysis of patients who underwent robotic and open gastric resection performed at Sanchinarro University Hospital, Madrid from November 2011 to February 2017. Patient data were obtained retrospectively. Clinicopathologic characteristics and perioperative and postoperative outcomes were recorded and analyzed. Two groups of demographically similar patients were analyzed: the robotic group (n = 20) and the open surgery group (n = 19). The patient characteristics of the two groups have been compared. Robotic resection resulted in less blood loss, shorter postoperative hospital stay, and a longer operating time. The two groups had similar complication rates. Pathological data were similar for both procedures. Robotic gastrectomy for locally advanced gastric carcinoma is safe, and long-term outcomes are comparable to those patients who underwent open resection. Robotic gastrectomy resulted in a shorter hospital stay, less blood loss and morbidity comparable with the outcomes of open gastrectomy.

MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas.

PubMed

Huang, Wenting; Medeiros, L Jeffrey; Lin, Pei; Wang, Wei; Tang, Guilin; Khoury, Joseph; Konoplev, Sergej; Yin, C Cameron; Xu, Jie; Oki, Yasuhiro; Li, Shaoying

2018-05-21

High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p < 0.05). Induction chemotherapy used was similar for patients with triple hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.

High prevalence of luminal B breast cancer intrinsic subtype in Colombian women.

PubMed

Serrano-Gomez, Silvia Juliana; Sanabria-Salas, Maria Carolina; Hernández-Suarez, Gustavo; García, Oscar; Silva, Camilo; Romero, Alejandro; Mejía, Juan Carlos; Miele, Lucio; Fejerman, Laura; Zabaleta, Jovanny

2016-07-01

Breast cancer is the most frequent malignancy in women worldwide. Distinct intrinsic subtypes of breast cancer have different prognoses, and their relative prevalence varies significantly among ethnic groups. Little is known about the prevalence of breast cancer intrinsic subtypes and their association with clinicopathological data and genetic ancestry in Latin Americans. Immunohistochemistry surrogates from the 2013 St. Gallen International Expert Consensus were used to classify breast cancers in 301 patients from Colombia into intrinsic subtypes. We analyzed the distribution of subtypes by clinicopathological variables. Genetic ancestry was estimated from a panel of 80 ancestry informative markers. Luminal B breast cancer subtype was the most prevalent in our population (37.2%) followed by luminal A (26.3%), non-basal triple negative (NBTN) (11.6%), basal like (9%), human epidermal growth factor receptor 2 (HER2) enriched (8.6%) and unknown (7.3%). We found statistical significant differences in distribution between Colombian region (P = 0.007), age at diagnosis (P = 0.0139), grade (P < 0.001) and recurrence (P < 0.001) according to intrinsic subtype. Patients diagnosed with HER2-enriched, basal-like and NBTN breast cancer had the highest African ancestry. Future studies analyzing the molecular profiles of breast cancer in Colombian women will help us understand the molecular basis of this subtype distribution and compare the molecular characteristics of the different intrinsic subtypes in Colombian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of pico-tesla electromagnetic field treatment on wound healing in rats.

PubMed

Trostel, C Todd; McLaughlin, Ron M; Lamberth, John G; Cooper, Robert C; Elder, Steven H; Pool, Roy R; Gao, Cheng; Cromiak, Joseph A; Boyle, Carolyn R

2003-07-01

To evaluate the effects of a pico-tesla electromagnetic field (PTEF) on healing of sutured and open skin wounds and clinicopathologic variables in rats. 64 male Fischer-344 rats. An incision made in the dorsal aspect of the neck was sutured (n = 32) or left open to heal (32). In each group, 16 rats were not PTEF-treated (controls). Wound treatment consisted of exposure to a PTEF once daily. Rats in each group were euthanatized at days 2, 4, 7, and 14. Wounds were evaluated via tensiometry (sutured wounds), digital planimetry (open wounds), laser Doppler perfusion imaging, bacteriologic culture, and histologic examination. Blood samples were collected from all rats for analysis. At day 14, sutured wounds in PTEF-treated rats were stronger (ultimate stress) and tougher (strain energy) than were sutured wounds in control rats. Open wounds in PTEF-treated rats contracted more quickly at days 2 and 4 than did those in control rats. Compared with control wounds, histologic changes (indicative of improved healing) in sutured and open wounds in PTEF-treated rats were detected as early as day 4. Laser Doppler perfusion measurements, results of CBCs, serum biochemical analyses, and bacteriologic cultures were not different between groups. Exposure to the PTEF caused no adverse effects on clinicopathologic, histologic, or bacteriologic variables tested in this study. It appears that PTEF is a safe form of adjuvant treatment for wounds and improves strength of sutured wounds and speeds contraction of open wounds.

Treponema denticola chymotrypsin-like proteinase is present in early-stage mobile tongue squamous cell carcinoma and related to the clinicopathological features.

PubMed

Listyarifah, Dyah; Nieminen, Mikko T; Mäkinen, Laura K; Haglund, Caj; Grenier, Daniel; Häyry, Valtteri; Nordström, Dan; Hernandez, Marcela; Yucel-Lindberg, Tülay; Tervahartiala, Taina; Ainola, Mari; Sorsa, Timo; Hagström, Jaana

2018-05-10

Certain periodontopathogenic bacteria have been linked to cancers. Treponema denticola (Td) is associated with severe periodontitis. Chymotrypsin-like proteinase (CTLP), a major virulence factor of Td, can degrade various host proteins and peptides, and modulate inflammatory responses. However the role of Td in the tongue carcinogenesis remains unknown. This study aimed to investigate the presence of Td-CTLP in early-stage mobile tongue squamous cell carcinoma (MTSCC) and its relation to clinical and pathological characteristics. The immunopositivity of Td-CTLP was assessed in samples obtained from 60 MTSCC patients and associated with their clinicopathological data. Additionally, Td-CTLP expression was compared with immunoexpression of matrix metalloproteinases (MMP-8 and -9), toll-like receptors (TLR-2, -4, -7 and -9), c-Myc, Ki-67, Bmi-1, and Snail. Td-CTLP was present in 95% of MTSCC tumours of which many (40.4%) showed high immunopositivity. Td-CTLP positivity was significantly associated with invasion depth, tumour diameter, and the expression of TLR-7, TLR-9, and c-Myc. High Td-CTLP immunopositivity in patients under the age of 60 predicted early relapse. Our data indicate that Td and its CTLP are present in early-stage MTSCC carcinoma and may contribute to carcinogenesis, and therefore provide novel perspectives into intervention and therapeutic measures of MTSCC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Clinicopathological and prognostic significance of cyclooxygenase-2 expression in head and neck cancer: A meta-analysis

PubMed Central

Guo, Qiaojuan; Ren, Hui; Hu, Yanping; Xie, Tao

2016-01-01

Several studies have assessed the clinicopathological and prognostic value of cyclooxygenase-2 (COX-2) expression in patients with head and neck cancer (HNC), but their results remain controversial. To address this issue, a meta-analysis was carried out. A total of 29 studies involving 2430 patients were subjected to final analysis. Our results indicated that COX-2 expression was not statistically associated with advanced tumor stage (OR, 1.23; 95% CI, 0.98–1.55) but correlated with high risk of lymph node metastasis (OR, 1.28; 95% CI, 1.03–1.60) and advanced TNM stage (OR, 1.33; 95% CI, 1.06–1.66). Moreover, COX-2 expression had significant effect on poor OS (HR, 1.93; 95% CI, 1.29–2.90), RFS (HR, 2.02; 95% CI, 1.00–4.08) and DFS (HR, 5.14; 95% CI, 2.84–9.31). The results of subgroup analyses revealed that COX-2 expression was related with high possibility of lymph node metastasis in oral cancer (OR, 1.49; 95% CI, 1.01–2.20) and advanced TNM stage in oral cancer (OR, 1.58; 95% CI, 1.05–2.37) and no site-specific HNC (OR, 1.64; 95% CI, 1.02–2.62). However, subgroup analyses only showed a tendency without statistically significant association between COX-2 expression and survival. Significant heterogeneity was not found when analyzing clinicopathological data, but it appeared when considering survival data. No publication bias was detected in this study. This meta-analysis suggested that COX-2 expression could act as a prognostic factor for patients with HNC. PMID:27323811

Prognostic value and clinicopathological significance of serum- and tissue-based cytokeratin 18 express level in breast cancer: a meta-analysis.

PubMed

Yang, Jiangling; Gao, Sicheng; Xu, Jian; Zhu, Junfeng

2018-04-27

Cytokeratin 18 (CK18), a type I cytokeratin of the intermediate filament family, has been associated with the prognosis of cancer patients for decades. However, its exact role in predicting the clinical outcome of breast cancer remains controversial. To comprehensively investigated the prognostic value of CK18 in breast cancer, a systematically meta-analysis was conducted to explore the association between CK18 expression and overall survival. Literature collection was conducted by retrieving electronic databases Pubmed, Cochrane Library, Web of Science, EMBASE, and OVID completely (up to January 1, 2017). Nine relevant studies with 4857 cases assessing the relationship between CK18 high expression and the outcome of breast cancer patients were enrolled in our analysis. The results indicated that the high level of CK18 expression was significantly associated with overall survival of breast cancer patients via a specimen-depended manner. Reports which used serum to detect the expression of CK18 predicted a poor outcome of breast cancer (HR = 1.24, 95%CI: 1.11-1.38, P <0.0001), while studies which used tissue as specimen indicated a reverse result (HR = 0.71, 95%CI: 0.60-0.84, P <0.00001). Moreover, overexpression of CK18 was highly relevant to advanced clinicopathological parameters of breast cancer, such as progesterone receptor, human epidermal growth factor receptor-2, tumor size, tumor stage, nodal status, and tumor grade. Taken together, the present study demonstrated that CK18 might be served as a novel biomarker to predict clinicopathological features and the outcome of breast cancer. © 2018 The Author(s).

Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis.

PubMed

Zhuan-Sun, Yongxun; Huang, Fengting; Feng, Min; Zhao, Xinbao; Chen, Wenying; Zhu, Zhe; Zhang, Shineng

2017-01-01

Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. However, the clinicopathologic significance and prognostic value of PD-L1 in pancreatic cancer (PC) remains controversial. In this study, we conducted a meta-analysis to retrospectively evaluate the relationship between PD-L1 and PC. PubMed and other databases were searched for the clinical studies published up to March 21, 2017, to be included in the meta-analysis. Hazard ratios and their 95% CIs were calculated. Risk ratios (RRs) were extracted to assess the correlations between the clinicopathologic parameters and PD-L1 expression. Ten studies including 1,058 patients were included in the meta-analysis. The pooled results indicated that positive PD-L1 expression was correlated with a poor overall survival outcome in PC patients (hazard ratio =1.76, 95% CI: 1.43-2.17, P <0.00001). Interestingly, high PD-L1 expression was correlated with poor pathologic differentiation (RR =1.57, 95% CI: 1.25-1.98, P =0.0001) and neural invasion (RR =1.30, 95% CI: 1.03-1.64, P =0.03). However, there were no significant correlations between PD-L1 expression and other clinicopathologic characteristics. In summary, our meta-analysis implied that PD-L1 could serve as a negative predictor for the overall survival of PC patients, and high expression of PD-L1 was correlated with poor differentiation and neural invasion, indicating that anti-PD-L1 treatments should be evaluated in PC patients, especially in those who exhibit these two characteristics.

Prognostic value of PD-L1 overexpression for pancreatic cancer: evidence from a meta-analysis

PubMed Central

Feng, Min; Zhao, Xinbao; Chen, Wenying; Zhu, Zhe; Zhang, Shineng

2017-01-01

Programmed death-ligand 1 (PD-L1) is an immune checkpoint that is often activated in cancer and plays a pivotal role in the initiation and progression of cancer. However, the clinicopathologic significance and prognostic value of PD-L1 in pancreatic cancer (PC) remains controversial. In this study, we conducted a meta-analysis to retrospectively evaluate the relationship between PD-L1 and PC. PubMed and other databases were searched for the clinical studies published up to March 21, 2017, to be included in the meta-analysis. Hazard ratios and their 95% CIs were calculated. Risk ratios (RRs) were extracted to assess the correlations between the clinicopathologic parameters and PD-L1 expression. Ten studies including 1,058 patients were included in the meta-analysis. The pooled results indicated that positive PD-L1 expression was correlated with a poor overall survival outcome in PC patients (hazard ratio =1.76, 95% CI: 1.43–2.17, P<0.00001). Interestingly, high PD-L1 expression was correlated with poor pathologic differentiation (RR =1.57, 95% CI: 1.25–1.98, P=0.0001) and neural invasion (RR =1.30, 95% CI: 1.03–1.64, P=0.03). However, there were no significant correlations between PD-L1 expression and other clinicopathologic characteristics. In summary, our meta-analysis implied that PD-L1 could serve as a negative predictor for the overall survival of PC patients, and high expression of PD-L1 was correlated with poor differentiation and neural invasion, indicating that anti-PD-L1 treatments should be evaluated in PC patients, especially in those who exhibit these two characteristics. PMID:29081663

RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer.

PubMed

Wang, Rui; Hu, Haichuan; Pan, Yunjian; Li, Yuan; Ye, Ting; Li, Chenguang; Luo, Xiaoyang; Wang, Lei; Li, Hang; Zhang, Yang; Li, Fei; Lu, Yongming; Lu, Qiong; Xu, Jie; Garfield, David; Shen, Lei; Ji, Hongbin; Pao, William; Sun, Yihua; Chen, Haiquan

2012-12-10

The RET fusion gene has been recently described in a subset of non-small-cell lung cancers (NSCLCs). Because we have limited knowledge about these tumors, this study was aimed at determining the clinicopathologic characteristics of patients with NSCLC harboring the RET fusion gene. We examined the RET fusion gene in 936 patients with surgically resected NSCLC using a reverse transcriptase polymerase chain reaction (PCR) plus quantitative real-time PCR strategy, with validation using immunohistochemical and fluorescent in situ hybridization assays. A subset of 633 lung adenocarcinomas was also studied for EGFR, KRAS, HER2, and BRAF mutations, as well as ALK rearrangements. Patient characteristics, including age, sex, smoking history, stage, grade, International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of subtypes of lung adenocarcinoma, and relapse-free survival, were collected. Of 936 patients with NSCLC, the RET fusion gene was exclusively detected in 13 patients (11 of 633 patients with adenocarcinomas and two of 24 patients with adenosquamous cell carcinomas). Of the 13 patients, nine patients had KIF5B-RET, three patients had CCDC6-RET, and one patient had a novel NCOA4-RET fusion. Patients with lung adenocarcinomas with RET fusion gene had more poorly differentiated tumors (63.6%; P = .029 for RET v ALK, P = .007 for RET v EGFR), with a tendency to be younger (≤ 60 years; 72.7%) and never-smokers (81.8%) and to have solid subtype (63.6%) and a smaller tumor (≤ 3 cm) with N2 disease (54.4%). The median relapse-free survival was 20.9 months. RET fusion occurs in 1.4% of NSCLCs and 1.7% of lung adenocarcinomas and has identifiable clinicopathologic characteristics, warranting further clinical consideration and targeted therapy investigation.

BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis.

PubMed

Chen, Dong; Huang, Jun-Fu; Liu, Kai; Zhang, Li-Qun; Yang, Zhao; Chuai, Zheng-Ran; Wang, Yun-Xia; Shi, Da-Chuan; Huang, Qing; Fu, Wei-Ling

2014-01-01

Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC. We identified studies that examined the effect of BRAFV600E mutation on CRC within the PubMed, ISI Science Citation Index, and Embase databases. The effect of BRAFV600E on outcome parameters was estimated by odds ratios (ORs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model. 25 studies with a total of 11,955 CRC patients met inclusion criteria. The rate of BRAFV600 was 10.8% (1288/11955). The BRAFV600E mutation in CRC was associated with advanced TNM stage, poor differentiation, mucinous histology, microsatellite instability (MSI), CpG island methylator phenotype (CIMP). This mutation was also associated with female gender, older age, proximal colon, and mutL homolog 1 (MLH1) methylation. This meta-analysis demonstrated that BRAFV600E mutation was significantly correlated with adverse pathological features of CRC and distinct clinical characteristics. These data suggest that BRAFV600E mutation could be used to supplement standard clinical and pathological staging for the better management of individual CRC patients, and could be considered as a poor prognostic marker for CRC.

Clinico-pathological Correlation of Thyroid Nodule Ultrasound and Cytology Using the TIRADS and Bethesda Classifications.

PubMed

Singaporewalla, R M; Hwee, J; Lang, T U; Desai, V

2017-07-01

Clinico-pathological correlation of thyroid nodules is not routinely performed as until recently there was no objective classification system for reporting thyroid nodules on ultrasound. We compared the Thyroid Imaging Reporting and Data System (TIRADS) of classifying thyroid nodules on ultrasound with the findings on fine-needle aspiration cytology (FNAC) reported using the Bethesda System. A retrospective analysis of 100 consecutive cases over 1 year (Jan-Dec 2015) was performed comparing single-surgeon-performed bedside thyroid nodule ultrasound findings based on the TIRADS classification to the FNAC report based on the Bethesda Classification. TIRADS 1 (normal thyroid gland) and biopsy-proven malignancy referred by other clinicians were excluded. Benign-appearing nodules were reported as TIRADS 2 and 3. Indeterminate or suspected follicular lesions were reported as TIRADS 4, and malignant-appearing nodules were classified as TIRADS 5 during surgeon-performed bedside ultrasound. All the nodules were subjected to ultrasound-guided FNAC, and TIRADS findings were compared to Bethesda FNAC Classification. Of the 100 cases, 74 were considered benign or probably benign, 20 were suspicious for malignancy, and 6 were indeterminate on ultrasound. Overall concordance rate with FNAC was 83% with sensitivity and specificity of 70.6 and 90.4%, respectively. The negative predictive value was 93.8%. It is essential for clinicians performing bedside ultrasound thyroid and guided FNAC to document their sonographic impression of the nodule in an objective fashion using the TIRADS classification and correlate with the gold standard cytology to improve their learning curve and audit their results.

Neuroendocrine neoplasms of liver - A 5-year retrospective clinico-pathological study applying World Health Organization 2010 classification.

PubMed

Burad, Deepak Kalyansingh; Kodiatte, Thomas Alex; Rajeeb, Sayd Mohamed; Goel, Ashish; Eapen, Chundamannil Eapen; Ramakrishna, Banumathi

2016-10-28

To study the clinicopathological characteristics of neuroendocrine neoplasms (NEN) on liver samples and apply World Health Organization (WHO) 2010 grading of gastroenteropancreatic (GEP) NEN. Clinicopathological features of 79 cases of NEN of the liver diagnosed between January 2011 to December 2015 were analyzed. WHO 2010 classification of GEP NEN was applied and the tumors were graded as G1, G2 or G3. Two more categories, D1/2 (discordant 1/2) and D2/3 (discordant 2/3) were also applied. The D1/2 grade tumors had a mitotic count of G1 and Ki-67 index of G2. The D2/3 tumors had a mitotic count of G2 and Ki-67 index of G3. The follow up details which were available till the end of the study period (December 2015) were collected. Of the 79 tumors, 16 each were G1 and G2, and 18 were G3 tumors. Of the remaining 29 tumors, 13 were assigned to D1/2 and 16 were D2/3 grade. Male preponderance was noted in all tumors except for G2 neoplasms, which showed a slight female predilection. The median age at presentation was 47 years (range 10-82 years). The most common presentation was abdominal pain (81%). Pancreas (49%) was the most common site of primary followed by gastrointestinal tract (24.4%) and lungs (18%). Radiologically, 87% of the patients had multiple liver lesions. Histopathologically, necrosis was seen in only D2/3 and G3 tumors. Microvascular invasion was seen in all grades. Metastasis occurred in all grades of primary NEN and the grades of the metastatic tumors and their corresponding primary tumors were similar in 67% of the cases. Of the 79 patients, 36 had at least one follow up visit with a median duration of follow up of 8.5 mo (range: 1-50 mo). This study did not show any impact of the grade of tumor on the short term clinical outcome of these patients. Liver biopsy is an important tool for clinicopathological characterization and grading of NEN, especially when the primary is not identified. Eighty-seven percent of the patients had multifocal liver lesions irrespective of the WHO grade, indicating a higher stage of disease at presentation. Follow up duration was inadequate to derive any meaningful conclusion on long term outcome in our study patients.

Education, the Brain and Dementia: Neuroprotection or Compensation?

ERIC Educational Resources Information Center

Brayne, Carol; Ince, Paul G.; Keage, Hannah A. D.; McKeith, Ian G.; Matthews, Fiona E.; Polvikoski, Tuomo; Sulkava, Raimo

2010-01-01

The potential protective role of education for dementia is an area of major interest. Almost all older people have some pathology in their brain at death but have not necessarily died with dementia. We have explored these two observations in large population-based cohort studies (Epidemiological Clinicopathological Studies in Europe; EClipSE) in…

Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients.

PubMed

Kader, A Karim; Sun, Jielin; Isaacs, Sarah D; Wiley, Kathleen E; Yan, Guifang; Kim, Seong-Tae; Fedor, Helen; DeMarzo, Angelo M; Epstein, Jonathan I; Walsh, Patrick C; Partin, Alan W; Trock, Bruce; Zheng, S Lilly; Xu, Jianfeng; Isaacs, William

2009-08-01

More than a dozen single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk from genome-wide association studies (GWAS). Their association with PCa aggressiveness and clinicopathologic variables is inconclusive. Twenty PCa risk SNPs implicated in GWAS and fine mapping studies were evaluated in 5,895 PCa cases treated by radical prostatectomy at Johns Hopkins Hospital, where each tumor was uniformly graded and staged using the same protocol. For 18 of the 20 SNPs examined, no statistically significant differences (P > 0.05) were observed in risk allele frequencies between patients with more aggressive (Gleason scores > or =4 + 3, or stage > or =T3b, or N+) or less aggressive disease (Gleason scores < or =3 + 4, and stage < or =T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease rs2735839 in KLK3 (P = 8.4 x 10(-7)) and rs10993994 in MSMB (P = 0.046), the alleles that are associated with increased risk for PCa were more frequent in patients with less aggressive disease. Since these SNPs are known to be associated with PSA levels in men without PCa diagnoses, these latter associations may reflect the enrichment of low grade, low stage cases diagnosed by contemporary disease screening with PSA. The vast majority of PCa risk-associated SNPs are not associated with aggressiveness and clinicopathologic variables of PCa. Correspondingly, they have minimal utility in predicting the risk for developing more or less aggressive forms of PCa.

COX-2 Expression Correlates With Survival in Patients With Osteosarcoma Lung Metastases

PubMed Central

Rodriguez, Nidra I.; Hoots, William Keith; Koshkina, Nadezhda V.; Morales-Arias, Jaime A.; Arndt, Carola A.; Inwards, Carrie Y.; Hawkins, Douglas S.; Munsell, Mark F.; Kleinerman, Eugenie S.

2009-01-01

Summary The purpose of this study was to determine whether a correlation exists between tumor cyclooxygenase (COX)-2 expression and disease-specific survival in patients with osteosarcoma lung metastases. Thirty-six patients diagnosed with osteosarcoma lung metastases between the years 1990 and 2001 were included in this retrospective study. The majority of the patients (72%) presented newly -diagnosed osteosarcoma lung metastases whereas the remaining patients (28%) presented recurrent disease. Clinicopathologic parameters were obtained from patients’ clinical records. Tissue samples were obtained at the time of resection of the lung metastases and stained for COX-2 using immunohistochemistry. Samples were graded according to the intensity of COX-2 staining (grade 0: negative, grade 1: very weak, grade 2: weak, grade 3: moderate, and grade 4: strong). COX-2 staining was correlated with disease-specific survival and clinicopathologic parameters using the Jonckheere-Terpstra and the Kruskal-Wallis tests. All patients with grade 3 or 4 COX-2 expression died of osteosarcoma lung metastases. Ten percent of patients with grade 2 COX-2 expression and 29% of patients with grade 1 expression were alive and free of disease at the last follow-up. By contrast, 60% of the patients with grade 0 COX-2 expression were alive and free of disease at the last follow-up. No association between COX-2 expression and clinicopathologic parameters was found. However, COX-2 expression correlated inversely with disease-specific survival in patients with osteosarcoma lung metastases. Our data indicate that COX-2 expression in metastatic osteosarcoma may have prognostic significance. PMID:18797196

Individual and cumulative effect of prostate cancer risk-associated variants on clinicopathologic variables in 5,895 prostate cancer patients

PubMed Central

Kader, A. Karim; Sun, Jielin; Isaacs, Sarah D.; Wiley, Kathleen E.; Yan, Guifang; Kim, Seong-Tae; Fedor, Helen; DeMarzo, Angelo M.; Epstein, Jonathan I.; Walsh, Patrick C.; Partin, Alan W.; Trock, Bruce; Zheng, S. Lilly; Xu, Jianfeng; Isaacs, William

2009-01-01

Background More than a dozen single nucleotide polymorphisms (SNPs) have been associated with prostate cancer (PCa) risk from genome-wide association studies (GWAS). Their association with PCa aggressiveness and clinicopathologic variables is inconclusive. Methods Twenty PCa risk SNPs implicated in GWAS and fine mapping studies were evaluated in 5,895 PCa cases treated by radical prostatectomy at Johns Hopkins Hospital, where each tumor was uniformly graded and staged using the same protocol. Results For 18 of the 20 SNPs examined, no statistically significant differences (P > 0.05) were observed in risk allele frequencies between patients with more aggressive (Gleason Scores ≥ 4+3, or stage ≥ T3b, or N+) or less aggressive disease (Gleason Scores ≤ 3+4, and stage ≤ T2, and N0). For the two SNPs that had significant differences between more and less aggressive disease (rs2735839 in KLK3 (P = 8.4 × 10−7) and rs10993994 in MSMB (P = 0.046), the alleles that are associated with increased risk for PCa were more frequent in patients with less aggressive disease. Since these SNPs are known to be associated with PSA levels in men without PCa diagnoses, these latter associations may reflect the enrichment of low grade, low stage cases diagnosed by contemporary disease screening with PSA. Conclusions The vast majority of PCa risk-associated SNPs are not associated with aggressiveness and clinicopathologic variables of PCa. Correspondingly, they have minimal utility in predicting the risk for developing more or less aggressive forms of PCa. PMID:19434657

Histological varieties of Epstein-Barr virus-related lymph node lesion resembling autoimmune disease-like clinicopathological findings in middle-aged and elderly patients: a study of six cases.

PubMed

Kojima, Masaru; Sugiura, Isamu; Itoh, Hideaki; Shimizu, Kazuhiko; Murayama, Kayoko; Motoori, Tadashi; Shimano, Shunichi; Masawa, Nobuhide; Nakamura, Shigeo

2006-01-01

Six cases were studied to further clarify clinicopathological findings of Epstein-Barr virus (EBV)-related lymph node lesions showing autoimmune disease-like clinicopathological findings (EBVAID) in middle-aged and elderly patients. The patients, four males and two females, ranged in age from 53 to 74 years, with a median age of 62 years. Clinically, they were characterized by systemic lymphadenopathy, "B"symptoms, polyclonal hypergammaglobulinemia, elevated serum lactate dehydrogenase and a transient presence of various autoantibodies, as well as an infrequent presence of atypical lymphocytosis in peripheral blood. Two cases were associated with idiopathic thrombocytopenic purpura. The clinical course was self-limiting. Histologically, three patterns could be delineated: pattern A, follicular hyperplasia with pronounced arborizing vasculature in the expanded paracortex (n=3); pattern B, follicular hyperplasia with pronounced interfollicular B-immunoblastic/plasma cell proliferation (n=2); and pattern C, paracortical hyperplasia containing numerous large transformed lymphocytes (n=1). In situ hybridization demonstrated a varying number of EBV-infected lymphocytes in the germinal center and in the interfollicular area. Polymerase chain reaction analysis demonstrated that neither clonal rearrangement of T-cell receptor gamma-chain nor immunoglobulin heavy-chain rearrangement was detected in the three cases examined. Although EBVAID appears to be rare in middle-aged and older adults, EBVAID exhibits histological variations and should be added to the differential diagnosis of various atypical or malignant lymphoproliferative disorders, in particular autoimmune-disease-associated lymphadenopathy and angioimmunoblastic T-cell lymphoma with a hyperplastic germinal center in middle-aged and elderly patients.

Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment

PubMed Central

Hasumi, Katsuhiko; Sugiyama, Yuko; Sakamoto, Kimihiko; Akiyama, Futoshi

2013-01-01

Natural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial carcinomas arising from endometrial hyperplasia. Clinicopathologically 131 patients with endometrial carcinoma measuring ≤10 mm in diameter (“small endometrial carcinoma”) were studied to get useful information for early diagnosis, treatment, and histogenesis. The entire endometrium of surgically removed uterus was step-cut and examined. The patients were, on average, 5 years younger than the controls whose carcinomas measure >10 mm (P < 0.0001). Of the 131 patients, 20% were asymptomatic although only 5% of the controls were asymptomatic (P < 0.0001). Seventy-six percent had the carcinomas located in the upper third section of the uterine corpus. Macroscopically 44% of the tumors were flat and 56% were elevated. Incidence of nodal and ovarian metastases were <1%. Forty percent of “small endometrial carcinomas” were associated with endometrial hyperplasia and 60% were not. It is logical to believe that there are two pathways of endometrial carcinogenesis: carcinomas occurring from hyperplasia (40%) and carcinomas occurring from normal endometrium (60%). As hyperplasia-carcinoma sequence is not a main route, we cannot probably prevent carcinomas only by treatment of hyperplasia. Effort must be focused on detecting early de novo carcinomas. As most “small endometrial carcinomas” arise in the upper third of the corpus, careful endometrial sampling there is important for early detection. PMID:24403260

Clinicopathologic correlation of chorioretinitis sclopetaria.

PubMed

Dubovy, S R; Guyton, D L; Green, W R

1997-01-01

To report the clinicopathologic features in the eye of a patient who sustained a traumatic chorioretinal rupture from a gunshot wound to the orbit, chorioretinitis sclopetaria, with clinical follow up of more than 20 years. The patient was studied ophthalmoscopically and by fluorescein angiography after the trauma and was seen intermittently thereafter. The eyes were obtained postmortem; sections of the central portion of the right eye, including the macula and optic nerve head, and the inferior cap were examined by light microscopy. Histopathologic study of the right eye showed partial loss of the nerve fiber and ganglion cell layers in the macular area, temporal peripapillary and macular loss of the photoreceptors with hypertrophy and hyperplasia of the retinal pigment epithelium, an epiretinal membrane, and three defects in Bruch's membrane. Inferiorly, there was a 5-mm defect in choroid, Bruch's membrane, and retina. These structures were replaced by a loose and dense fibrous connective tissue. The sclera and a long posterior ciliary nerve remained intact. A thin fibrovascular tissue from the choroid extended into the subretinal space where it was covered by retinal pigment epithelium and thickened basement membrane in the posterior aspect of the inferior lesion. Marked hemiatrophy of the optic nerve was present. The clinicopathologic features of chorioretinitis sclopetaria include direct traumatic chorioretinal rupture followed by marked fibrovascular proliferation with variable replacement of choroid and retina with no retinal detachment. Posteriorly, indirect macular choroidal ruptures with hyperplasia and migration of the retinal pigment epithelium into the retina and choroid, epiretinal membrane formation, loss of photoreceptors, and marked hemiatrophy of the optic nerve were present.

[Fibrohistiocytic tumors of the skin: a heterogeneous group of superficially located mesenchymal neoplasms].

PubMed

Mentzel, T

2015-02-01

So-called fibrohistiocytic tumors of the skin comprise a heterogeneous spectrum of superficially located neoplasms that often show fibroblastic and/or myofibroblastic differentiation. In this review clinicopathologically important variants of dermatofibroma and dermatofibrosarcoma protuberans and their differential diagnoses are discussed in detail. In addition, the clinicopathological features of atypical fibroxanthoma, angiomatoid fibrous histiocytoma, plexiform fibrohistiocytic tumors and pleomorphic dermal sarcoma are presented. Entities that have to be considered in the differential diagnosis are also mentioned.

Factors affecting the occurrence, duration of hospitalization and final outcome in canine parvovirus infection.

PubMed

Iris Kalli; Leontides, Leonidas S; Mylonakis, Mathios E; Adamama-Moraitou, Katerina; Rallis, Timoleon; Koutinas, Alexander F

2010-10-01

The objectives of this matched case-control study in a veterinary teaching hospital were to investigate the influence of signalment and historical data on the odds of occurrence of canine parvovirus (CPV) enteritis and the potential usefulness of the clinical signs and clinicopathologic abnormalities recorded on admission as prognostic indicators of mean duration of hospitalization (DOH) and outcome of the disease. Ninety-four puppies with natural CPV enteritis and 188 age-matched controls were studied. The odds to develop CPV enteritis were higher in purebreds compared to mixed-breed puppies. Vomiting and depression at the time of admission were associated with a prolongation of DOH by 2 and 1.75 days, respectively. The lymphopenic and hypoalbuminemic dogs were hospitalized for 1.9 and 2.5 more days, respectively, compared to those without these abnormalities. The odds of non-survival were higher in those puppies with evidence of systemic inflammatory response syndrome (SIRS) at the time of admission. 2010 Elsevier Ltd. All rights reserved.

Multiple granular cell tumors with metachronous occurrence in tongue and vulva. Clinicopathological and immunohistochemical study

PubMed Central

Vera-Sirera, Beatriz; Zabala, Pablo; Aviño-Mira, Carlos; Vera-Sempere, Francisco J.

2014-01-01

Granular cell tumor (GCT) usually occurs as a single tumor, although sometimes multiple lesions can occur. In present report we analyze the clinicopathological and immunohistochemical features of a multiple GCT involving the tongue of a 14-year-old girl, with no other abnormalities, with a metachronous occurrence of a second GCT in vulva, after a period of 10 years. Both tumors revealed S-100, vimentin and CD57 positivity. In addition, over expression of calretinin was observed in tumor cells located in the vicinity of pseudoepitheliomatous hyperplasia (PEH) of the tongue. Tumor vasculature situated close to the PEH showed marked CD105 reactivity, data not described so far, suggesting an interaction between PEH cells and underlying stroma, since GCT completely lacks CD105 vessels. Our study emphasizes that patients with GCT, especially young patients, should be followed long-term, looking for multiple tumors or other abnormalities suggestive of a systemic syndrome, given the associations described in multiple GCT. PMID:25949003

Prognostic predictors of patients with carcinoma of the gastric cardia.

PubMed

Zhang, Ming; Li, Zhigao; Ma, Yan; Zhu, Guanyu; Zhang, Hongfeng; Xue, Yingwei

2012-05-01

This study gives insight into survival predictors and clinicopathological features of carcinoma of the gastric cardia. The study included 233 patients who underwent operation for carcinoma of the gastric cardia. Clinicopathological prognostic variables were evaluated as predictors of long-term survival by univariate and multivariate analysis. Cox regression was used for multivariate analysis and survival curves were drawn by the Kaplan- Meier method. Carcinoma of the gastric cardia was characterized by positive lymph node metastasis (77.3%), serosal invasion (83.3%) and more stage III or IV tumors (72.5%). Overall 5-year survival rate was 21.9% and median survival period was 24 months. The 5-year survival rate was influenced by tumor size, depth on invasion, lymph node metastasis, extent of lymph node dissection, disease stage, operation methods and resection margin. The absent of serosal invasion and lymph node metastasis, curative resection should be considered to be the favourable predictors of long-term survival of patients with carcinoma of the gastric cardia.

Clinicopathologic correlations in Alibert-type mycosis fungoides.

PubMed

Eng, A M; Blekys, I; Worobec, S M

1981-06-01

Five cases of mycosis fungoides of the Alibert type were studied by taking multiple biopsy specimens at different stages of the disease. Large hyperchromatic, slightly irregular mononuclear cells are the most frequent cells. Ultrastructurally, the cells were only slightly convoluted, had prominent heterochromatin banding at the nuclear membrane, and unremarkable cytoplasmic organelles. Highly convoluted cerebriform nucleated cells were few. Large regular vesicular histiocytes were prominent in the early stages. Ultrastructurally, the cells showed evenly distributed euchromatin. Epidermotrophism was equally as important as Pautrier's abscess as a hallmark of the disease. Stereologic techniques comparing the infiltrate with regard to size and convolution of cells in all stages of mycosis fungoides with infiltrates seen in a variety of benign dermatoses showed no statistically significant differences.

Outcomes of subsequent non-muscle-invasive bladder cancer treated with intravesical Bacillus Calmette-Guérin after radical nephroureterectomy for upper urinary tract urothelial carcinoma.

PubMed

Miyake, Makito; Tatsumi, Yoshihiro; Matsumoto, Hiroaki; Nagao, Kazuhiro; Matsuyama, Hideyasu; Inamoto, Teruo; Azuma, Haruhito; Yasumoto, Hiroaki; Shiina, Hiroaki; Fujimoto, Kiyohide

2018-05-01

To describe the clinicopathological characteristics and prognosis of subsequent non-muscle-invasive bladder cancer (NMIBC) after radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC), and particularly its response to intravesical Bacillus Calmette-Guérin (BCG). An observational study was conducted in 1463 patients with UTUC who had undergone RNU and in 1555 patients with primary NMIBC. Of the 1463 patients with UTUC, 256 (17%) subsequently developed NMIBC (UTUC-NMIBC group) and were available for the analysis. The clinicopathological background and outcomes, including intravesical recurrence-free survival and bladder progression-free survival, were compared between the patients with UTUC-NMIBC and the patients with primary NMIBC treated with intravesical BCG. Propensity score matching was performed to adjust for the potential differences in the backgrounds of the two groups. To validate the utility of the CUETO scoring model in the UTUC-NMIBC group, risk scores were calculated and compared with the published probabilities for recurrence and progression. Compared with the unadjusted primary NMIBC group (n = 352), the UTUC-NMIBC group (n = 75) were found to have a worse prognosis for intravesical recurrence and progression, before propensity score matching. After propensity score matching for potential confounding factors, however, a worse prognosis was observed only for intravesical recurrence. The validation test of the CUETO scoring model for the UTUC-NMIBC group showed a significant difference in the rate of intravesical recurrence and progression for the 0-4 and 5-6 score groups between the UTUC-NMIBC group and the CUETO risk table reference data. Compared with the primary NMIBC group, the UTUC-NMIBC group had a worse prognosis after intravesical BCG, especially with regard to intravesical recurrence. This suggests that patients with UTUC-NMIBC are inherently poor responders to BCG exposure. An optimal treatment strategy and risk scoring model to select patients for adjuvant intravesical BCG, chemotherapy or immediate radical cystectomy should be established. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

The significance of granzyme B expression in patients with angiocentric lymphoma of the head and neck.

PubMed

Kim, G E; Yang, W I; Lee , S; Kim, Y B; Suh, C O; Yoon, J H; Oh, Y T; Chung, H C; Kim, B S

2001-06-15

The objectives of this study were to establish a correlation between granzyme B expression and the clinicopathologic characteristics of patients with angiocentric lymphomas of the head and neck and to determine whether the expression of granzyme B had any influence on the treatment outcomes of such patients. Fifty-seven patients with angiocentric lymphoma of the head and neck who were treated between 1987 and 1996 were divided into two groups according to whether their tumors were immunoreactive for granzyme B: the granzyme B negative group (n = 22 patients) and the granzyme B positive group (n = 35 patients). The clinicopathologic features, immunohistochemical findings, patterns of disease failure, and survival data for the granzyme B positive group were compared with those for the granzyme B negative group. Greater than 60% of patients with angiocentric lymphoma of the head and neck were shown to have granzyme B positive tumors. All tumors that expressed granzyme B also consistently coexpressed CD56, indicating that they probably are the neoplastic equivalent of either natural killer (NK) cells or activated cytotoxic T cells. Although there were no significant differences in histopathologic features or expression of CD45RO and polyclonal CD3-epsilon between the groups, the Epstein-Barr virus genomes were detected more frequently in the granzyme B positive group compared with the granzyme B negative group. Despite a similar rate of complete remission after initial treatment, the locoregional recurrence rate of patients in the granzyme B positive group was much higher compared with patients in the granzyme B negative group. In addition, compared with patients in the granzyme B negative group, patients in the granzyme B positive group also had an increased risk of systemic disease recurrence and a decreased overall survival rate. The data indicate that the cytotoxic granule-associated protein, granzyme B, may be used as an additional marker for identifying NK/T-cell lymphoma and as a prognostic indicator for risk assessment in patients with angiocentric lymphoma of the head and neck. Copyright 2001 American Cancer Society.

Intratumoral concentration of estrogens and clinicopathological changes in ductal carcinoma in situ following aromatase inhibitor letrozole treatment

PubMed Central

Takagi, K; Ishida, T; Miki, Y; Hirakawa, H; Kakugawa, Y; Amano, G; Ebata, A; Mori, N; Nakamura, Y; Watanabe, M; Amari, M; Ohuchi, N; Sasano, H; Suzuki, T

2013-01-01

Background: Estrogens have important roles in ductal carcinoma in situ (DCIS) of the breast. However, the significance of presurgical aromatase inhibitor treatment remains unclear. Therefore, we examined intratumoral concentration of estrogens and changes of clinicopathological factors in DCIS after letrozole treatment. Methods: Ten cases of postmenopausal oestrogen receptor (ER)-positive DCIS were examined. They received oral letrozole before the surgery, and the tumour size was evaluated by ultrasonography. Surgical specimens and corresponding biopsy samples were used for immunohistochemistry. Snap-frozen specimens were also available in a subset of cases, and used for hormone assays and microarray analysis. Results: Intratumoral oestrogen levels were significantly lower in DCIS treated with letrozole compared with that in those without the therapy. A great majority of oestrogen-induced genes showed low expression levels in DCIS treated with letrozole by microarray analysis. Moreover, letrozole treatment reduced the greatest dimension of DCIS, and significantly decreased Ki-67 and progesterone receptor immunoreactivity in DCIS tissues. Conclusion: These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens. PMID:23756858

Men and women show similar survival outcome in stage IV breast cancer.

PubMed

Wu, San-Gang; Zhang, Wen-Wen; Liao, Xu-Lin; Sun, Jia-Yuan; Li, Feng-Yan; Su, Jing-Jun; He, Zhen-Yu

2017-08-01

To evaluate the clinicopathological features, patterns of distant metastases, and survival outcome between stage IV male breast cancer (MBC) and female breast cancer (FBC). Patients diagnosed with stage IV MBC and FBC between 2010 and 2013 were included using the Surveillance, Epidemiology, and End Results program. Univariate and multivariate Cox regression analyses were used to analyze risk factors for overall survival (OS). A total of 4997 patients were identified, including 60 MBC and 4937 FBC. Compared with FBC, patients with MBC were associated with a significantly higher rate of estrogen receptor-positive, progesterone receptor-positive, unmarried, lung metastases, and a lower frequency of liver metastases. Univariate and multivariate analyses showed no significant difference in OS between MBC and FBC. In the propensity score-matched population, there was also no difference in survival between MBC and FBC. Multivariate analysis of MBC showed that OS was longer for patients aged 50-69 years and with estrogen receptor-positive disease. There was no significant difference in survival outcome between stage IV MBC and FBC, but significant differences in clinicopathological features and patterns of metastases between the genders. Copyright © 2017 Elsevier Ltd. All rights reserved.

Keratocystic odontogenic tumors related to Gorlin–Goltz syndrome: A clinicopathological study

PubMed Central

Khaliq, Mohammed Israr Ul; Shah, Ajaz A.; Ahmad, Irshad; Hasan, Shahid; Jangam, Sagar S.; Farah; Anwar

2015-01-01

Background Assess clinicopathological features of patients with keratocystic odontogenic tumor (KCOT) associated with Gorlin–Goltz syndrome in our institution from 2004 to 2015. Method After histopathological analyses of KCOT related to Gorlin–Goltz syndrome, 7 patients were assessed. These patients presented a total of 15 primary and 2 recurrent KCOT. Results All patients presented a multiple KCOT, and 13 lesions were located in mandible (77%) and 4 (23%) in maxilla. Most of the tumors presented a unilocular pattern (71%) and had tooth association (88%). Four patients (57%) were in the age group of 10–19 years and three patients (43%) were in the age group of 20–29 years. There were four male and three female patients. Conclusion KCOT is a frequent manifestation of Gorlin–Goltz syndrome and can be its first sign, mainly in young patients. The four patients presented with two lesions (57%) and three lesions in three patients (43%). PMID:27195205

Keratocystic odontogenic tumors related to Gorlin-Goltz syndrome: A clinicopathological study.

PubMed

Khaliq, Mohammed Israr Ul; Shah, Ajaz A; Ahmad, Irshad; Hasan, Shahid; Jangam, Sagar S; Farah; Anwar

2016-01-01

Assess clinicopathological features of patients with keratocystic odontogenic tumor (KCOT) associated with Gorlin-Goltz syndrome in our institution from 2004 to 2015. After histopathological analyses of KCOT related to Gorlin-Goltz syndrome, 7 patients were assessed. These patients presented a total of 15 primary and 2 recurrent KCOT. All patients presented a multiple KCOT, and 13 lesions were located in mandible (77%) and 4 (23%) in maxilla. Most of the tumors presented a unilocular pattern (71%) and had tooth association (88%). Four patients (57%) were in the age group of 10-19 years and three patients (43%) were in the age group of 20-29 years. There were four male and three female patients. KCOT is a frequent manifestation of Gorlin-Goltz syndrome and can be its first sign, mainly in young patients. The four patients presented with two lesions (57%) and three lesions in three patients (43%).

Clinicopathological analysis in PTCL-NOS with CADM1 expression.

PubMed

Kato, Takeharu; Miyoshi, Hiroaki; Kobayashi, Seiichiro; Yoshida, Noriaki; Imaizumi, Yoshitaka; Seto, Masao; Uchimaru, Kaoru; Miyazaki, Yasushi; Ohshima, Koichi

2017-11-01

Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), is a heterogeneous disease with respect to clinicopathological features. Cell adhesion molecule 1 (CADM1) has been reported to be ectopically expressed in adult T cell leukaemia/lymphoma (ATLL). However, the frequency of CADM1 expression remains unknown in peripheral T cell lymphomas. In the current study, CADM1 expression was analysed in 88 PTCL-NOS patients. CADM1 was expressed in 14 of 88 (15.9%) PTCL-NOS cases, and its expression was associated with C-C chemokine receptor type 4 (CCR4) expression and nuclear atypia. CADM1-positive PTCL-NOS cases (10/74) had a significantly poorer prognosis than CADM1-negative cases (64/74) (P = 0.001). Multivariate analysis confirmed that CADM1 expression was an independent prognostic factor in PTCL-NOS. These findings suggest that CADM1 expression is a novel prognostic factor for PTCL-NOS.

Increased expression of Rab coupling protein in squamous cell carcinoma of the head and neck and its clinical significance

PubMed Central

DAI, YAOZHANG; LIU, YONG; HUANG, DONGHAI; YU, CHANGYUN; CAI, GENGMING; PI, LEIMING; REN, CAIPING; CHEN, GEORGIA Z.; TIAN, YONGQUAN; ZHANG, XIN

2012-01-01

The role of Rab coupling protein (RCP) has not been previously investigated in squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to explore RCP protein expression and its clinicopathological significance in SCCHN. RCP protein expression in 95 SCCHN samples, 18 vocal nodule epithelia and 16 leukoplakia epithelia samples was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Our data indicated that vocal nodule epithelia, leukoplakia epithelia and SCCHN showed a gradual increase in the expression of RCP protein. RCP overexpression was significantly associated with T classification, clinical staging, lymph node metastasis and recurrence. Survival analysis revealed that a high RCP expression was significantly correlated with shorter overall survival and disease-free survival. In conclusion, RCP protein may contribute to the malignant progression of SCCHN, and serves as a novel prognostic marker in patients with SCCHN. PMID:22783424

Increased expression of Rab coupling protein in squamous cell carcinoma of the head and neck and its clinical significance.

PubMed

Dai, Yaozhang; Liu, Yong; Huang, Donghai; Yu, Changyun; Cai, Gengming; Pi, Leiming; Ren, Caiping; Chen, Georgia Z; Tian, Yongquan; Zhang, Xin

2012-06-01

The role of Rab coupling protein (RCP) has not been previously investigated in squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to explore RCP protein expression and its clinicopathological significance in SCCHN. RCP protein expression in 95 SCCHN samples, 18 vocal nodule epithelia and 16 leukoplakia epithelia samples was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Our data indicated that vocal nodule epithelia, leukoplakia epithelia and SCCHN showed a gradual increase in the expression of RCP protein. RCP overexpression was significantly associated with T classification, clinical staging, lymph node metastasis and recurrence. Survival analysis revealed that a high RCP expression was significantly correlated with shorter overall survival and disease-free survival. In conclusion, RCP protein may contribute to the malignant progression of SCCHN, and serves as a novel prognostic marker in patients with SCCHN.

Periosteal ganglion: a report of three new cases including MRI findings and a review of the literature.

PubMed

Okada, K; Unoki, E; Kubota, H; Abe, E; Taniwaki, M; Morita, M; Sato, K

1996-02-01

To clarify the clinicopathological features of periosteal ganglion. Three patients with periosteal ganglion were studied clinicopathologically. One patient was selected from the files of our institute and two from a consultation file. All three lesions were located over the medial aspect of the tibia. Plain radiographs showed cortical erosions of varying degrees and mild periosteal reaction of the medial side of the tibia. MR images demonstrated well-circumscribed lesions overlying the cortical bone of the tibia, shown as low-intensity areas on T1-weighted images. On T2-weighted images, lesions were homogeneous, lobulated, and showed a characteristic markedly increased signal intensity. These findings are helpful in making a diagnosis of periosteal ganglion. Each patient had an uneventful clinical course after an excision involving the wall of the ganglion, the adjoining periosteum, and the underlying sclerotic cortical bone.

Craniopharyngioma: a clinicopathological study of 141 cases.

PubMed

Tavangar, Seyed Mohammad; Larijani, Bagher; Mahta, Ali; Hosseini, Seyed Mehdi Abdolahzadeh; Mehrazine, Masoud; Bandarian, Fatemeh

2004-01-01

Craniopharyngioma is a tumor of the suprasellar region that histologically has two distinct variants with some differences in clinical behavior. The papillary type is almost always seen in adults and has a more indolent course compared with the adamantinomatous type, which is more common in childhood. In the present study, surgical specimens of craniopharyngiomas from 141 patients were reviewed. Their histomorphologic types were determined and the clinical features and prognosis of each group were assessed. The sizes of papillary type tumors were smaller and during the follow-up period there was no recurrence in the squamous papillary group. Aside from surgical resection (total vs subtotal), the recurrence rate for papillary type craniopharyngioma was lower than for adamantinomatous type. Histologic typing of craniopharyngioma especially in adults is useful for decision making with regard to treatment and follow-up.

Oral lymphoepithelial cyst: A clinicopathological study of 26 cases and review of the literature.

PubMed

Sykara, Maria; Ntovas, Panagiotis; Kalogirou, Eleni-Marina; Tosios, Konstantinos I; Sklavounou, Alexandra

2017-08-01

Τo describe the clinicopathological features of 26 oral lymphoepithelial cysts (LECs) and review the literature. Twenty-six cases of oral LECs diagnosed during a 37-year period were retrospectively collected. The patients' gender and age, as well as the main clinical features of the cysts were retrieved from the requisition forms. The main microscopic features were recorded after reevaluation of all cases. Pubmed and Google Scholar electronic databases were searched with the key word "oral LEC". Inclusion criteria were the microscopic confirmation of LEC diagnosis and the report at least two of three main clinical features (gender, age and cyst's location). The 26 oral LECs represented 0.08% of 31,564 biopsies accessioned during the study period. They affected 25 patients, 14 females and 11 males with a mean age of 33.04±9.81 years. They appeared as smooth (92%) nodules, with soft (24%) or firm (76%) consistency and normal (28%), yellow to normal (20%), yellow (32%) or white (20%) hue, in the tongue (69.23%) or the floor of mouth (30.77%). They were covered by parakeratinized squamous (92.31%) or non-keratinized (7.69%) epithelium and contained desquamated epithelial cells, amorphous eosinophilic material and/or inflammatory cells (100%). The lymphoid tissue surrounded the cystic cavity partially (34.62%) or completely (65.38%), often in a follicular pattern with prominent germinal centers (53.85%). Literature review yielded 316 cases of oral LECs derived from 25 case reports, 3 case studies/retrospective studies with detailed information for each case and 7 studies with summarized data. Oral LEC is a pathologic entity with discrete clinical presentation that is, however, commonly misdiagnosed in clinical practice as other, mostly benign, entities. Its pathogenesis remains obscure, as its clinicopathologic features are consistent with both theories suggested up to date. Key words: Oral lymphoepithelial cyst; developmental cyst; non odontogenic cyst; lymphoid tissue; oral tonsil.

Oral lymphoepithelial cyst: A clinicopathological study of 26 cases and review of the literature

PubMed Central

Sykara, Maria; Ntovas, Panagiotis; Tosios, Konstantinos I.; Sklavounou, Alexandra

2017-01-01

Introduction Τo describe the clinicopathological features of 26 oral lymphoepithelial cysts (LECs) and review the literature. Material and Methods Twenty-six cases of oral LECs diagnosed during a 37-year period were retrospectively collected. The patients’ gender and age, as well as the main clinical features of the cysts were retrieved from the requisition forms. The main microscopic features were recorded after reevaluation of all cases. Pubmed and Google Scholar electronic databases were searched with the key word “oral LEC”. Inclusion criteria were the microscopic confirmation of LEC diagnosis and the report at least two of three main clinical features (gender, age and cyst’s location). Results The 26 oral LECs represented 0.08% of 31,564 biopsies accessioned during the study period. They affected 25 patients, 14 females and 11 males with a mean age of 33.04±9.81 years. They appeared as smooth (92%) nodules, with soft (24%) or firm (76%) consistency and normal (28%), yellow to normal (20%), yellow (32%) or white (20%) hue, in the tongue (69.23%) or the floor of mouth (30.77%). They were covered by parakeratinized squamous (92.31%) or non-keratinized (7.69%) epithelium and contained desquamated epithelial cells, amorphous eosinophilic material and/or inflammatory cells (100%). The lymphoid tissue surrounded the cystic cavity partially (34.62%) or completely (65.38%), often in a follicular pattern with prominent germinal centers (53.85%). Literature review yielded 316 cases of oral LECs derived from 25 case reports, 3 case studies/retrospective studies with detailed information for each case and 7 studies with summarized data. Conclusions Oral LEC is a pathologic entity with discrete clinical presentation that is, however, commonly misdiagnosed in clinical practice as other, mostly benign, entities. Its pathogenesis remains obscure, as its clinicopathologic features are consistent with both theories suggested up to date. Key words:Oral lymphoepithelial cyst; developmental cyst; non odontogenic cyst; lymphoid tissue; oral tonsil. PMID:28936296

[Correlation between typing of peripheral neuroblastic tumors and prognosis: a clinicopathologic study of 135 cases].

PubMed

YIN, Min-zhi; ZHANG, Zhong-de; MA, Jing; SHEN, Ping; CHEN, Jie-feng; ZHANG, Hui-zhen

2011-03-01

To study the clinicopathologic characteristics of peripheral neuroblastic tumors and to investigate the prognostic significance of International Neuroblastoma Pathology Classification (INPC). One hundred and thirty-five cases of peripheral neuroblastic tumors encountered in Shanghai Children's Medical Center were enrolled into the study. All the cases were classified according to INPC and International Neuroblastoma Staging System (INSS). The follow-up data were analyzed. The consensus diagnoses of the 135 cases were as follows: 80 cases (59.2%) of neuroblastoma, 24 cases (17.8%) of ganglioneuroblastoma, intermixed, 17 cases (12.6%) of ganglioneuroma and 14 cases (10.4%) of ganglioneuroblastoma, nodular. The cases were subdivided into 2 subgroups: favorable histology (number = 90, 66.7%) and unfavorable histology (number = 45, 33.3%). According to INSS, the number of cases in stages I, II, III and IV was 22 (16.3%), 24 (17.8%), 34 (25.2%) and 55 (40.7%), respectively. The survival of peripheral neuroblastic tumors correlated with histologic diagnosis, INPC and INSS (P < 0.05). Diagnostic categorization of peripheral neuroblastic tumors according to INPC is of prognostic value.

Clinicopathological factors relating malignant lymphoma with Sjögren's syndrome.

PubMed

Anaya, J M; McGuff, H S; Banks, P M; Talal, N

1996-04-01

This study was undertaken to summarize the current status of the clinicopathologic factors related to non-Hodgkin's lymphoma (NHL) development in patients with Sjögren's syndrome (SS). Through a MEDLINE search, pertinent articles on SS, monoclonality, and NHL were found and reviewed. Malignant lymphoma description was based on the International Lymphoma Study Group classification. Patients with SS are known to have an increased risk for developing B-cell NHL (B-NHL). However, such a complication occurs in less than 10% of patients, being reported mainly in those with primary SS. Extranodal low-grade B-NHL are observed most frequently. Persistent enlargement of parotid glands, adenopathy, monoclonal gammopathy, and cross-reactive idiotypes are all signs suggesting possible lymphoma evolution. Although monoclonality does not mean malignancy unequivocally, it is considered to be a precursor for NHL development in SS. Factors implicated into lymphomagenesis in SS include dysregulation in the mechanisms leading to apoptosis, hyperstimulation of B-1 cells, and an infectious agent. Polyclonal lymphoproliferation characterizing SS might in some instances transform into monoclonal, and then to malignancy. Further studies on the mechanism whereby NHL develops in SS are warranted.

Poisoning and Intoxication by Trace Elements in Children. An Abstract Review of the Worldwide Medical Literature 1966-1971.

ERIC Educational Resources Information Center

Public Health Service (DHEW), Washington, DC. Bureau of Community Environmental Management.

This annotated bibliography of 247 entries is divided into the following categories: (a) general aspects and reviews; (b) sources of poisoning, epidemiology, and pica studies; (c) clinico-pathological studies; (d) diagnosis and screening; (e) laboratory methods; and (f) treatment and prevention. A subject and author index is included. (PD)

A large, single-center, real-world study of clinicopathological characteristics and treatment in advanced ALK-positive non-small-cell lung cancer.

PubMed

Chen, Gang; Chen, Xi; Zhang, Yaxiong; Yan, Fang; Fang, Wenfeng; Yang, Yunpeng; Hong, Shaodong; Miao, Siyu; Wu, Manli; Huang, Xiaodan; Luo, Youli; Zhou, Cong; Gong, Run; Huang, Yan; Zhou, Ningning; Zhao, Hongyun; Zhang, Li

2017-05-01

Crizotinib has achieved astonishing success in advanced non-small-cell lung cancer (NSCLC) patients harboring anaplastic lymphoma kinase (ALK) rearrangement. However, no real-world studies described the clinicopathological characteristics and treatment of such patients in China. Patients were consecutively collected from Sun Yat-sen University Cancer Center. Chi-square test was applied to explore the relationship between ALK fusion status and metastasis sites. Kaplan-Meier methods and multivariable analyses were used to estimate progression-free survival (PFS). A total of 291 advanced NSCLC patients (ALK (+), N = 97; both ALK & epidermal growth factor receptor (EGFR) (-), N = 194) were enrolled. The occurrence of brain metastasis in ALK-positive patients was significantly higher than double-negative ones both at baseline (26.5% vs. 16.5%, P = 0.038) and during treatment (25.8% vs. 11.9%, P = 0.003), but opposite for pleural effusion (6.2% vs. 26.9%, P < 0.001 at baseline; 3.1% vs. 10.3%, P = 0.031 during treatment). ALK-positive patients of 53.6% used crizotinib, whereas others only received chemotherapy (37.1%) or supportive care (9.3%). Usage of crizotinib prolonged PFS compared with chemotherapy in ALK-positive patients (median PFS 17.6 m vs. 4.8 m, P < 0.001). ALK-positive NSCLC had more brain metastasis and less pleural effusion than double-negative ones. Crizotinib showed better PFS than chemotherapy in advanced ALK-positive NSCLC at any line. However, half advanced ALK-positive patients never received crizotinib, which was grim and need improving. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Renal Amyloidosis: Origin and Clinicopathologic Correlations of 474 Recent Cases

PubMed Central

Said, Samar M.; Sethi, Sanjeev; Valeri, Anthony M.; Leung, Nelson; Cornell, Lynn D.; Fidler, Mary E.; Herrera Hernandez, Loren; Vrana, Julie A.; Theis, Jason D.; Quint, Patrick S.; Dogan, Ahmet

2013-01-01

Summary Background and objectives The kidney is the organ most commonly involved in systemic amyloidosis. This study reports the largest clinicopathologic series of renal amyloidosis. Design, setting, participants, & measurements This study provides characteristics of 474 renal amyloidosis cases evaluated at the Mayo Clinic Renal Pathology Laboratory from 2007 to 2011, including age, sex, serum creatinine, proteinuria, type of amyloid, and tissue distribution according to type. Results The type of amyloid was Ig amyloidosis in 407 patients (85.9%), AA amyloidosis in 33 (7.0%), leukocyte chemotactic factor 2 amyloidosis in 13 (2.7%), fibrinogen A α chain amyloidosis in 6 (1.3%), Apo AI, Apo AII, or Apo AIV amyloidosis in 3 (0.6%), combined AA amyloidosis/Ig heavy and light chain amyloidosis in 1 (0.2%), and unclassified in 11 (2.3%). Laser microdissection/mass spectrometry, performed in 147 cases, was needed to determine the origin of amyloid in 74 of the 474 cases (16%), whereas immunofluorescence failed to diagnose 28 of 384 light chain amyloidosis cases (7.3%). Leukocyte chemotactic factor 2 amyloidosis and Apo AI, Apo AII, or Apo AIV amyloidosis were characterized by diffuse interstitial deposition, whereas fibrinogen A α chain amyloidosis showed obliterative glomerular involvement. Compared with other types, Ig amyloidosis was associated with lower serum creatinine, higher degree of proteinuria, and amyloid spicules. Conclusions In the authors’ experience, the vast majority of renal amyloidosis cases are Ig derived. The newly identified leukocyte chemotactic factor 2 amyloidosis form was the most common of the rarer causes of renal amyloidosis. With the advent of laser microdissection/mass spectrometry for amyloid typing, the origin of renal amyloidosis can be determined in >97% of cases. PMID:23704299

The role of leptin in gastric cancer: Clinicopathologic features and molecular mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Kang Nyeong; Choi, Ho Soon, E-mail: hschoi96@hanyang.ac.kr; Yang, Sun Young

Highlights: • Leptin and Ob-R are expressed in gastric adenoma and early and advanced cancer. • Leptin is more likely associated with differentiated gastric cancer or cardia cancer. • Leptin proliferates gastric cancer cells via activating the STAT3 and ERK1/2 pathways. - Abstract: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastricmore » adenoma (n = 38), early gastric cancer (EGC) (n = 38), and advanced gastric cancer (AGC) (n = 38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.« less

Clinical significance of preoperative serum albumin level for prognosis in surgically resected patients with non-small cell lung cancer: Comparative study of normal lung, emphysema, and pulmonary fibrosis.

PubMed

Miura, Kentaro; Hamanaka, Kazutoshi; Koizumi, Tomonobu; Kitaguchi, Yoshiaki; Terada, Yukihiro; Nakamura, Daisuke; Kumeda, Hirotaka; Agatsuma, Hiroyuki; Hyogotani, Akira; Kawakami, Satoshi; Yoshizawa, Akihiko; Asaka, Shiho; Ito, Ken-Ichi

2017-09-01

This study was performed to clarify whether preoperative serum albumin level is related to the prognosis of non-small cell lung cancer patients undergoing surgical resection, and the relationships between serum albumin level and clinicopathological characteristics of lung cancer patients with emphysema or pulmonary fibrosis. We retrospectively evaluated 556 patients that underwent surgical resection for non-small cell lung cancer. The correlation between preoperative serum albumin level and survival was evaluated. Patients were divided into three groups according to the findings on chest high-resolution computed tomography (normal lung, emphysema, and pulmonary fibrosis), and the relationships between serum albumin level and clinicopathological characteristics, including prognosis, were evaluated. The cut-off value of serum albumin level was set at 4.2g/dL. Patients with low albumin levels (albumin <4.2) had significantly poorer prognosis than those with high albumin levels (albumin ≥4.2) with regard to both overall survival and recurrence-free survival. Serum albumin levels in the emphysema group (n=48) and pulmonary fibrosis group (n=45) were significantly lower than that in the normal lung group (n=463) (p=0.009 and <0.001, respectively). Low serum albumin level was a risk factor in normal lung and pulmonary fibrosis groups, but not in the emphysema group. Preoperative serum albumin level was an important prognostic factor for overall survival and recurrence-free survival in patients with resected non-small cell lung cancer. Divided into normal lung, emphysema, and pulmonary fibrosis groups, serum albumin level showed no influence only in patients in the emphysema group. Copyright © 2017 Elsevier B.V. All rights reserved.

Recurrent amplification of RTEL1 and ABCA13 and its synergistic effect associated with clinicopathological data of gastric adenocarcinoma.

PubMed

Araújo, T M; Seabra, A D; Lima, E M; Assumpção, P P; Montenegro, R C; Demachki, S; Burbano, R M; Khayat, A S

2016-01-01

Despite progression in treatment of gastric cancer, prognosis of patients remains poor, in part due to the low rate of diagnosis during its early stages. This paradigm implies the necessity to identify molecular biomarkers for early gastric cancer diagnosis, as well as for disease monitoring, thus contributing to the development of new therapeutic approaches. In a previous study, performed by array-Comparative Genomic Hybridization, we described for the first time in literature recurrent amplification of RTEL1 and ABCA13 genes in gastric cancer. Thus, the aim of the present study was to validate recurrent amplification of RTEL1 and ABCA13 genes and associate CNV status with clinicopathological data. Results showed RTEL1 and ABCA13 amplification in 38 % of samples. Statistical analysis demonstrated that RTEL amplification is more common in older patients and more associated with intestinal type and ABCA13 amplification increases the risk of lymph node metastasis and is more common in men. Co-amplification of these genes showed a significant association with advanced staging. aCGH is a very useful tool for investigating novel genes associated with carcinogenesis and RTEL1 amplification may be important for the development of gastric cancer in older patients, besides being a probable event contributing for chromosomal instability in intestinal gastric carcinogenesis. ABCA13 amplification may have age-specific function and could be considered a useful marker for predicting lymph node metastasis in resected gastric cancer patients in early stage. Lastly, RTEL1 and ABCA13 synergistic effect may be considered as a putative marker for advanced staging in gastric cancer patients.

Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia.

PubMed

Matsuo, Koji; Ramzan, Amin A; Gualtieri, Marc R; Mhawech-Fauceglia, Paulette; Machida, Hiroko; Moeini, Aida; Dancz, Christina E; Ueda, Yutaka; Roman, Lynda D

2015-11-01

Although a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. A case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. The most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors. Older age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinicopathology Figures and Long-term Effects of Tamoxifen Plus Radiation on Survival of Women with Invasive Ductal Carcinoma and Triple Negative Breast Cancer.

PubMed

Payandeh, Mehrdad; Sadeghi, Masoud; Sadeghi, Edris; Aeinfar, Mehrnoush

2015-01-01

Triple negative breast cancer (TNBC), characterized as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 Her2 negative and accounting for 10-17% of all breast carcinomas, is only partially responsive to chemotherapy and suffers from a lack of clinically established targeted therapies. The aim of the current study was to evaluate the patterns of treatment and clinicopathology figures in Kurdish patients with triple-negative breast cancer, and to compare these to other reports. Between 2001 and 2014, 950 breast cancer patients were referred to our clinic. There were 74 female patients with TNBC, including 70 patients was invasive ductal carcinoma entered into our study. ER and PR positivity was defined as positive immunohistochemical staining in more than 10% of tumor cells. Immunohistochemistry assay with anti-HER2 antibodies was used to identify HER negative (0 and 1+) or positive (2+ and 3+). HER2 gene amplification was determined by fluorescent in situ hybridization (FISH). Overall survival (OS) was plotted with GraphPad Prism 5 Software using Kaplan-Meier and log-rank tests for comparison of results. The mean age in the first diagnosis for 70 patients with triple TNBC and invasive ductal carcinoma was 49.6 years that range of age was 27-82 years. All of the patients were female. Of 70 patients, 23 patients had metastasis. Thirty-two patients (45.7%) were treated with tamoxifen and 39 (55.7%) with radiotherapy. Three-year, 5-year and 10-year OS rates for all patients were 82%, 72% and 64%, respectively. The OS in our West Iran TNBC patients is less than reported elsewhere. However, treatment with combination of tamoxifen plus radiation increases the OS and reduces the mortality rate.

Safety of latex urinary catheters for the short time drainage

PubMed Central

Hosseinpour, Mehrdad; Noori, Saeed; Amir-Beigi, Mahdieh; Pourfakharan, Mohammad Hassan; Ehteram, Hassan; Hamsayeh, Mohadese

2014-01-01

Background: In this study, we attempt to identify the most appropriate catheter (silicone vs. latex) for short-term urinary catheterization. We compared the post-operative clinico-pathological complications between latex and silicone for short term catheterization in rabbits with hypospadias. Materials and Methods: Forty rabbits were used in our study to compare complications of catheterization. They were divided in two groups. Hypospadias like defect was created by a 1 cm long excision of the ventral urethra. For urethroplasty, we used tubularized incised plate technique. Latex and silicon catheters were used in groups 1 and 2, respectively. Post-operatively, routine laboratory urine test and complications (allergy, infection, bleeding) were compared in groups. Results: A total of 40 rabbits underwent hypospadias repair. Findings showed that there were no significant differences between groups based on urine test indices (P = NS). Urinary tract infection rate was 10% (2 rabbits) in latex and 0% in silicone groups (P = NS). There were no significant differences between groups regarding of cystitis grades between study groups (P = NS). Conclusion: It seems that urinary tract catheterization with latex catheters is a safe, feasible, and in-expensive procedure for short-term post-operative course in hypospadias surgery in patients without latex hypersensitivity. PMID:25125890

[Relationship between SLP-2 expression and prognosis in laryngeal squamous cell carcinoma and mammary invasive carcinoma].

PubMed

Cao, Wen-feng; Zhang, Li-yong; Zhang, Bin; Liu, Ming-bo; Liu, Zhi-hua; Sun, Bao-cun

2010-05-01

To study the expression of stomatin like protein-2 (SLP-2) at mRNA and protein levels in two kinds of malignant epithelial tumors, including laryngeal squamous cell carcinoma (LSCC) and invasive breast cancer, and to study the relations of SLP-2 expression and clinicopathologic parameters with the prognosis. RT-PCR and Western blot were used to detect the expression of SLP-2 mRNA and protein in LSCC and their normal counterparts (46 and 10 pair, respectively). Immunohistochemistry was carried on tissue array constructed from LSCC (104 cases) and breast cancer (263 cases), respectively. The association between SLP-2 expression and clinicopathologic parameters was analyzed. LSCC showed a higher expression of SLP-2 than that of their normal counterparts (negative expression) at mRNA (83%, 38/46) and protein (7/10) level. Immunohistochemical analysis of LSCC showed that compared with negative expression in normal laryngeal epithelium (0/20), a higher SLP-2 expression was detected in LSCC (36/104, P=0.000) and associated with the advanced clinical stage (P<0.01) and lymph node metastasis (P=0.003). Immunohistochemical study of invasive breast cancer demonstrated that compared with negative expression in normal breast tissue (0/10), more than one half of the cases showed a high SLP-2 expression (52.5%, 138/263, P=0.000) in breast cancer, which correlated with the tumor size (P=0.020), lymph node metastasis (P<0.01), advanced clinical stage (P<0.01), distant metastasis (P=0.002) and HER2/neu protein expression (P=0.037). Survival analysis showed a shorter overall survival probability in patients with a high SLP-2 expression. It was considered that lymph node metastasis, positive HER2/neu expression, and high-level SLP-2 expression may act as the independent prognostic factors for those tumors. A high expression level of SLP-2 may be associating with the development of invasion and metastasis in LSCC and breast cancer, and SLP-2 is also considered working as an independent factor indicating a poor prognosis clinically in breast cancer.

Expression and significance of Tie-1 and Tie-2 receptors, and angiopoietins-1, 2 and 4 in colorectal adenocarcinoma: Immunohistochemical analysis and correlation with clinicopathological factors

PubMed Central

Nakayama, Toshiyuki; Hatachi, Go; Wen, Chun-Yang; Yoshizaki, Ayumi; Yamazumi, Kazuyuki; Niino, Daisuke; Sekine, Ichiro

2005-01-01

AIM: There is strong evidence that tyrosine kinases are involved in the regulation of tumor progression, cellular growth and differentiation. Recently, many kinds of tyrosine kinase receptors have been reported, among them Tie-1 and Tie-2 receptors constitute a major class. Angiopoietin (Ang)-1 is known as a ligand of Tie-2 tyrosine kinase receptor. The objective of this study was to establish a comprehensive Tie-1 and Tie-2 and Ang-1, 2 and 4 expression profile in human colorectal adenocarcinomas. METHODS: We examined 96 cases of surgically resected human colorectal adenocarcinoma by immunohistochemistry and investigated the statistical correlation between the expressions of Ties and Angs and clinicopathological factors. RESULTS: Among the 96 cases of adenocarcinoma, 87 (90.6%), 92 (95.8%), 83 (86.5%), 89 (92.7%), and 76 cases (79.2%) showed positive staining in the cytoplasm of carcinoma cells for the Tie-1 and Tie-2 and Ang-1, 2 and 4 proteins, respectively. Histologically, the expressions of Ties and Angs were variable. The expressions of Ties and Angs were correlated with several clinicopathological factors, but did not correlate with the presence of lymph node metastasis. Ties and Angs were highly expressed in human colorectal adenocarcinoma cells. CONCLUSION: These findings suggest that the Tie-Ang receptor-ligand complex is one of the factors involved in the cellular differentiation and progression of human colorectal adenocarcinoma. PMID:15742397

Phosphorylated Protein Kinase C (Zeta/Lambda) Expression in Colorectal Adenocarcinoma and Its Correlation with Clinicopathologic Characteristics and Prognosis.

PubMed

Yeo, Min-Kyung; Kim, Ji Yeon; Seong, In-Ock; Kim, Jin-Man; Kim, Kyung-Hee

2017-01-01

Background: Protein kinase C zeta/lambda (PKCζ/λ) is a family of protein kinase enzymes that contributes to cell proliferation and regulation, which are important for cancer development. PKCζ/λ has been shown to be an important regulator of tumorigenesis in intestinal cancer. The phosphorylated form of PKCζ/λ, p-PKCζ/λ, is suggested as an active form of PKCζ/λ. However, p-PKCζ/λ expression and its clinicopathologic implication in colorectal adenocarcinoma (CRAC) are unclear. Methods: Seven whole-tissue sections of malignant polyps containing both non-neoplastic and neoplastic mucosa, 11 adenomas with low-grade dysplasia, and 173 CRACs were examined by immunohistochemistry and western blot assay for p-PKCζ/λ protein expression. The association of p-PKCζ/λ expression with clinicopathologic factors including patient survival was studied. Results: In non-neoplastic epithelia, p-PKCζ/λ showed a weak cytoplasmic immunostaining. Adenomas and CRACs demonstrated up-regulated p-PKCζ/λ detection. Cytoplasmic p-PKCζ/λ expression was higher in CRAC than in adenoma. In CRACs, p-PKCζ/λ expression was inversely correlated with pathologic TNM stage (I-II versus III-IV) and poor differentiation. Statistical correlations between low expression of p-PKCζ/λ with shortened overall survival and disease-free survival were seen (p=0.004 and p=0.034, respectively). Conclusions: P-PKCζ/λ overexpression is implicated in tumorigenesis but down-regulation was a poor prognostic factor in CRAC.

KRAS mutations and CDKN2A promoter methylation show an interactive adverse effect on survival and predict recurrence of rectal cancer.

PubMed

Kohonen-Corish, Maija R J; Tseung, Jason; Chan, Charles; Currey, Nicola; Dent, Owen F; Clarke, Stephen; Bokey, Les; Chapuis, Pierre H

2014-06-15

Colonic and rectal cancers differ in their clinicopathologic features and treatment strategies. Molecular markers such as gene methylation, microsatellite instability and KRAS mutations, are becoming increasingly important in guiding treatment decisions in colorectal cancer. However, their association with clinicopathologic variables and utility in the management of rectal cancer is still poorly understood. We analyzed CDKN2A gene methylation, CpG island methylator phenotype (CIMP), microsatellite instability and KRAS/BRAF mutations in a cohort of 381 rectal cancers with extensive clinical follow-up data. BRAF mutations (2%), CIMP-high (4%) and microsatellite instability-high (2%) were rare, whereas KRAS mutations (39%), CDKN2A methylation (20%) and CIMP-low (25%) were more common. Only CDKN2A methylation and KRAS mutations showed an association with poor overall survival but these did not remain significant when analyzed with other clinicopathologic factors. In contrast, this prognostic effect was strengthened by the joint presence of CDKN2A methylation and KRAS mutations, which independently predicted recurrence of cancer and was associated with poor overall and cancer-specific survival. This study has identified a subgroup of more aggressive rectal cancers that may arise through the KRAS-p16 pathway. It has been previously shown that an interaction of p16 deficiency and oncogenic KRAS promotes carcinogenesis in the mouse and is characterized by loss of oncogene-induced senescence. These findings may provide avenues for the discovery of new treatments in rectal cancer. © 2013 UICC.

Atypical teratoid/rhabdoid tumours: clinicopathological characteristics, prognostic factors and outcomes of 22 children from 2010 to 2015 in China.

PubMed

Wang, Rui-Fen; Guan, Wen-Bin; Yan, Yu; Jiang, Bo; Ma, Jie; Jiang, Ma-Wei; Wang, Li-Feng

2016-10-01

Atypical teratoid/rhabdoid tumours (AT/RTs) are rare, highly malignant tumours of the central nervous system (CNS) with poor prognosis that usually affect young children. The aim of this study was to assess the clinicopathological features and prognostic factors of AT/RTs. Here, we describe the clinicopathological and immunohistochemical characteristics, along with the treatments and outcomes, of 22 patients with AT/RTs treated in our hospital from 2010 to 2015. Morphologically, cytoplasmic vacuoles, the most common characteristic in our cases, were observed in 68% of the cases. Similarly, vesicular nuclei were detected in 68% of the cases. However, rhabdoid cells were found in only 59.1% of the cases and were not observed in 40.9% of the cases. Immunohistochemical analysis revealed loss of nuclear INI1 expression in all 22 cases. Age, surgical resection and adjuvant therapy, but not tumour location, were associated with AT/RTs patient prognosis. Our results showed that cells with cytoplasmic vacuoles or with vesicular nuclei are more common than rhabdoid cells in patients with AT/RTs and that a lack of INI1 protein expression is the most useful marker for the differential diagnosis of AT/RTs. Young age is a negative prognostic factor, whereas gross total surgical resection and adjuvant therapy are positive prognostic factors for AT/RT patients. Copyright © 2016 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

[Clinicopathological characterization of true hermaphroditism complicated with seminoma and review of the literature].

PubMed

Hua, Xing; Liu, Shao-Jie; Lu, Lin; Li, Chao-Xia; Yu, Li-Na

2012-08-01

To study the clinicopathological characteristics and diagnosis of true hermaphroditism complicated with seminoma. We retrospectively analyzed the clinicopathological data of a case of true hermaphroditism complicated with seminoma and reviewed the related literature. The patient was a 42-year-old male, admitted for bilateral lower back pain and discomfort. CT showed a huge mass in the lower middle abdomen. Gross pathological examination revealed a mass of uterine tissue, 7 cm x 2 cm x 6 cm in size, with bilateral oviducts and ovarian tissue. There was a cryptorchidism (4.0 cm x 2.5 cm x 1.5 cm) on the left and a huge tumor (22 cm x9 cm x6 cm) on the right of the uterine tissue. The tumor was completely encapsulated, with some testicular tissue. Microscopically, the tumor tissue was arranged in nests or sheets divided and surrounded by fibrous tissue. The tumor cells were large, with abundant and transparent cytoplasm, deeply stained nuclei, coarse granular chromatins, visible mitosis, and infiltration of a small number of lymphocytes in the stroma. The karyotype was 46, XX. Immunohistochemistry showed that PLAP and CD117 were positive, while the AFP, Vimentin, EMA, S100, CK-LMW, Desmin, CD34 and CD30 were negative, and Ki-67 was 20% positive. A small amount of residual normal testicular tissue was seen in the tumor tissue. True hermaphroditism complicated with seminoma is rare. Histopathological analysis combined with immunohistochemical detection is of great value for its diagnosis and differential diagnosis.

CD147 as a Novel Prognostic Biomarker for Hepatocellular Carcinoma: A Meta-Analysis.

PubMed

Peng, Fei; Li, Hui; You, Qian; Li, Hongru; Wu, Dongwen; Jiang, Chunxiang; Deng, Guangtong; Li, Yan; Li, Yuyan; Wu, Yi

2017-01-01

We conducted a meta-analysis to investigate the controversial association of CD147 expression with HCC prognosis and clinicopathological characteristics. Eight studies from PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wanfang databases (1988-2016) were considered. The associations between CD147 expression and clinicopathological parameters and overall survival (OS) or DFS/RFS were reassessed using the meta-analysis for odds ratio (OR) or hazard ratio (HR) and 95% confidence interval (CI). CD147 expression was associated with DFS/RFS (HR = 3.26; 95% CI: 1.82-5.83; P < 0.0001) but not with OS (HR = 1.35; 95% CI: 0.56-3.29; P = 0.51). We also delved deeper into the association between median survival time and CD147 expression owing to significant heterogeneity and found significant differences between high and low CD147 expression groups with respect to median survival time. CD147 expression was closely associated with the TNM stage (OR = 0.18; 95% CI: 0.04-0.85; P = 0.03) and venous invasion (OR = 6.29; 95% CI: 1.70-23.20; P = 0.006). In contrast, there was no association between CD147 expression and tumor stage, cirrhosis, differentiation, lymph node metastasis, HBsAg, and serum AFP levels. Thus, CD147 expression is potentially closely related to HCC survival and associated clinicopathological parameters, paving the way for further research.

Clinicopathological characteristics and prognostic factors of primary gastrointestinal lymphoma: a 22-year experience from South China.

PubMed

Li, Minrui; Zhang, Shenghong; Gu, Fang; Xiao, Weiwei; Yao, Jiayan; Chao, Kang; Chen, Minhu; Li, Juan; Zhong, Bihui

2014-01-01

Primary gastrointestinal lymphoma (PGIL) is a kind of relatively rare cancer and easily misdiagnosed due to its unspecific signs in digestive tract. Data including 216 patients histologically diagnosed as PGIL between January 1991 and October 2012 from The First Affiliated Hospital of Sun Yat-sen University were reviewed. This study was to investigate the clinicopathological features and prognosis, and make the comparison between the different sites of PGIL. Abdominal pain (75.9%) was the most frequent symptom and intermediate-grade lymphoma (53.7%) presented as the most common histological type. Intestine (55.1%) was the most common site involved, followed by stomach (38.5%), both intestine and stomach (6.4%). PGIL of different original site showed distinguished clinicopathological characteristics that patients in Stomach and GI group were older than Intestine group (Mean age: 54 and 53 vs. 43 years, p<0.001); diarrhea, B symptom, abdominal mass and complication occurred more in intestine group. Histologically, high-grade lymphoma (especially T-cell type) almost located in Intestine group (82.5%). Five-year overall survival (OS) and event-free survival (EFS) for all PGIL patients were 56.4% and 49.3%, respectively. Stomach group had better OS (72.3%) and EFS (48.4%) than Intestine group (43.1% and 23.6% respectively), but it lost the significance in the multivariate analysis. Univariate and multivariate analysis revealed that performance status, lactate dehydrogenase (LDH) level and histological type were independent prognostic factors for PGIL.

The Implications of Endoscopic Ulcer in Early Gastric Cancer: Can We Predict Clinical Behaviors from Endoscopy?

PubMed

Lee, Yoo Jin; Kim, Jie-Hyun; Park, Jae Jun; Youn, Young Hoon; Park, Hyojin; Kim, Jong Won; Choi, Seung Ho; Noh, Sung Hoon

2016-01-01

The presence of ulcer in early gastric cancer (EGC) is important for the feasibility of endoscopic resection, only a few studies have examined the clinicopathological implications of endoscopic ulcer in EGC. To determine the role of endoscopic ulcer as a predictor of clinical behaviors in EGC. Data of 3,270 patients with EGC who underwent surgery between January 2005 and December 2012 were reviewed. Clinicopathological characteristics were analyzed in relation to the presence and stage of ulcer in EGC. Based on endoscopic findings, the stage of ulcer was categorized as active, healing, or scar. Logistic regression analysis was performed to analyze factors associated with lymph node metastasis (LNM). 2,343 (71.7%) patients had endoscopic findings of ulceration in EGC. Submucosal (SM) invasion, LNM, lymphovascular invasion (LVI), perineural invasion, and undifferentiated-type histology were significantly higher in ulcerative than non-ulcerative EGC. Comparison across different stages of ulcer revealed that SM invasion, LNM, and LVI were significantly associated with the active stage, and that these features exhibited significant stage-based differences, being most common at the active stage, and least common at the scar stage. The presence of endoscopic ulcer and active status of the ulcer were identified as independent risk factors for LNM. Ulcerative EGC detected by endoscopy exhibited more aggressive behaviors than non-ulcerative EGC. Additionally, the endoscopic stage of ulcer may predict the clinicopathological behaviors of EGC. Therefore, the appearance of ulcers should be carefully evaluated to determine an adequate treatment strategy for EGC.

Macrocystic ductal adenocarcinoma of prostate: A rare gross appearance of prostate cancer.

PubMed

Kojima, Fumiyoshi; Koike, Hiroyuki; Matsuzaki, Ibu; Iwahashi, Yoshifumi; Warigaya, Kenji; Fujimoto, Masakazu; Ono, Kazuo; Urata, Youji; Kohjimoto, Yasuo; Hara, Isao; Murata, Shin-Ichi

2017-04-01

Macroscopic cyst-formation by prostatic adenocarcinoma, herein referred to as macrocystic prostatic adenocarcinoma (MPA), is extremely rare. To date, no studies of prostate cancer performed based on gross cystic appearance have been reported. MPA can include various diseases, one of which is cystadenocarcinoma. Several cases of ductal adenocarcinoma exhibiting a macrocystic appearance have recently been reported; however, the histological and clinicopathological characteristics of MPAs have yet to be characterized and established. Therefore, we aimed to determine the histological and clinicopathological characteristics of MPA, via a multi-institutional investigation. We discovered five patients with MPA out of 1559 treated patients (0.32%); all cases were ductal adenocarcinomas. MPA was found to have three growth patterns: Two cases showed a prevalence of exuberant papillary proliferation with a fibrovascular core in the macroscopic multilocular cysts. Two others predominantly exhibited multilocular cysts lined by flat epithelium with foci of low papillae, and the fifth had a cystic lesion with intracancerous necrosis. Three of the cases showed extraprostatic invasion; however, none of the patients experienced recurrence during the follow-up period. Each predominant growth pattern tended to exhibit unique clinicopathological characteristics with respect to serum prostate specific antigen level and tumor size and location. In conclusion, we demonstrated that MPA is a ductal adenocarcinoma that is composed of intracystic exuberant papillary proliferation and flat proliferation with foci of low papillae, both of which might exhibit different clinicopathololgical appearances. Copyright © 2017 Elsevier Inc. All rights reserved.

A Clinico-Pathological and Immunoparasitological Study on Toxocariasis in Egypt.

DTIC Science & Technology

1978-05-31

Governorates. Similarly Toxocariasis in man at Dakahleya Governorate, Siwa Oasis, Qena and Asswan Governorates were done together with the determination of the...as being a cause of blindness in Egyptian children results interpreted on this light of the prevalence of infection in stray dogs and cats, the high

Clinicopathological significance of c-MYC in esophageal squamous cell carcinoma.

PubMed

Lian, Yu; Niu, Xiangdong; Cai, Hui; Yang, Xiaojun; Ma, Haizhong; Ma, Shixun; Zhang, Yupeng; Chen, Yifeng

2017-07-01

Esophageal squamous cell carcinoma is one of the most common malignant tumors. The oncogene c-MYC is thought to be important in the initiation, promotion, and therapy resistance of cancer. In this study, we aim to investigate the clinicopathologic roles of c-MYC in esophageal squamous cell carcinoma tissue. This study is aimed at discovering and analyzing c-MYC expression in a series of human esophageal tissues. A total of 95 esophageal squamous cell carcinoma samples were analyzed by the western blotting and immunohistochemistry techniques. Then, correlation of c-MYC expression with clinicopathological features of esophageal squamous cell carcinoma patients was statistically analyzed. In most esophageal squamous cell carcinoma cases, the c-MYC expression was positive in tumor tissues. The positive rate of c-MYC expression in tumor tissues was 61.05%, obviously higher than the adjacent normal tissues (8.42%, 8/92) and atypical hyperplasia tissues (19.75%, 16/95). There was a statistical difference among adjacent normal tissues, atypical hyperplasia tissues, and tumor tissues. Overexpression of the c-MYC was detected in 61.05% (58/95) esophageal squamous cell carcinomas, which was significantly correlated with the degree of differentiation (p = 0.004). The positive rate of c-MYC expression was 40.0% in well-differentiated esophageal tissues, with a significantly statistical difference (p = 0.004). The positive rate of c-MYC was 41.5% in T1 + T2 esophageal tissues and 74.1% in T3 + T4 esophageal tissues, with a significantly statistical difference (p = 0.001). The positive rate of c-MYC was 45.0% in I + II esophageal tissues and 72.2% in III + IV esophageal tissues, with a significantly statistical difference (p = 0.011). The c-MYC expression strongly correlated with clinical staging (p = 0.011), differentiation degree (p = 0.004), lymph node metastasis (p = 0.003), and invasion depth (p = 0.001) of patients with esophageal squamous cell carcinoma. The c-MYC was differentially expressed in a series of human esophageal tissues, and the aberrant c-MYC expression could be a potential factor in carcinogenesis and progression of esophageal squamous cell carcinoma. There was a statistical signification for c-MYC in esophageal squamous cell carcinoma patients to analyze clinicopathological features. It possibly becomes a new diagnostic indicator of esophageal squamous cell carcinoma.

Progranulin expression in breast cancer with different intrinsic subtypes.

PubMed

Li, Li Qin; Min, Li Shan; Jiang, Qun; Ping, Jin Liang; Li, Jing; Dai, Li Cheng

2012-04-15

Progranulin is a newly discovered 88-kDa glycoprotein originally purified from the highly tumorigenic mouse teratoma-derived cell line PC. We found that high progranulin expression was associated with higher breast carcinoma angiogenesis, reflected by increased vascular endothelial growth factor expression and higher microvessel density. However, no immunohistochemical evidence currently exists to correlate progranulin expression with clinicopathological features in different intrinsic subtypes of breast carcinoma biopsies. The aim of this study was to investigate the progranulin expression profiles in the intrinsic subtypes of breast carcinomas and their relevance to histopathological and clinicopathological features. Tissue blocks containing 264 cases of breast carcinomas from 2006 to 2009 were classified as different intrinsic subtypes. Tissues of four intrinsic subtypes were immunostained for progranulin, vascular endothelial growth factor and CD105. Their relevance to histopathological and clinicopathological features was also analyzed. Twenty tissue samples from breast fibroadenomas were included in this study. Progranulin expression showed no significant differences in different intrinsic subtypes, although an increasing tendency could be found in the triple-negative breast cancer (TNBC) subgroup (χ(2)=5.00, df=3, p=0.17). However, differences were significant when pathologically node metastasis-positive (pN(+)) TNBC were excluded (χ(2)=17.84, df=3, p<0.01). Some clinicopathological parameters, including CK5/6 (χ(2)=0.08, df=3, p=0.78), E-cadherin (χ(2)=0.71, df=3, p=0.40) and P53 (χ(2)=0.05, df=3, p=0.83), displayed no correlation with activity of progranulin in pathologically node metastasis-negative (pN(-)) TNBC. It was noted that the EGFR expression level of the pN(-) TNBC subtype was significantly higher in cases with strong progranulin expression than in cases with weak progranulin expression (χ(2)=11.26, df=1, p<0.01). A significantly higher expression level of progranulin in pN(-) TNBC suggests that progranulin is a promising new target for pN(-) TNBC treatment. Strong expression of progranulin correlates with positive EGFR expression in the pN(-) TNBC subtype. The close relationship between EGFR and progranulin/VEGF/CD105 expression may partly play a role in high angiogenesis levels in the pN(-) TNBC subtype. Copyright © 2012 Elsevier GmbH. All rights reserved.

Serum soluble E-cadherin is a potential prognostic marker in esophageal squamous cell carcinoma.

PubMed

Chung, Y; Law, S; Kwong, D L W; Luk, J M

2011-01-01

E-cadherin is a well-documented tumor suppressor with downregulated expression in many cancer types. Upon proteolytic cleavage, a soluble form of 80-kDa degradation fragment, known as soluble E-cadherin (s-Ecad), is present in circulation; its level in sera of cancer patients is significantly associated with metastasis, recurrence, and prognosis in some malignancies. The present study investigated the association of s-Ecad with clinicopathological characteristics of patients with esophageal squamous cell carcinoma (ESCC) and its prognostic significance. A cohort of 97 patients who underwent surgery alone (n= 56) or neoadjuvant chemoradiation therapy and surgery (CRT) (n= 41) was recruited for this study. Serum samples were collected at operation (surgery group) and pre- and post-CRT treatment (CRT group) for measurement of s-Ecad protein by enzyme linked immunosorbent assay. Serum s-Ecad levels were correlated with clinicopathological parameters as well as survival. Univariate analysis showed no significant relationship between serum s-Ecad level and clinicopathological parameters for all sets of samples. Survival analysis showed that in patients who had surgical resection only, those with s-Ecad levels equal to or below the median value survived significantly longer than those with levels above the median (median survival 25.6 vs. 14.1 months, P= 0.012). Multivariate analysis showed that pathological N stage, M stage, R category, and serum s-Ecad level were significant independent prognostic factors for ESCC patients who underwent surgery only. The hazard ratio for s-Ecad was 1.104 (95% CI: 1.026-1.187) and P= 0.008. Serum s-Ecad was detected in ESCC patients and its potential as an independent prognostic marker requires further investigation. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Prognostic and predictive values of oncogenic BRAF, NRAS, c-KIT and MITF in cutaneous and mucous melanoma.

PubMed

Pracht, M; Mogha, A; Lespagnol, A; Fautrel, A; Mouchet, N; Le Gall, F; Paumier, V; Lefeuvre-Plesse, C; Rioux-Leclerc, N; Mosser, J; Oger, E; Adamski, H; Galibert, M-D; Lesimple, T

2015-08-01

Mutations of BRAF, NRAS and c-KIT oncogenes are preferentially described in certain histological subtypes of melanoma and linked to specific histopathological features. BRAF-, MEK- and KIT-inhibitors led to improvement in overall survival of patients harbouring mutated metastatic melanoma. To assess the prevalence and types of BRAF, NRAS, c-KIT and MITF mutations in cutaneous and mucous melanoma and to correlate mutation status with clinicopathological features and outcome. Clinicopathological features and mutation status of 108 samples and of 98 consecutive patients were, respectively, assessed in one retrospective and one prospective study. Clinicopathological features were correlated with mutation status and the predictive value of these mutations was studied. This work identified significant correlations between BRAF mutations and melanoma occurring on non-chronic sun-damaged skin and superficial spreading melanoma (P < 0.05) on one hand, and between NRAS mutations and nodular melanoma (P < 0.05) on the other hand. Younger age (P < 0.05), microscopic (P < 0.05) and macroscopic (P < 0.05) lymphatic involvement at diagnosis of primary melanoma were significantly linked to BRAF mutations. A mutated status was a positive predictive factor of a response to BRAF inhibitors (OR = 3.44). Mutated melanoma showed a significantly (P = 0.038) higher objective response rate to cytotoxic chemotherapy (26.3%) than wild-type tumours (6.7%). Clinical and pathological characteristics of the primary melanoma differed between wild-type and BRAF- or NRAS-mutated tumours. Patients with BRAF-mutated tumours were younger at diagnosis of primary melanoma. Patients carrying mutations showed better responses better to specific kinase inhibitors and interestingly also to systemic cytotoxic chemotherapy. © 2015 European Academy of Dermatology and Venereology.

[Prognostic differences of phenotypes in pT1-2N0 invasive breast cancer: a large cohort study with cluster analysis].

PubMed

Wang, Z; Wang, W H; Wang, S L; Jin, J; Song, Y W; Liu, Y P; Ren, H; Fang, H; Tang, Y; Chen, B; Qi, S N; Lu, N N; Li, N; Tang, Y; Liu, X F; Yu, Z H; Li, Y X

2016-06-23

To find phenotypic subgroups of patients with pT1-2N0 invasive breast cancer by means of cluster analysis and estimate the prognosis and clinicopathological features of these subgroups. From 1999 to 2013, 4979 patients with pT1-2N0 invasive breast cancer were recruited for hierarchical clustering analysis. Age (≤40, 41-70, 70+ years), size of primary tumor, pathological type, grade of differentiation, microvascular invasion, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were chosen as distance metric between patients. Hierarchical cluster analysis was performed using Ward's method. Cophenetic correlation coefficient (CPCC) and Spearman correlation coefficient were used to validate clustering structures. The CPCC was 0.603. The Spearman correlation coefficient was 0.617 (P<0.001), which indicated a good fit of hierarchy to the data. A twelve-cluster model seemed to best illustrate our patient cohort. Patients in cluster 5, 9 and 12 had best prognosis and were characterized by age >40 years, smaller primary tumor, lower histologic grade, positive ER and PR status, and mainly negative HER-2. Patients in the cluster 1 and 11 had the worst prognosis, The cluster 1 was characterized by a larger tumor, higher grade and negative ER and PR status, while the cluster 11 was characterized by positive microvascular invasion. Patients in other 7 clusters had a moderate prognosis, and patients in each cluster had distinctive clinicopathological features and recurrent patterns. This study identified distinctive clinicopathologic phenotypes in a large cohort of patients with pT1-2N0 breast cancer through hierarchical clustering and revealed different prognosis. This integrative model may help physicians to make more personalized decisions regarding adjuvant therapy.

Expression of chemokine receptor CCR7 is a negative prognostic factor for patients with gastric cancer: a meta-analysis.

PubMed

Du, Peizhun; Liu, Yongchao; Ren, Hong; Zhao, Jing; Zhang, Xiaodan; Patel, Rajan; Hu, Chenen; Gan, Jun; Huang, Guangjian

2017-03-01

The prognostic significance of CC chemokine receptor type 7 (CCR7) for survival of patients with gastric cancer remains controversial. To investigate the impacts of CCR7 on clinicopathological findings and survival outcome in gastric cancer, we performed a meta-analysis. A comprehensive search in PubMed, Embase, the Cochrane Library, and the CNKI database (1966 to November 2015) was undertaken for relevant studies. The relative risk and hazard ratios with their 95 % confidence intervals were used as measures to investigate the correlation between CCR7 expression and clinicopathological findings and overall survival rate. Sensitivity analysis was conducted to assess the stability of outcomes. Fifteen eligible studies comprising 1697 participants were included in our analysis. The pooled relative risks indicated CCR7 expression was significantly associated with deeper tumor invasion [0.61, 95 % confidence interval (CI) 0.45-0.84, p = 0.003], advanced stage (0.47, 95 % CI 0.32-0.69, p < 0.001), vascular invasion (2.12, 95 % CI 1.20-3.73, p = 0.009), lymph node metastasis (2.00, 95 % CI 1.48-2.70, p < 0.001), and lymphatic invasion (1.98, 95 % CI 1.43-2.72, p < 0.001) but not with age, tumor size, and histological type. The pooling of hazard ratios showed a significant relationship between positive CCR7 expression and worse 5-year overall survival rate (0.46, 95 % CI 0.31-0.70, p < 0.001). Our meta-analysis indicated high CCR7 expression is likely to be a negative clinicopathological prognostic factor for patients with gastric cancer and to predict a worse long-term survival outcome.

Coexistence of gastrointestinal stromal tumors and gastric adenocarcinomas.

PubMed

Yan, Yan; Li, Ziyu; Liu, Yiqiang; Zhang, Lianhai; Li, Jiyou; Ji, Jiafu

2013-04-01

The purpose of this study is to detect the clinicopathology of gastrointestinal stromal tumors (GISTs) occurring synchronously with gastric adenocarcinomas and to unveil the potential underlying relationship between the synchronous GIST and gastric adenocarcinoma. This study included 15 patients with incidental GISTs found during operations for gastric adenocarcinoma and 30 patients who underwent gastrectomy for gastric cancer without discovering GIST between January 2005 and December 2010 at the Beijing Cancer Institute. We collected the clinicopathological data and analyzed the KIT/PDGFRA mutational status of GISTs, corresponding gastric adenocarcinoma specimens, and the normal tissue around the cancer lesions. Additionally, as a control group, the mutational status of the patients with gastric adenocarcinoma and no other tumors was assayed. Overall, 18 GISTs were found in 15 gastric adenocarcinoma patients. Multiple GIST lesions were found in three cases (20 %). The patients' age ranged from 46 to 85 years, with an average of 67.6 years. The average size of the GISTs was 0.85 cm. All mesenchymal lesions showed low proliferative activity, were of low or very low risk, and were identified as CD117-positive by immunostaining. In GIST lesions, mutations in KIT were detected in 7 out of 13 cases, and of these mutations, 6 were found in exon 11 (46.2 %), and 1 was found in exon 9 (7.7 %). A total of five deletions and one point mutation were in exon 11, and one insertion was in exon 9. Mutations were not detected in exon 17 or 13 of KIT. There was no remarkable mutation analyzed in the gastric adenocarcinoma lesions or normal tissues from either the test or control groups. Clinicopathological profiles and molecular analysis of KIT/PDGFRA showed no obvious relationship between gastric cancer and GISTs in tumor genesis, such as similar oncogene mutations.

Chronic atelectasis of the left lower lobe: a clinicopathological condition equivalent to middle lobe syndrome

PubMed Central

Hamad, Abdel-Mohsen; Elmistekawy, Elsayed; Elatafy, Elatafy

2012-01-01

OBJECTIVES Middle lobe syndrome is a well-known clinical condition. In this retrospective study, we report our experience with a similar clinicopathological condition affecting the left lower lobe. METHODS The data of 17 patients with atelectasis or bronchiectasis of the left lower lobe who underwent lobectomy during the period from January 2000 to December 2011 were reviewed. Demographic, clinical, radiological and surgical data were collected. RESULTS Seventeen patients were included in this study, only one adult male patient of 52 years and 16 children. The paediatric patients were 10 boys and 6 girls, their age ranged from 2 to 11 years, mean 6.19 ± 2.6 years. Most patients presented with recurrent respiratory infection 15/17 (88.2%). The lag time before referral to surgery ranged from 3 to 48 months, mean 17.59 ± 13.1 months. Radiological signs of bronchiectasis were found in 11 (64.7%) patients. Bronchoscopy showed patent lower lobe bronchus in all patients. The criteria for lobectomy were evidence of bronchiectasis [11 (64.71%) patients], persistent atelectasis of the lobe after bronchoscopy and intensive medical therapy for a maximum of 2 months [6 (35.29%) patients]. Histopathological examination showed bronchiectasis in 11 (64.71%) patients, fibrosing pneumonitis in 4 (23.53%) patients and peribronchial inflammation in 2 (11.76%) patients. Most patients were doing well 1 year after surgery. CONCLUSIONS Chronic atelectasis of the left lower lobe is a clinicopathological condition equivalent to middle lobe syndrome. Impaired collateral ventilation together with airway plugging with secretion is an accepted explanation. Surgical resection is indicated for bronchiectatic lobe or failure of 2-month intensive medical therapy to resolve lobar atelectasis. PMID:22761114

Chronic atelectasis of the left lower lobe: a clinicopathological condition equivalent to middle lobe syndrome.

PubMed

Hamad, Abdel-Mohsen; Elmistekawy, Elsayed; Elatafy, Elatafy

2012-10-01

Middle lobe syndrome is a well-known clinical condition. In this retrospective study, we report our experience with a similar clinicopathological condition affecting the left lower lobe. The data of 17 patients with atelectasis or bronchiectasis of the left lower lobe who underwent lobectomy during the period from January 2000 to December 2011 were reviewed. Demographic, clinical, radiological and surgical data were collected. Seventeen patients were included in this study, only one adult male patient of 52 years and 16 children. The paediatric patients were 10 boys and 6 girls, their age ranged from 2 to 11 years, mean 6.19 ± 2.6 years. Most patients presented with recurrent respiratory infection 15/17 (88.2%). The lag time before referral to surgery ranged from 3 to 48 months, mean 17.59 ± 13.1 months. Radiological signs of bronchiectasis were found in 11 (64.7%) patients. Bronchoscopy showed patent lower lobe bronchus in all patients. The criteria for lobectomy were evidence of bronchiectasis [11 (64.71%) patients], persistent atelectasis of the lobe after bronchoscopy and intensive medical therapy for a maximum of 2 months [6 (35.29%) patients]. Histopathological examination showed bronchiectasis in 11 (64.71%) patients, fibrosing pneumonitis in 4 (23.53%) patients and peribronchial inflammation in 2 (11.76%) patients. Most patients were doing well 1 year after surgery. Chronic atelectasis of the left lower lobe is a clinicopathological condition equivalent to middle lobe syndrome. Impaired collateral ventilation together with airway plugging with secretion is an accepted explanation. Surgical resection is indicated for bronchiectatic lobe or failure of 2-month intensive medical therapy to resolve lobar atelectasis.

Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment.

PubMed

Hasumi, Katsuhiko; Sugiyama, Yuko; Sakamoto, Kimihiko; Akiyama, Futoshi

2013-12-01

Natural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial carcinomas arising from endometrial hyperplasia. Clinicopathologically 131 patients with endometrial carcinoma measuring ≤10 mm in diameter ("small endometrial carcinoma") were studied to get useful information for early diagnosis, treatment, and histogenesis. The entire endometrium of surgically removed uterus was step-cut and examined. The patients were, on average, 5 years younger than the controls whose carcinomas measure >10 mm (P < 0.0001). Of the 131 patients, 20% were asymptomatic although only 5% of the controls were asymptomatic (P < 0.0001). Seventy-six percent had the carcinomas located in the upper third section of the uterine corpus. Macroscopically 44% of the tumors were flat and 56% were elevated. Incidence of nodal and ovarian metastases were <1%. Forty percent of "small endometrial carcinomas" were associated with endometrial hyperplasia and 60% were not. It is logical to believe that there are two pathways of endometrial carcinogenesis: carcinomas occurring from hyperplasia (40%) and carcinomas occurring from normal endometrium (60%). As hyperplasia-carcinoma sequence is not a main route, we cannot probably prevent carcinomas only by treatment of hyperplasia. Effort must be focused on detecting early de novo carcinomas. As most "small endometrial carcinomas" arise in the upper third of the corpus, careful endometrial sampling there is important for early detection. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers.

PubMed

Kobayashi, Yusuke; Nakamura, Kanako; Nomura, Hiroyuki; Banno, Kouji; Irie, Haruko; Adachi, Masataka; Iida, Miho; Umene, Kiyoko; Nogami, Yuya; Masuda, Kenta; Kisu, Iori; Ueki, Arisa; Yamagami, Wataru; Kataoka, Fumio; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke

2015-03-01

Synchronous primary endometrial and ovarian cancers have been an important topic in clinical medicine because it is sometimes difficult to distinguish whether there are 2 primary tumors or a single primary tumor and an associated metastasis. In addition, although these tumors are recommended for either immunohistochemistry for DNA mismatch repair (MMR) proteins or a microsatellite instability test in the Bethesda guidelines as Lynch syndrome-associated cancers, few studies have completed these analyses. In this study, we characterized the clinicopathologic features and the expression pattern of MMR proteins in synchronous primary endometrial and ovarian cancers. Clinicopathologic features and the expression pattern of MMR proteins (MLH1, MSH2, and MSH6) were characterized and analyzed in 32 synchronous primary endometrial and ovarian cancers. Most synchronous cancers are endometrioid type (endometrioid/endometrioid) (n = 24, 75%), grade 1 (n = 19, 59.4%), and diagnosed as stage I (n = 15, 46.9%) in both endometrium and ovary. It is worth mentioning that 75% of the patients (n = 24) had endometriosis, which was more common (n = 21, 87.5%) in endometrioid/endometrioid cancers, whereas only 3 cases (37.5%) were of different histology (P = 0.018). Loss of expression of at least 1 MMR protein was observed in 17 (53.1%) of the endometrial tumors and in 10 (31.3%) of ovarian tumors. Only 4 cases (12.5%) that had specific MMR protein loss showed the same type of loss for both endometrial and ovarian tumors, in which 3 of the cases were losses in MLH1. One case showed concordant MSH6 protein loss, although the cases did not meet the Amsterdam criteria II. These results suggest that most synchronous primary endometrial ovarian cancers are not hereditary cancers caused by germ line mutations but rather sporadic cancers.

A prognostic classifier for patients with colorectal cancer liver metastasis, based on AURKA, PTGS2 and MMP9.

PubMed

Goos, Jeroen A C M; Coupé, Veerle M H; van de Wiel, Mark A; Diosdado, Begoña; Delis-Van Diemen, Pien M; Hiemstra, Annemieke C; de Cuba, Erienne M V; Beliën, Jeroen A M; Menke-van der Houven van Oordt, C Willemien; Geldof, Albert A; Meijer, Gerrit A; Hoekstra, Otto S; Fijneman, Remond J A

2016-01-12

Prognosis of patients with colorectal cancer liver metastasis (CRCLM) is estimated based on clinicopathological models. Stratifying patients based on tumor biology may have additional value. Tissue micro-arrays (TMAs), containing resected CRCLM and corresponding primary tumors from a multi-institutional cohort of 507 patients, were immunohistochemically stained for 18 candidate biomarkers. Cross-validated hazard rate ratios (HRRs) for overall survival (OS) and the proportion of HRRs with opposite effect (P(HRR < 1) or P(HRR > 1)) were calculated. A classifier was constructed by classification and regression tree (CART) analysis and its prognostic value determined by permutation analysis. Correlations between protein expression in primary tumor-CRCLM pairs were calculated. Based on their putative prognostic value, EGFR (P(HRR < 1) = .02), AURKA (P(HRR < 1) = .02), VEGFA (P(HRR < 1) = .02), PTGS2 (P(HRR < 1) = .01), SLC2A1 (P(HRR > 1) < 01), HIF1α (P(HRR > 1) = .06), KCNQ1 (P(HRR > 1) = .09), CEA (P (HRR > 1) = .05) and MMP9 (P(HRR < 1) = .07) were included in the CART analysis (n = 201). The resulting classifier was based on AURKA, PTGS2 and MMP9 expression and was associated with OS (HRR 2.79, p < .001), also after multivariate analysis (HRR 3.57, p < .001). The prognostic value of the biomarker-based classifier was superior to the clinicopathological model (p = .001). Prognostic value was highest for colon cancer patients (HRR 5.71, p < .001) and patients not treated with systemic therapy (HRR 3.48, p < .01). Classification based on protein expression in primary tumors could be based on AURKA expression only (HRR 2.59, p = .04). A classifier was generated for patients with CRCLM with improved prognostic value compared to the standard clinicopathological prognostic parameters, which may aid selection of patients who may benefit from adjuvant systemic therapy.

LKB1/STK11 mutations in non-small cell lung cancer patients: Descriptive analysis and prognostic value.

PubMed

Facchinetti, Francesco; Bluthgen, Maria Virginia; Tergemina-Clain, Gabrielle; Faivre, Laura; Pignon, Jean-Pierre; Planchard, David; Remon, Jordi; Soria, Jean-Charles; Lacroix, Ludovic; Besse, Benjamin

2017-10-01

LKB1/STK11 (STK11) is among the most inactivated tumor-suppressor genes in non-small cell lung cancer (NSCLC). While evidence concerning the biologic role of STK11 is accumulating, its prognostic significance in advanced NSCLC has not been envisaged yet. This retrospective analysis included consecutive NSCLC patients with available STK11 information who underwent a platinum-based chemotherapy. STK11 mutational status was correlated to clinico-pathological and mutational features. Kaplan-Meier and Cox models were used for survival curves and multivariate analyses, respectively. Among the 302 patients included, 267 (89%) were diagnosed with stage IIIB/IV NSCLC and 25 (8%) harbored a STK11 mutation (STK11mut). No statistical differences were observed between STK11 status and clinico-pathological variables. We detected a significant correlation between STK11 and KRAS status (p=0.008); among the 25 STK11mut patients, 13 (52%) harbored a concomitant KRAS mutation. Overall survival (OS) was shorter for STK11mut (median OS=10.4months) compared to wild-type patients (STK11wt; median OS=17.3months) in univariate analysis (p=0.085). STK11 status did not impact upon OS in multivariate analysis (p=0.45) and non-significant results were observed for progression-free survival. The co-occurrence of KRAS and STK11 mutations suggest a trend toward detrimental effect in OS (p=0.12). In our cohort enriched for advanced NSCLC patients who received platinum-based chemotherapy, STK11 mutations were not specifically associated with clinico-pathological features and they did not impact upon survival. We confirm the positive correlation between STK11 and KRAS mutations. The co-occurrence of KRAS and STK11 mutations could label a more aggressive molecular subtype of NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinicopathological features of alpha-fetoprotein producing early gastric cancer with enteroblastic differentiation.

PubMed

Matsumoto, Kohei; Ueyama, Hiroya; Matsumoto, Kenshi; Akazawa, Yoichi; Komori, Hiroyuki; Takeda, Tsutomu; Murakami, Takashi; Asaoka, Daisuke; Hojo, Mariko; Tomita, Natsumi; Nagahara, Akihito; Kajiyama, Yoshiaki; Yao, Takashi; Watanabe, Sumio

2016-09-28

To investigate clinicopathological features of early stage gastric cancer with enteroblastic differentiation (GCED). We retrospectively investigated data on 6 cases of early stage GCED and 186 cases of early stage conventional gastric cancer (CGC: well or moderately differentiated adenocarcinoma) who underwent endoscopic submucosal dissection or endoscopic mucosal resection from September 2011 to February 2015 in our hospital. GCED was defined as a tumor having a primitive intestine-like structure composed of cuboidal or columnar cells with clear cytoplasm and immunohistochemical positivity for either alpha-fetoprotein, Glypican 3 or SALL4. The following were compared between GCED and CGC: age, gender, location and size of tumor, macroscopic type, ulceration, depth of invasion, lymphatic and venous invasion, positive horizontal and vertical margin, curative resection rate. Six cases (5 males, 1 female; mean age 75.7 years; 6 lesions) of early gastric cancer with a GCED component and 186 cases (139 males, 47 females; mean age 72.7 years; 209 lesions) of early stage CGC were investigated. Mean tumor diameters were similar but rates of submucosal invasion, lymphatic invasion, venous invasion, and non-curative resection were higher in GCED than CGC (66.6% vs 11.4%, 33.3% vs 2.3%, 66.6% vs 0.4%, 83.3% vs 11% respectively, P < 0.01). Deep submucosal invasion was not revealed endoscopically or by preoperative biopsy. Histologically, in GCED the superficial mucosal layer was covered with a CGC component. The GCED component tended to exist in the deeper part of the mucosa to the submucosa by lymphatic and/or venous invasion, without severe stromal reaction. In addition, Glypican 3 was the most sensitive marker for GCED (positivity, 83.3%), immunohistochemically. Even in the early stage GCED has high malignant potential, and preoperative diagnosis is considered difficult. Endoscopists and pathologists should know the clinicopathological features of this highly malignant type of cancer.

Expression of 17β-hydroxysteroid dehydrogenase type 2 is associated with some clinicopathological features in gastric cancer.

PubMed

Frycz, Bartosz Adam; Murawa, Dawid; Borejsza-Wysocki, Maciej; Marciniak, Ryszard; Murawa, Paweł; Drews, Michał; Jagodziński, Paweł Piotr

2015-03-01

In most populations, gastric cancer (GC) incidence is higher in men than in women, which may suggest the role of sex steroid hormones in gastric cancerogenesis. Both, androgens and estrogens can be synthetised in peripherial tissues. This process is controlled by expression of steroidogenic enzymes. Therefore, we evaluate the 17β-hydroxysteroid dehydrogenase type 2 (HSD17B2) transcript and protein levels in gastric tumoral and nontumoral tissue. We also determined the association between HSD17B2 transcript and protein levels and some clinicopathological features in GC. We found significantly decreased levels of HSD17B2 transcript (P=0.00072) and protein (P=0.00017) in primary tumoral tissues of GC patients, as compared to nontumoral tissues. In patients above 60 years of age the amounts of HSD17B2 transcript (P=0.00044) and protein (P=0.00027) were significantly lower in tumoral than nontumoral tissues. Similarly, lower HSD17B2 levels, both in terms of the transcript and protein, were observed in tumoral tissues of male (P=0.013, P=0.0014), patients stomach (P=0.0062, P=0.045) and cardia (P=0.02, P=0.02) site of tumor, T3 (P=0.018, P=0.014) depth of invasion, N0 (P=0.017, P=0.045) lymph node metastasis, G3 (P=0.0027, P=0.014) malignancy grade. We also observed significantly reduced level of HSD17B2 transcript in tumoral tissue specimens of females (P=0.014), T4 depth of invasion (P=0.02), N3 lymph node metastasis (P=0.037) and G2 malignancy grade (P=0.045). Furthermore, diffuse GC histological types were associated with lower HSD17B2 protein level (P=0.024) than nontumoral tissues. We demonstrated that HSD17B2 transcript and protein levels are linked to some clinicopathological features in GC. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes.

PubMed

La-Touche, Susannah; Lemetre, Christophe; Lambros, Maryou; Stankiewicz, Elzbieta; Ng, Charlotte K Y; Weigelt, Britta; Rajab, Ramzi; Tinwell, Brendan; Corbishley, Cathy; Watkin, Nick; Berney, Dan; Reis-Filho, Jorge S

2016-01-01

Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3-q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents.

DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes

PubMed Central

Lambros, Maryou; Stankiewicz, Elzbieta; Ng, Charlotte K. Y.; Weigelt, Britta; Rajab, Ramzi; Tinwell, Brendan; Corbishley, Cathy; Watkin, Nick; Berney, Dan; Reis-Filho, Jorge S.

2016-01-01

Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3-q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents. PMID:26901676

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

PubMed Central

2012-01-01

Background c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. Methods In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008–2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Results Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed. Conclusions c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429 PMID:22640970

Prognostic value of long non-coding RNA CCAT1 expression in patients with cancer: A meta-analysis.

PubMed

Shi, Deyao; Wu, Fashuai; Gao, Feng; Qing, Xiangcheng; Shao, Zengwu

2017-01-01

LncRNA CCAT1 is significantly overexpressed in various types of cancers, suggesting that it might be associated with prognosis and clinicopathological features in patients with cancer. A comprehensive search was performed in Pubmed, Web of Science, OVID and CNKI databases. We also retrieved articles from other sources, such as retrieving from the reference lists of relevant articles. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value. A total of 1587 patients from 11 eligible studies were included in the meta-analysis. The results showed that high expression level of CCAT1 was significantly associated with shorter overall survival in cancer patients (HR 2.335, 95% CI:1.551-3.517); in the subgroup analysis, region (China or UK), sample size (more or less than 100), type of cancer (digestive or non-digestive disease) and paper quality (score more or less than 7) did not alter the association between CCAT1 expression and cancer prognosis but preoperative treatment did. And CCAT1 expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.195, 95%CI:1.316-3.664) using Cox multivariate analyses. The clinicopathological parameters analysis further showed that increased expression level of CCAT1 was correlated with tumor size, lymph node metastasis, TNM stage, distant metastasis, microvascular invasion and capsular formation in relevant cancers. The meta-analysis results from present study suggested that increased expression level of CCAT1 was associated with poor prognosis and can serve as an independent biomarker. And the expression level of CCAT1 was associated with clinicopathological features in relevant cancers.

EGFR, ALK, RET, KRAS and BRAF alterations in never-smokers with non-small cell lung cancer.

PubMed

Dong, Y U; Ren, Weihong; Qi, Jun; Jin, B O; Li, Ying; Tao, Huiqing; Xu, Ren; Li, Yanqing; Zhang, Qinxian; Han, Baohui

2016-04-01

Non-small cell lung cancer (NSCLC), caused by various mutations in a spectrum of cancer driver genes, may have distinct pathological characteristics and drug responses. Extensive genetic screening and pathological characterization is required for the design of customized therapies to improve patient outcomes. Notably, NSCLC in never-smokers exhibits distinctive clinicopathological features, which are frequently associated with tumorigenic mutations, and thus may be treated as a unique disease entity. However, to the best of our knowledge, these mutations have not been extensively and accurately characterized in an NSCLC study with a large sample size. Therefore, the present study enrolled a large cohort of NSCLC patients, which consisted of 358 never-smokers, for the screening of genetic alterations in the epidermal growth factor receptor (EGFR), ret proto-oncogene (RET), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma viral oncogene homolog (KRAS) and B-Raf proto-oncogene serine/threonine kinase (BRAF) tumorigenic genes. It was identified that the mutation rate was 47.8, 7.5, 3.6, 1.4 and 0.3% for EGFR, ALK, KRAS, RET and BRAF, respectively. In addition, clinicopathological features associated with these mutations were characterized. EGFR mutations were more frequently observed in female and older patients. By contrast, KRAS mutations were more frequently detected in male patients, and ALK and RET translocations in younger patients. The cancer cells were frequently well-differentiated in carcinoma cases exhibiting EGFR mutations, however, were less differentiated in those with ALK translocations. In conclusion, the present study determined the frequency of oncogenic alterations and associated clinicopathological features in NSCLC exhibited by never-smokers using a large sample size. The results of the present study may enrich our knowledge of NSCLC in never-smokers and provide useful insights for improvement of the outcome of molecularly targeted therapies for the treatment of NSCLC.

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays.

PubMed

Sotoudeh, Kambiz; Hashemi, Forough; Madjd, Zahra; Sadeghipour, Alireza; Molanaei, Saadat; Kalantary, Elham

2012-05-28

c-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray. In a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008-2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining. Finally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed. c-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429.

Renal hybrid oncocytic/chromophobe tumors - a review.

PubMed

Hes, Ondrej; Petersson, Fredrik; Kuroda, Naoto; Hora, Milan; Michal, Michal

2013-10-01

Hybrid oncocytic/chromophobe tumors (HOCT) occur in three clinico-pathologic situations; (1) sporadically, (2) in association with renal oncocytomatosis and (3) in patients with Birt-Hogg-Dubé syndrome (BHD). There are no specific clinical symptoms in patients with sporadic or HOCT associated with oncocytosis/oncocytomatosis. HOCT in patients with BHD are usually encountered on characteristic BHD clinicopathologic background. Sporadic HOCT are composed of neoplastic cells with eosinophilic oncocytic cytoplasm. Tumors are usually arranged in a solid-alveolar pattern. Some neoplastic cells may have a perinuclear halo, no raisinoid nuclei are present. HOCT occurring in patients with oncocytomatosis are morphologically identical to sporadic HOCT. HOCT in BHD frequently display 3 morphologic patterns, either in isolation or in combination; (1) An admixture of areas typical of RO and CHRCC, respectively, (2) Scattered chromophobe cells in the background of a typical RO, (3) Large eosinophilic cells with intracytoplasmic vacuoles. The immunohistochemical profiles of HOCT in all clinicopathologic and morphologic groups differ slightly. The majority of tumors express parvalbumin, antimitochondrial antigen and CK 7. CD117 is invariably positive. HOCT show significant molecular genetic heterogeneity. The highest degree of variability in numerical chromosomal changes is present in sporadic HOCT. HOCT in the setting of oncocytomatosis have revealed a lesser degree of variability in the chromosomal numerical aberrations. HOCT in patients with BHD display FLCN gene mutations, which are absent in the other groups. HOCT (all three clinicopathologic groups) seem to behave indolently, as no evidence of aggressive behavior has been documented. However, no report with follow up longer than 10 years has been published.

The ratio of hemoglobin to red cell distribution width as a novel prognostic parameter in esophageal squamous cell carcinoma: a retrospective study from southern China

PubMed Central

Bi, Xiwen; Yang, Hang; An, Xin; Wang, Fenghua; Jiang, Wenqi

2016-01-01

Background We propose a novel prognostic parameter for esophageal squamous cell carcinoma (ESCC)—hemoglobin/red cell distribution width (HB/RDW) ratio. Its clinical prognostic value and relationship with other clinicopathological characteristics were investigated in ESCC patients. Results The optimal cut-off value was 0.989 for the HB/RDW ratio. The HB/RDW ratio (P= 0.035), tumor depth (P = 0.020) and lymph node status (P<0.001) were identified to be an independent prognostic factors of OS by multivariate analysis, which was validated by bootstrap resampling. Patients with a low HB/RDW ratio had a 1.416 times greater risk of dying during follow-up compared with those with a high HB/RDW (95% CI = 1.024–1.958, P = 0.035). Materials and Methods We retrospectively analyzed 362 patients who underwent curative treatment at a single institution between January 2007 and December 2008. The chi-square test was used to evaluate relationships between the HB/RDW ratio and other clinicopathological variables; the Kaplan–Meier method was used to analyze the 5-year overall survival (OS); and the Cox proportional hazards models were used for univariate and multivariate analyses of variables related to OS. Conclusion A significant association was found between the HB/RDW ratio and clinical characteristics and survival outcomes in ESCC patients. Based on these findings, we believe that the HB/RDW ratio is a novel and promising prognostic parameter for ESCC patients. PMID:27223088

The importance of consumption of the epidermis in malignant melanoma and correlation with clinicopathological prognostic parameters.

PubMed

Seçkin, Selda; Ozgũn, Elmas

2011-01-01

The aim of the study was to investigate the importance of consumption of the epidermis as an additional diagnostic criteria for malignant melanoma and to evaluate its relationship to clinicopathological findings. The age, gender, localization of the lesion and the histopathological parameters such as tumor type, Breslow thickness, ulceration, Clark's level, mitosis/mm2, lymphocytic infiltration were noted in 40 malignant melanoma cases. Consumption of the epidermis was evaluated in tumor sections. Consumption of the epidermis (COE) due to thinning of the epidermis and loss of rete ridges was noted as (+) or (-). Furthermore, COE was compared with clinical and histopathological parameters. The Shapiro Wilk and Logistic Regression tests were used for statistical analysis. The results were accepted as significant if the p value was < 0.05. COE was detected in 60% (24/40) of malignant melanoma cases. A positive correlation was present between COE and head and neck localization (p = 0,698), superficial spreading melanoma (p = 0,341), ulceration (p = 0,097) and brisk lymphocytic infiltration (p = 0,200) but the results were not statistically significant. COE was frequently detected in males but the difference was not statistically significant (p = 0.796). There was no correlation or significant statistical association between COE and age, Breslow thickness, Clark's level or the mitotic index. The detection of COE in most of the patients suggests that COE could be a histopathological criterion in the diagnosis of malignant melanoma. The frequent association between COE and the presence of ulceration could also direct attention to COE as regards prognostic importance.

Clinicopathological, functional, and immediate oncologic outcome assessment in men aged≤50 years with prostate cancer after robotic prostatectomy.

PubMed

Samadi, David B; Sebrow, Dov; Hobbs, Adele R; Bernstein, Adrien N; Brajtbord, Jonathan; Lavery, Hugh J; Jazayeri, Seyed Behzad

2017-01-01

To define the pathologic and functional outcomes of men 50 years of age and younger with prostate cancer in a contemporary robotic cohort, this study was designed. Patients undergoing robotic-assisted laparoscopic prostatectomy from April 2002 to April 2012 (n = 2,495) formed the base population for the current analyses. The patients were dichotomized according to their age≤50 (n = 271) and>50-year-old (n = 2,224). Clinicopathological and health-related quality-of-life outcomes were recorded and analyzed for differences. Propensity score matching was used when assessing urinary and sexual function outcome. Baseline prostate-specific antigen and clinical stage were similar between men older than 50 years and those younger. Younger patients had less severe disease (D׳Amico risk and Gleason scores) and smaller prostates. Young men had higher rates of erectile function at all time points, including baseline (94% vs. 83% at 12mo, P <0.01). Continence was similar at all time points except for 6 months, where younger patients experienced a faster return than older patients and then remained constant, while older patients continued to improve (96% vs. 89%, P<0.01). After matching process, the difference in erectile function at 6-month follow-up was lost. Most men aged 50 years and younger who received robotic-assisted laparoscopic prostatectomy had clinically significant prostate cancer. Although histopathologic and short-term oncologic outcomes were nearly identical when compared to older patients, younger men had a more rapid and superior return of erectile function. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical significance of preoperative and postoperative cytokeratin 19 messenger RNA level in peripheral blood of esophageal cancer patients.

PubMed

Qiao, Y-F; Chen, C-G; Yue, J; Ma, Z; Yu, Z-T

2016-11-01

The purpose of this study is to analyze the correlation between preoperative/postoperative Cytokeratin 19 (CK19) messenger RNA (mRNA) level in peripheral blood (PB) and the clinical significance in esophageal cancer patients with different clinicopathological factors. We detected the preoperative and postoperative CK19 mRNA level in the PB of 139 esophageal cancer patients who underwent complete resection and evaluated its clinical significance. We found that both the preoperative and postoperative CK19 mRNA level increased in the esophageal cancer patients with lymph node metastasis, relapse or distant metastasis compared with that in cancers without lymph node metastasis, relapse or distant metastasis. High postoperative CK19 mRNA levels indicate a short disease-free survival (DFS) for the whole cohort esophageal cancer patients, whereas the high preoperative CK19 mRNA levels only indicate a short DFS for the esophageal cancer patients with squamous cell carcinoma, TNM III stage, and lymph node metastasis. The dynamic change of CK19 mRNA levels could indicate the prognosis of esophageal cancer patients. The patients with decreasing CK19 mRNA level after surgery had good prognosis, and the patients with changeless CK19 mRNA level had poor prognosis. Taken together, CK19 mRNA levels could be a promising marker in assessing prognosis or assigning treatment for the esophageal cancer patients according to different clinicopathological factors. © 2015 International Society for Diseases of the Esophagus.

Incidence and survival differences in esophageal cancer among ethnic groups in the United States

PubMed Central

Chen, Zheling; Ren, Yinghong; Du, Xianglin L; Yang, Jiao; Shen, Yanwei; Li, Shuting; Wu, Yunying; Lv, Meng; Dong, Danfeng; Li, Enxiao; Li, Wei; Liu, Peijun; Yang, Jin; Yi, Min

2017-01-01

Objectives This study was performed to identify the differences in incidence, clinicopathological features, and survival in esophageal cancer among ethnic groups in the United States and to determine the reasons for the differences. Result A total of 49,766 patients were included. Black and Asian groups had a higher proportion of squamous cell carcinoma (ESCC) (85.5% and 75.4%, respectively) and mid-esophagus tumor (43.2% and 37.7% respectively) than the non-Hispanic white and Hispanic white groups. The incidences of ESCC in all ethnic groups declined since 1973, especially in black males. At the same time, incidences of esophageal adenocarcinoma (EAC) dramatically increased in white males since 1973. And incidences of ESCC and EAC were the lowest and stable in Asian female. Multivariable models showed that patients who were male, or black, or had larger tumors, or positive lymph nodes had an increased risk of death from esophageal cancer, while patients with ESCC or diagnosed after 2005 or treated with surgery had a lower likelihood of death. For ESCC, the black patients had the lowest DSS, while for EAC there were no significant differences in DSS among the ethnic/racial groups. Materials and Method From the Surveillance, Epidemiology, and End Results Program database, patients diagnosed with esophageal cancer from 1998-2013 were identified. Differences in incidences, clinicopathological features, treatments, and disease-specific survival (DSS) in four broad racial/ethnic groups were compared. Conclusion Histological type distribution between racial groups could be an important consideration in the incidence and the survival trend but other factors could also have an effect. PMID:28410201

Incidence and survival differences in esophageal cancer among ethnic groups in the United States.

PubMed

Chen, Zheling; Ren, Yinghong; Du, Xianglin L; Yang, Jiao; Shen, Yanwei; Li, Shuting; Wu, Yunying; Lv, Meng; Dong, Danfeng; Li, Enxiao; Li, Wei; Liu, Peijun; Yang, Jin; Yi, Min

2017-07-18

This study was performed to identify the differences in incidence, clinicopathological features, and survival in esophageal cancer among ethnic groups in the United States and to determine the reasons for the differences. A total of 49,766 patients were included. Black and Asian groups had a higher proportion of squamous cell carcinoma (ESCC) (85.5% and 75.4%, respectively) and mid-esophagus tumor (43.2% and 37.7% respectively) than the non-Hispanic white and Hispanic white groups. The incidences of ESCC in all ethnic groups declined since 1973, especially in black males. At the same time, incidences of esophageal adenocarcinoma (EAC) dramatically increased in white males since 1973. And incidences of ESCC and EAC were the lowest and stable in Asian female. Multivariable models showed that patients who were male, or black, or had larger tumors, or positive lymph nodes had an increased risk of death from esophageal cancer, while patients with ESCC or diagnosed after 2005 or treated with surgery had a lower likelihood of death. For ESCC, the black patients had the lowest DSS, while for EAC there were no significant differences in DSS among the ethnic/racial groups. From the Surveillance, Epidemiology, and End Results Program database, patients diagnosed with esophageal cancer from 1998-2013 were identified. Differences in incidences, clinicopathological features, treatments, and disease-specific survival (DSS) in four broad racial/ethnic groups were compared. Histological type distribution between racial groups could be an important consideration in the incidence and the survival trend but other factors could also have an effect.

Preoperative subclinical hypothyroidism in patients with papillary thyroid carcinoma.

PubMed

Ahn, Dongbin; Sohn, Jin Ho; Kim, Jae Hyug; Shin, Chang Min; Jeon, Jae Han; Park, Ji Young

2013-01-01

To assess the effect of preoperative subclinical hypothyroidism on prognosis and on the tumour's clinicopathological features at initial diagnosis of papillary thyroid carcinoma (PTC). 328 patients who underwent surgery for PTC between January 2001 and December 2006 were enrolled in this study. Of these, we compared 35 patients with preoperative subclinical hypothyroidism with 257 patients who were euthyroid before the operation, with respect to clinicopathological characteristics and prognosis. No significant differences were observed in tumour size, extrathyroidal extension, and multifocality between subclinical hypothyroidism and euthyroid patients. Patients with subclinical hypothyroidism had a considerably lower percentage of lymph node metastasis than did euthyroid patients (8.6% vs. 21.8%, p=0.068). Although preoperative subclinical hypothyroidism decreased the risk of lymph node metastasis at 0.313 of odds ratio in the multivariate analysis, its significance was not verified (95% confidence internal, 0.089-1.092; p=0.068). Patients with preoperative subclinical hypothyroidism tended to have a better prognosis than did preoperative euthyroid patients, for both recurrence (2.9% vs. 14.0%, p=0.099) and 7-year disease-free survival (97.1% vs. 87.8%, p=0.079), during the 82-month mean follow-up period. However, even as thyroid-stimulating hormone (TSH) concentration increased, there were no consistent relationships observed between the TSH levels and the prognostic parameters. We could find neither a consistent positive nor a negative linear relationship between TSH levels and several prognostic parameters, indicating that subclinical hypothyroidism with elevated TSH is not an independent predictor of tumour aggressiveness and poor prognosis in PTC. Copyright © 2013 Elsevier Inc. All rights reserved.

High CHMP4B expression is associated with accelerated cell proliferation and resistance to doxorubicin in hepatocellular carcinoma.

PubMed

Hu, Baoying; Jiang, Dawei; Chen, Yuyan; Wei, Lixian; Zhang, Shusen; Zhao, Fengbo; Ni, Runzhou; Lu, Cuihua; Wan, Chunhua

2015-04-01

Charged multivesicular body protein 4B (CHMP4B), a subunit of the endosomal sorting complex required for transport (ESCRT)-III complex, plays an important part in cytokinetic membrane abscission and the late stage of mitotic cell division. In this study, we explored the prognostic significance of CHMP4B in human hepatocellular carcinoma (HCC) and its impact on the physiology of HCC cells. Western blot and immunohistochemistrical analyses showed that CHMP4B was significantly upregulated in HCC tissues, compared with adjacent non-tumorous tissues. Meanwhile, clinicopathological analysis revealed that high CHMP4B expression was correlated with multiple clinicopathological variables, including AFP, cirrhosis, AJCC stage, Ki-67 expression, and poor prognosis. More importantly, univariate and multivariate survival analyses demonstrated that CHMP4B served as an independent prognostic factor for survival of HCC patients. Using HCC cell cultures, we found that the expression of CHMP4B was progressively upregulated after the release from serum starvation. To verify whether CHMP4B could regulate the proliferation of HCC cells, CHMP4B was knocked down through the transfection of CHMP4B-siRNA oligos. Flow cytometry and CCK-8 assays indicated that interference of CHMP4B led to cell cycle arrest and proliferative impairment of HCC cells. Additionally, depletion of CHMP4B expression could increase the sensitivity to doxorubicin in HepG2 and Huh7 cells. Taken together, our results implied that CHMP4B could be a promising prognostic biomarker as well as a potential therapeutic target of HCC.

Cystoisospora belli Infection of the Gallbladder in Immunocompetent Patients: A Clinicopathologic Review of 18 Cases.

PubMed

Lai, Keith K; Goyne, Hannah E; Hernandez-Gonzalo, David; Miller, Kennon A; Tuohy, Marion; Procop, Gary W; Lamps, Laura W; Patil, Deepa T

2016-08-01

Cystoisospora belli, previously known as Isospora belli, is an obligate intracellular coccidian parasite that is most often associated with gastrointestinal disease in immunocompromised patients. In this study, we detail the clinicopathologic features of 18 cases of Cystoisospora infection affecting the gallbladder in immunocompetent individuals and compare them with a control group. Each case was reviewed for cholecystitis (none, acute, chronic), epithelial disarray, presence of intraepithelial lymphocytes (none, rare [≤5 per 20 epithelial cells], present [>5 per 20 epithelial cells]), architectural distortion, intramucosal eosinophilia, and mural thickening/serositis. The mean age of patients with Cystoisospora infection was 33 years and the male to female ratio 1:4.3. Cholecystectomy was performed for biliary dyskinesia (n=7), abdominal pain (n=7), suspected cholelithiasis (n=5), and cholecystitis (n=3). In 2 cases, Cystoisospora was found in donor gallbladders resected at the time of liver transplantation. Each case was characterized by eosinophilic, oval or banana-shaped intraepithelial parasites within perinuclear parasitophorous vacuoles. Most cases showed epithelial disarray and minimal intraepithelial lymphocytosis. Of the 11 cases with an average follow-up of 15 months, none had evidence of disease related to Cystoisospora infection within the biliary tract or elsewhere in the gastrointestinal tract. We present the largest series of gallbladder cystoisosporiasis in immunocompetent patients to date. Cystoisospora infection is underrecognized in the gallbladders of immunocompetent patients, in part due to the subtle findings in routine cholecystectomy specimens. On the basis of the clinical follow-up, gallbladder cystoisosporiasis in immunocompetent individuals appears to be a self-limited infection.

High expression of atypical protein kinase C lambda/iota in gastric cancer as a prognostic factor for recurrence.

PubMed

Takagawa, Ryo; Akimoto, Kazunori; Ichikawa, Yasushi; Akiyama, Hirotoshi; Kojima, Yasuyuki; Ishiguro, Hitoshi; Inayama, Yoshiaki; Aoki, Ichiro; Kunisaki, Chikara; Endo, Itaru; Nagashima, Yoji; Ohno, Shigeo

2010-01-01

The atypical protein kinase C lambda/iota (aPKClambda/iota) is involved in several signal transduction pathways that influence cell growth, apoptosis, and the establishment and maintenance of epithelial cell polarity. Overexpression of aPKClambda/iota has been reported in several cancers and been shown to be associated with oncogenesis. However, the expression and role of aPKClambda/iota in gastric cancer, one of the commonest cancers in Asia, have not so far been investigated. This study aimed to clarify the relationship between aPKClambda/iota expression and the clinicopathological features of gastric cancer. Gastric adenocarcinoma samples were obtained from 177 patients who underwent gastrectomy at the Yokohama City University Hospital between 1999 and 2004. Expression of aPKClambda/iota and E: -cadherin was examined immunohistochemically and compared with clinicopathological features of the tumors. Univariate and multivariate analyses were performed for both disease-specific and relapse-free survival. Overexpression of aPKClambda/iota protein was detected in 126 of the 177 (71.2%) gastric cancers. Immunohistological staining for aPKClambda/iota was stronger in gastric adenocarcinoma of intestinal type than diffuse type (p = 0.036), but was not correlated with E: -cadherin expression. A multivariate analysis suggested that nodal metastasis and aPKClambda/iota overexpression were prognostic factors for disease recurrence. Our results suggested that aPKClambda/iota overexpression was a strong prognostic factor for gastric adenocarcinoma recurrence. As well as being a new prognostic indicator, aPKClambda/iota is also likely to be a novel therapeutic target for gastric cancer.

Clinicopathological, endoscopic, and molecular characteristics of the "skirt" - a new entity of lesions at the margin of laterally spreading tumors.

PubMed

Osera, Shozo; Fujii, Satoshi; Ikematsu, Hiroaki; Miyamoto, Hideaki; Oono, Yasuhiro; Yano, Tomonori; Ochiai, Atsushi; Yoshino, Takayuki; Ohtsu, Atsushi; Kaneko, Kazuhiro

2016-05-01

A slightly elevated flat lesion with wide pits has occasionally been observed at the margin of laterally spreading tumors (LSTs) and is known as a "skirt." The aim of this study was to evaluate the clinicopathological, endoscopic, and genetic characteristics of a skirt. Consecutive LSTs were examined to evaluate the pathological, endoscopic, and genetic characteristics. Pathological characteristics, including the dimension of the cryptic opening (DCO), width of the individual gland (WIG), DCO to WIG ratio, and microvessel diameter were elucidated and compared with those of hyperplastic polyps, low grade dysplasia (LGD), and normal mucosa. The endoscopic findings of pit and microvascular patterns were assessed. Gene mutation analyses were performed for the KRAS, BRAF, NRAS, and PIK3CA genes. A skirt was identified in 35 of 1023 LSTs, and 80 % of lesions with a skirt had a component of either intramucosal or submucosal adenocarcinoma. The DCO, WIG, and DCO to WIG ratio of the skirt were significantly larger than those of other lesions. The microvessel diameters in skirts were significantly smaller than those in LGDs. Regarding the endoscopic findings, 30 skirts showed pits with a coral reef-like appearance, and all skirt regions were found to have a type I capillary pattern. KRAS mutation at codon 146 was found in the nodular part in one of five LSTs with a skirt. The skirt is a newly identified lesion distinct from hyperplastic polyps and LGDs, suggesting the presence of a novel pathway for rectal carcinogenesis from LSTs with a skirt. © Georg Thieme Verlag KG Stuttgart · New York.

The relationship between components of tumour inflammatory cell infiltrate and clinicopathological factors and survival in patients with primary operable invasive ductal breast cancer

PubMed Central

Mohammed, Z MA; Going, J J; Edwards, J; Elsberger, B; Doughty, J C; McMillan, D C

2012-01-01

Background: The importance of the components of host local inflammatory response in determining outcome in primary operable ductal invasive breast cancer is not clear. The aim of this study was to examine the relationship between components of the tumour inflammatory cell infiltrate and standard clinicopathological factors including hormone status (oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER)-2), Ki-67 and survival in patients with primary operable invasive ductal breast cancer. Methods: Tumour inflammatory cell infiltrate, hormone status (ER, PR and HER-2), Ki-67 and standard clinicopathological factors were determined using routine pathological and immuno-histochemical techniques in 468 patients. Results: The large majority (94%) of ductal tumours had evidence of inflammatory cell infiltrate. The general inflammatory cell infiltrate was positively associated with high grade (P<0.001), the absence of ER (P<0.001), the absence of PR (P<0.01), the presence of vascular invasion (P<0.05) and high lymphocytic infiltrate, plasma cell infiltrate, other inflammatory cell infiltrate and macrophage infiltrate (all P<0.001). The median follow-up of the survivors was 165 months. During this period, 93 patients died of their cancer. On univariate analysis, stratified for ER status, tumour size (P<0.01), lymph node involvement (P<0.001), tumour plasma cell infiltrate (P<0.001), other inflammatory cell infiltrate (P<0.05) and treatment (P<0.05) were associated with poorer cancer-specific survival whereas lymphocyte infiltrate (P<0.001) was associated with improved cancer-specific survival. On multivariate analysis, stratified for ER status, lymph node involvement (P<0.05) was independently associated with poorer cancer-specific survival whereas increased tumour lymphocyte infiltrate (P<0.001) was independently associated with improved cancer-specific survival. Conclusion: The results of this study show that, using routine histology, the general inflammatory cell infiltrate was a common feature and was positively associated with high grade, the absence of ER, the absence of PR, the presence of vascular invasion and high-grade infiltration of lymphocytes, plasma cells, other inflammatory cells and macrophages. Also, that within a mature cohort of patients, a high lymphocytic infiltrate was associated with improved survival, independent of clinicopathological characteristics including ER status, in primary operable ductal invasive breast cancer. These results rationalise previous work and provide a sound basis for future studies in this important area of breast cancer research. PMID:22878371

The Stillbirth Classification System for the Safe Passage Study: Incorporating Mechanism, Etiology, and Recurrence

PubMed Central

Boyd, Theonia K.; Wright, Colleen A.; Odendaal, Hein J.; Elliott, Amy J.; Sens, Mary Ann; Folkerth, Rebecca D.; Roberts, Drucilla J.; Kinney, Hannah C.

2017-01-01

OBJECTIVE Describe the classification system for the assignment of the cause of death for stillbirth in the Safe Passage Study, an international, multi-institutional, prospective analysis conducted by the NIAAA/NICHD funded PASS Network (The Prenatal Alcohol in SIDS and Stillbirth (PASS) Research Network). The study mission is to determine the role of prenatal alcohol and/or cigarette smoke exposure in adverse pregnancy outcomes, including stillbirth, in a high-risk cohort of 12,000 maternal/fetal dyads. METHODS The PASS Network classification system is based upon 5 ‘sites of origin’ for cause of stillbirth (Fetal, Placental, Maternal, External/Environmental, or Undetermined), further subdivided into mechanism subcategories (e.g., Placental Perfusion Failure). Both site of origin and mechanism stratification are employed to assign an ultimate cause of death. Each PASS stillbirth (n=19) in the feasibility study was assigned a cause of death, and status of sporadic versus recurrent. Adjudication involved review of the maternal and obstetrical records, and fetal autopsy and placental findings, with complete consensus in each case. Two published classification systems, i.e., INCODE and ReCoDe, were used for comparison. RESULTS Causes of stillbirth classified were: fetal (n=5, 26%), placental (n=10, 53%), external (n=1, 5%), and undetermined (n=3, 16%). Nine cases (47%) had placental causes of death due to maternal disorders that carry recurrence risks. There was complete agreement for the cause of death across the three classification systems in 26% of cases, and a combination of partial or complete agreement in 68% of cases. Complete vs. partial agreements were predicated upon the classification schemes used for comparison. CONCLUSIONS The proposed PASS system is a user-friendly classification system that provides comparable information to previously published systems. Advantages include its simplicity, mechanistic formulations, tight clinicopathologic integration, provision for an undetermined category, and its wide applicability for use by perinatal mortality review boards with access to information routinely collected during clinicopathologic evaluations. PMID:27116324

Napoleon Bonaparte's gastric cancer: a clinicopathologic approach to staging, pathogenesis, and etiology.

PubMed

Lugli, Alessandro; Zlobec, Inti; Singer, Gad; Kopp Lugli, Andrea; Terracciano, Luigi M; Genta, Robert M

2007-01-01

Numerous hypotheses on the cause of Napoleon Bonaparte's death have been proposed, including hereditary gastric cancer, arsenic poisoning, and inappropriate medical treatment. We aimed to determine the etiology and pathogenesis of Napoleon's illness by a comparison of historical information with current clinicopathologic knowledge. Evaluation of Napoleon's clinical history, original autopsy reports, and of historical documents. The clinicopathologic data from 135 gastric cancer patients were used for comparison with the data available on Napoleon. At least T3N1M0 (stage IIIA) gastric cancer. Napoleon's tumor extended from the cardia to the pylorus (>10 cm) without infiltration of adjacent structures, which provides strong evidence for at least stage T3. The N1 stage was determined by the presence of several enlarged and hardened regional (perigastric) lymph nodes, and the M0 stage by the absence of distant metastasis. Analysis of the available historical documents indicates that Napoleon's main risk factor might have been Helicobacter pylori infection rather than a familial predisposition. Our analysis suggests that Napoleon's illness was a sporadic gastric carcinoma of advanced stage. Patients with such tumors have a notoriously poor prognosis.

[Clinico-pathologic Characteristics of Adult Patients with Atypical Infectious Mononucleosis].

PubMed

Yu, Ya-Ping; Song, Ping; An, Zhi-Ming; Zhou, Xiao-Gang; Li, Feng; Wang, Li-Ping; Mei, Jian-Gang; Zhai, Yong-Ping

2016-12-01

To investigate the clinicopathologic characteristics of adult patients with atypical infectious mononucleosis(IM). From January 2003 to December 2013, a total of 5 cases of atypical IM misdiagnosed as lymphoma were selected, and the clinico-pathological characteristics and efficacy of treatment were analyzed. Biopsy of lymph node or tonsil was performed to evaluate the possibility of lymphoma. Peripheral blood EBV antibody and EBV-DNA were examined by ELISA and real-time fluorescence quantitative PCR, respectively. All the cases were considered as lymphoma on the basis of morphological features in initial evaluation before relapse. These features included a florid immunoblastic proliferation, distortion of the underlying nodal or tonsillar architecture and the presence of necrosis. The immunophenotypic features, EBV encoded RNA (EBER) in situ hybridization and the gene rearrangement of immunoglobulin or T cell receptor may be helpful for the distinction of atypical IM from lymphoma. IM as EBV-related lymphoproliferative process shows marked clinical and histological diversity. Atypical case of IM may mimic many different type of lymphoma in clinical and pathologic features, and the misdiagnosis should be avoided by using molecular and pathological examination.

[Gene expression of H-FABP and FAS and its clinicopathological significance in breast infiltrating ductal carcinoma].

PubMed

Li, Hua; Lü, Qing; Xue, Hui; Dong, Li-hua; Yang, Hui-jun

2008-07-01

To detect the expression of Heart or Muscle Fatty acid binding protein (H-FABP) and fatty acid synthase (FAS) in human breast cancer cells. The expression levels of FAS and H-FABP in 81 ductal infiltrating carcinoma (DIC) were detected by RT-PCR, immunohistochemistry and Western blot analysis. The possible associations of the expression of the two proteins with major clinicopathological factors were analyzed. The expression of both H-FABP and FAS increased in DIC cells than in adjacent normal cells. But less H-FABP and FAS were found in grade III DIC than in grade I and grade II DIC (P < 0.05). There was a positive correlation between the expression of H-FABP and FAS. No correlations between the expressions of two genes with other clinicopathological factors were found. The higher expression of H-FABP in grade I and II DIC suggests an early increased response to the over-expression of FAS. The parallel increase of H-FABP and FAS expressions marks increased breast cancer risk.

Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer

PubMed Central

Yamoah, Kosj; Johnson, Michael H.; Choeurng, Voleak; Faisal, Farzana A.; Yousefi, Kasra; Haddad, Zaid; Ross, Ashley E.; Alshalafa, Mohammed; Den, Robert; Lal, Priti; Feldman, Michael; Dicker, Adam P.; Klein, Eric A.; Davicioni, Elai; Rebbeck, Timothy R.; Schaeffer, Edward M.

2015-01-01

Purpose We studied the ethnicity-specific expression of prostate cancer (PC) –associated biomarkers to evaluate whether genetic/biologic factors affect ethnic disparities in PC pathogenesis and disease progression. Patients and Methods A total of 154 African American (AA) and 243 European American (EA) patients from four medical centers were matched according to the Cancer of the Prostate Risk Assessment postsurgical score within each institution. The distribution of mRNA expression levels of 20 validated biomarkers reported to be associated with PC initiation and progression was compared with ethnicity using false discovery rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models. A conditional logistic regression model was used to evaluate the interaction between ethnicity and biomarkers for predicting clinicopathologic outcomes. Results Of the 20 biomarkers examined, six showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04). Dysregulation of AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) as well as loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P = .037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner. Dysregulation of GOLM1 (P = .037), SRD5A2 (P = .023), and MKi67 (P = .023) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years. A greater proportion of AA men than EA men had triple-negative (ERG-negative/ETS-negative/SPINK1-negative) disease (51% v 35%; P = .002). Conclusion We have identified a subset of PC biomarkers that predict the risk of clinicopathologic outcomes in an ethnicity-dependent manner. These biomarkers may explain in part the biologic contribution to ethnic disparity in PC outcomes between EA and AA men. PMID:26195723

Novel Biomarker Signature That May Predict Aggressive Disease in African American Men With Prostate Cancer.

PubMed

Yamoah, Kosj; Johnson, Michael H; Choeurng, Voleak; Faisal, Farzana A; Yousefi, Kasra; Haddad, Zaid; Ross, Ashley E; Alshalafa, Mohammed; Den, Robert; Lal, Priti; Feldman, Michael; Dicker, Adam P; Klein, Eric A; Davicioni, Elai; Rebbeck, Timothy R; Schaeffer, Edward M

2015-09-01

We studied the ethnicity-specific expression of prostate cancer (PC) -associated biomarkers to evaluate whether genetic/biologic factors affect ethnic disparities in PC pathogenesis and disease progression. A total of 154 African American (AA) and 243 European American (EA) patients from four medical centers were matched according to the Cancer of the Prostate Risk Assessment postsurgical score within each institution. The distribution of mRNA expression levels of 20 validated biomarkers reported to be associated with PC initiation and progression was compared with ethnicity using false discovery rate, adjusted Wilcoxon-Mann-Whitney, and logistic regression models. A conditional logistic regression model was used to evaluate the interaction between ethnicity and biomarkers for predicting clinicopathologic outcomes. Of the 20 biomarkers examined, six showed statistically significant differential expression in AA compared with EA men in one or more statistical models. These include ERG (P < .001), AMACR (P < .001), SPINK1 (P = .001), NKX3-1 (P = .03), GOLM1 (P = .03), and androgen receptor (P = .04). Dysregulation of AMACR (P = .036), ERG (P = .036), FOXP1 (P = .041), and GSTP1 (P = .049) as well as loss-of-function mutations for tumor suppressors NKX3-1 (P = .025) and RB1 (P = .037) predicted risk of pathologic T3 disease in an ethnicity-dependent manner. Dysregulation of GOLM1 (P = .037), SRD5A2 (P = .023), and MKi67 (P = .023) predicted clinical outcomes, including 3-year biochemical recurrence and metastasis at 5 years. A greater proportion of AA men than EA men had triple-negative (ERG-negative/ETS-negative/SPINK1-negative) disease (51% v 35%; P = .002). We have identified a subset of PC biomarkers that predict the risk of clinicopathologic outcomes in an ethnicity-dependent manner. These biomarkers may explain in part the biologic contribution to ethnic disparity in PC outcomes between EA and AA men. © 2015 by American Society of Clinical Oncology.

Quantitative Profiling of Colorectal Cancer-Associated Bacteria Reveals Associations between Fusobacterium spp., Enterotoxigenic Bacteroides fragilis (ETBF) and Clinicopathological Features of Colorectal Cancer

PubMed Central

Viljoen, Katie S.; Dakshinamurthy, Amirtha; Goldberg, Paul; Blackburn, Jonathan M.

2015-01-01

Various studies have presented clinical or in vitro evidence linking bacteria to colorectal cancer, but these bacteria have not previously been concurrently quantified by qPCR in a single cohort. We quantify these bacteria (Fusobacterium spp., Streptococcus gallolyticus, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Enteropathogenic Escherichia coli (EPEC), and afaC- or pks-positive E. coli) in paired tumour and normal tissue samples from 55 colorectal cancer patients. We further investigate the relationship between a) the presence and b) the level of colonisation of each bacterial species with site and stage of disease, age, gender, ethnicity and MSI-status. With the exception of S. gallolyticus, we detected all bacteria profiled here in both tumour and normal samples at varying frequencies. ETBF (FDR = 0.001 and 0.002 for normal and tumour samples) and afaC-positive E. coli (FDR = 0.03, normal samples) were significantly enriched in the colon compared to the rectum. ETBF (FDR = 0.04 and 0.002 for normal and tumour samples, respectively) and Fusobacterium spp. (FDR = 0.03 tumour samples) levels were significantly higher in late stage (III/IV) colorectal cancers. Fusobacterium was by far the most common bacteria detected, occurring in 82% and 81% of paired tumour and normal samples. Fusobacterium was also the only bacterium that was significantly higher in tumour compared to normal samples (p = 6e-5). We also identified significant associations between high-level colonisation by Fusobacterium and MSI-H (FDR = 0.05), age (FDR = 0.03) or pks-positive E. coli (FDR = 0.01). Furthermore, we exclusively identified atypical EPEC in our cohort, which has not been previously reported in association with colorectal cancer. By quantifying colorectal cancer-associated bacteria across a single cohort, we uncovered inter- and intra-individual patterns of colonization not previously recognized, as well as important associations with clinicopathological features, especially in the case of Fusobacterium and ETBF. PMID:25751261

Prospective evaluation of the acute patient physiologic and laboratory evaluation score and an extended clinicopathological profile in dogs with systemic inflammatory response syndrome.

PubMed

Giunti, Massimo; Troia, Roberta; Bergamini, Paolo Famigli; Dondi, Francesco

2015-01-01

To investigate the prognostic value of the acute patient physiologic and laboratory evaluation (APPLE) score and relevant clinicopathological markers in dogs with systemic inflammatory response syndrome (SIRS). Prospective observational cohort study. Veterinary teaching hospital. Thirty-three dogs with SIRS admitted to the intensive care unit (ICU) were compared to 35 healthy control dogs. Dogs with SIRS were divided into septic (n = 20) and nonseptic (n = 13) etiologies and as survivors (alive to discharge, n = 22) and nonsurvivors (n = 11: died, n = 6, or humanely euthanized, n = 5). For all dogs, physiological and laboratory parameters were prospectively collected for the calculation of the APPLE fast score. No difference between septic and nonseptic SIRS dogs was detected for any parameter evaluated. Survivors had significantly higher total protein, albumin concentrations, antithrombin activity (ATA), and base excess (BE), as well as significantly lower lactate, urea, creatinine concentrations, urinary protein to creatinine ratio and APPLE fast score compared to nonsurvivors. Higher values of creatinine, lactate, anion gap, alanine transaminase (ALT), and APPLE fast score were significantly associated with an increased risk of death in SIRS dogs, while higher values of total protein, albumin, ATA, and BE were associated with a significantly reduced risk of mortality. When a multivariate binary logistic regression analysis was performed, the APPLE fast score was the only significant parameter retained. The determination of the APPLE fast score in clinical setting, as well as the measurement of APP, ATA, lactate, BE, anion gap, ALT, urinary proteins, and electrolytes may be beneficial for a better assessment of dogs with SIRS. Identified parameters were significantly related with the presence of SIRS and their evaluation should be considered for the assessment of disease severity, and guidance of the decision-making process in critically ill dogs. © Veterinary Emergency and Critical Care Society 2014.

Role of RANK and Akt1 activation in human osteosarcoma progression: A clinicopathological study.

PubMed

Zhu, Jianxi; Liu, Yuwei; Zhu, Yong; Zeng, Min; Xie, Jie; Lei, Pengfei; Li, Kanghua; Hu, Yihe

2017-06-01

The receptor activator of nuclear factor κB (RANK) axis is the fundamental signaling pathway in bone formation as well as bone tumor pathophysiology. The aim of the present study was to evaluate the impact of the expression of RANK and its downstream signaling molecule Akt1 on tumor progression in patients with osteosarcoma. Expression of RANK and Akt1 was examined in 78 human osteosarcoma samples by immunohistochemistry using formalin-fixed samples. Following this, each graded immunohistochemistry result was correlated with clinicopathological parameters and patient survival. In total, 60 osteosarcomas (76.9%) expressed RANK and 58 cases (74.4%) showed expression of Akt1. In addition, expression of RANK was negatively correlated with disease-free survival by Kaplan-Meier analysis. A resistance was observed to chemotherapy in RANK-expressing cases, which was statistically significant (P<0.05). In addition, chemotherapy and staging of the tumor were found to independent factors that have an effect on patient survival (P<0.05). Thus, RANK was identified as a negative prognostic factor of osteosarcoma survival.

The Molecular Detection and Clinical Significance of ALK Rearrangement in Selected Advanced Non-Small Cell Lung Cancer: ALK Expression Provides Insights into ALK Targeted Therapy

PubMed Central

Zhang, Ning-Ning; Liu, Yu-Tao; Ma, Li; Wang, Lin; Hao, Xue-Zhi; Yuan, Zheng; Lin, Dong-Mei; Li, Dan; Zhou, Yu-Jie; Lin, Hua; Han, Xiao-Hong; Sun, Yan; Shi, Yuankai

2014-01-01

Background This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients. Methods ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation. Results The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival. Conclusions Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR. PMID:24404167

A Clinicopathological Study of Pemphigus in Eastern India with Special Reference to Direct Immunofluorescence

PubMed Central

Chowdhury, Joyeeta; Datta, Pijush Kanti; Chowdhury, Satyendra Nath; Das, Nilay Kanti

2016-01-01

Background: Pemphigus is a group of chronic autoimmune vesico-bullous disorders in which the epidermis and the basement membrane zone are the focus of attack resulting in cutaneous and mucosal blister formation. Direct immunofluorescence (DIF) test is a very sensitive test for the diagnosis Aim: To study the clinico histopathological patterns of pemphigus in eastern India. The study also aims to correlate DIF with clinical and histologic findings as well as severity of skin involvement [scoring systems]. Materials and Methods: Total 41 patients were studied over a period of 1 year in the Post-graduate centre of Dermatology in Eastern India. DIF, histopathology and clinical data were correlated. Results: In our study Pemphigus vulgaris (PV) was the predominant type with 32 cases followed by 8 cases of pemphigus foliaceus (PF) and a single case of IgA pemphigus. Mean age at presentation was late middle age. Majority of the patients, 26 (63.41%) initially had cutaneous involvement followed by mucosal involvement. In this study group 36 (87.80%) patients showed acantholytic cells on histopathological examination. Most patients of PV showed suprabasal blister 20 (62.50%) followed by intraspinous 5 (15.62%) and subcorneal 5 (15.62%) blister. In majority 28 (87.50%) of the PV patients IgG and C3 antibodies were deposited throughout the epidermis. The strength of antibody positivity was strong in most of the patients (71.87%). In cases of PF mostly IgG 6 (75%) antibodies were deposited in the upper epidermis. DIF intensity had poor correlation with disease activity/severity except in PF. Conclusion: Almost 85.36% cases of pemphigus were diagnosed clinicopathologically. But 6 cases couldn’t be diagnosed accurately on clinicopathological basis and in them DIF was confirmatory. Two cases of pure mucosal PV and 1 case of IgA pemphigus was confirmed by DIF. Two cases of bullous pemphigoid clinico-histologically mimicking PV were also excluded by DIF. So it appears from our study that DIF is confirmatory for diagnosis of pemphigus in all cases. PMID:27293249

Vasculitic wheel - an algorithmic approach to cutaneous vasculitides.

PubMed

Ratzinger, Gudrun; Zelger, Bettina Gudrun; Carlson, J Andrew; Burgdorf, Walter; Zelger, Bernhard

2015-11-01

Previous classifications of vasculitides suffer from several defects. First, classifications may follow different principles including clinicopathologic findings, etiology, pathogenesis, prognosis, or therapeutic options. Second, authors fail to distinguish between vasculitis and coagulopathy. Third, vasculitides are systemic diseases. Organ-specific variations make morphologic findings difficult to compare. Fourth, subtle changes are recognized in the skin, but may be asymptomatic in other organs. Our aim was to use the skin and subcutis as a model and the clinicopathologic correlation as the basic process for classification. We use an algorithmic approach with pattern analysis, which allows for consistent reporting of microscopic findings. We first differentiate between small and medium vessel vasculitis. In the second step, we differentiate the subtypes of small (capillaries versus postcapillary venules) and medium-sized (arterioles/arteries versus veins) vessels. In the final step, we differentiate, according to the predominant cell type, into leukocytoclastic and/or granulomatous vasculitis. Starting from leukocytoclastic vasculitis as a central reaction pattern of cutaneous small/medium vessel vasculitides, its relations or variations may be arranged around it like spokes of a wheel around the hub. This may help establish some basic order in this rather complex realm of cutaneous vasculitides, leading to a better understanding in a complicated field. © 2015 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

An eye witness perspective of the changing patterns of food allergy.

PubMed

Walker-Smith, John

2005-12-01

Food allergy may affect the gastrointestinal tract of children and adults too, albeit less commonly. The changing clinico-pathological expression of such food allergy in children over a 30 year period is related, from the eye witness perspective of a paediatric gastroenterologist in London. Tissue diagnosis by biopsy, related to dietary elimination and challenge has been the basis for the first clinico-pathological descriptions and accurate clinical diagnosis of these syndromes as they affect the gastrointestinal tract. In the 1970s cow's milk sensitive enteropathy presenting as chronic diarrhoea and failure to thrive in infancy often after infective gastroenteritis, especially with enteropathogenic Escherichia coli, was an important problem. By the late 1990s such presentations had become most uncommon in developed communities but they continue to occur in developing communities. By contrast in more recent times, multiple food allergy associated with minor small intestinal enteropathy and gastro-oesophageal reflux in older children has become an important clinical problem in children seen in developed communities. Accompanying these changes has been a dramatic fall in the number of children with clinically severe gastroenteritis with severe dehydration requiring hospital admission. Furthermore, the widespread diagnostic use of endoscopy of the upper and lower gastrointestinal tract in children with multiple biopsies has expanded gastroenterological diagnosis in children. This approach gives information about the oesophagus and ileo-colon not available in the earlier studies, which largely concentrated upon small intestinal biopsies, obtained by Crosby capsule biopsy. So, over this 30 year period clinico-pathological expression has altered but also the diagnostic approach has technically changed.

Genetic Alterations and Their Clinical Implications in High-Recurrence Risk Papillary Thyroid Cancer.

PubMed

Lee, Min-Young; Ku, Bo Mi; Kim, Hae Su; Lee, Ji Yun; Lim, Sung Hee; Sun, Jong-Mu; Lee, Se-Hoon; Park, Keunchil; Oh, Young Lyun; Hong, Mineui; Jeong, Han-Sin; Son, Young-Ik; Baek, Chung-Hwan; Ahn, Myung-Ju

2017-10-01

Papillary thyroid carcinomas (PTCs) frequently involve genetic alterations. The objective of this study was to investigate genetic alterations and further explore the relationships between these genetic alterations and clinicopathological characteristics in a high-recurrence risk (node positive, N1) PTC group. Tumor tissue blocks were obtained from 240 surgically resected patients with histologically confirmed stage III/IV (pT3/4 or N1) PTCs. We screened gene fusions using NanoString's nCounter technology and mutational analysis was performed by direct DNA sequencing. Data describing the clinicopathological characteristics and clinical courses were retrospectively collected. Of the 240 PTC patients, 207 (86.3%) had at least one genetic alteration, including BRAF mutation in 190 patients (79.2%), PIK3CA mutation in 25 patients (10.4%), NTRK1/3 fusion in six patients (2.5%), and RET fusion in 24 patients (10.0%). Concomitant presence of more than two genetic alterations was seen in 36 patients (15%). PTCs harboring BRAF mutation were associated with RET wild-type expression (p=0.001). RET fusion genes have been found to occur with significantly higher frequency in N1b stage patients (p=0.003) or groups of patients aged 45 years or older (p=0.031); however, no significant correlation was found between other genetic alterations. There was no trend toward favorable recurrence-free survival or overall survival among patients lacking genetic alterations. In the selected high-recurrence risk PTC group, most patients had more than one genetic alteration. However, these known alterations could not entirely account for clinicopathological features of high-recurrence risk PTC.

Detection of pAkt protein in imprint cytology of invasive breast cancer: Correlation with HER2/neu, hormone receptors, and other clinicopathological variables.

PubMed

Vasou, Olympia; Skagias, Lazaros; Anastasia, Margariti; Paulina, Athanasiadou; Patsouris, Efstratios; Politi, Ekaterini

2015-01-01

Akt is a serine/threonine protein kinase and has emerged as a crucial regulator of widely divergent cellular processes, including apoptosis, proliferation, differentiation, and metabolism. Activation of Akt/protein kinase B has been positively associated with human epidermal growth-factor receptor 2 (HER2)/neu overexpression in breast carcinoma and a worse outcome among endocrine treated patients. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Archival tumor tissues from 100 patients with invasive breast carcinoma were analyzed by immunocytochemistry. This study describes the results of immunocytochemical pAkt expression in breast carcinoma imprints, prepared from cut surfaces of freshly removed tumors. Both nuclear and cytoplasmic expressions were evaluated for pAkt. Nuclear and cytoplasmic positive scores of 72% (72/100) and 42% (42/100), respectively, were found. Coexistence of nuclear and cytoplasmic staining was observed in 32 cases (32/100). Nuclear positive staining correlated with HER2/neu overexpression (P = 0.043) and was significantly associated with positive involvement of axillary lymph nodes (P = 0.013). No correlation was found between cytoplasmic pAkt rate and clinicopathological parameters, estrogen receptor, progesterone receptor or HER2/neu expression. pAkt expression can be evaluated in cytological material and may add valuable information to current prognostic models for breast cancer. pAkt overexpression appears to be linked with potentially aggressive tumor phenotype in invasive breast carcinoma.

The Implications of Endoscopic Ulcer in Early Gastric Cancer: Can We Predict Clinical Behaviors from Endoscopy?

PubMed Central

Lee, Yoo Jin; Kim, Jie-Hyun; Park, Jae Jun; Youn, Young Hoon; Park, Hyojin; Kim, Jong Won; Choi, Seung Ho; Noh, Sung Hoon

2016-01-01

Background The presence of ulcer in early gastric cancer (EGC) is important for the feasibility of endoscopic resection, only a few studies have examined the clinicopathological implications of endoscopic ulcer in EGC. Objectives To determine the role of endoscopic ulcer as a predictor of clinical behaviors in EGC. Methods Data of 3,270 patients with EGC who underwent surgery between January 2005 and December 2012 were reviewed. Clinicopathological characteristics were analyzed in relation to the presence and stage of ulcer in EGC. Based on endoscopic findings, the stage of ulcer was categorized as active, healing, or scar. Logistic regression analysis was performed to analyze factors associated with lymph node metastasis (LNM). Results 2,343 (71.7%) patients had endoscopic findings of ulceration in EGC. Submucosal (SM) invasion, LNM, lymphovascular invasion (LVI), perineural invasion, and undifferentiated-type histology were significantly higher in ulcerative than non-ulcerative EGC. Comparison across different stages of ulcer revealed that SM invasion, LNM, and LVI were significantly associated with the active stage, and that these features exhibited significant stage-based differences, being most common at the active stage, and least common at the scar stage. The presence of endoscopic ulcer and active status of the ulcer were identified as independent risk factors for LNM. Conclusions Ulcerative EGC detected by endoscopy exhibited more aggressive behaviors than non-ulcerative EGC. Additionally, the endoscopic stage of ulcer may predict the clinicopathological behaviors of EGC. Therefore, the appearance of ulcers should be carefully evaluated to determine an adequate treatment strategy for EGC. PMID:27741275

GTF2I mutation frequently occurs in more indolent thymic epithelial tumors and predicts better prognosis.

PubMed

Feng, Yanfen; Lei, Yiyan; Wu, Xiaoyan; Huang, Yuhua; Rao, Huilan; Zhang, Yu; Wang, Fang

2017-08-01

A missense mutation in GTF2I was previously identified in thymic epithelioid tumor (TET). However, the clinicopathological relevance of GTF2I mutation has not been illustrated. We studied the prognostic importance of GTF2I mutation as well as its relation to histological subtypes in a large number of TETs. TET samples from 296 patients with clinical and follow-up data were collected, and histological subtypes were classified. Analysis of the GTF2I (chromosome 7 c.74146970T>A) mutation was undertaken by using quantitative real time polymerase chain reaction (qPCR) and direct sequencing. The association of GTF2I mutation with clinicopathological features as well as prognosis was analyzed. One hundred twenty-four out of 296 (41.9%) patients harbored the GTF2I mutation (chromosome 7 c.74146970T>A). GTF2I mutation was observed in 20 (87.0%) cases of type A thymoma, 70 (78.7%) of type AB thymoma, and the frequency decreased with the degree of histological subtype aggressiveness, with the lowest rate in thymic carcinoma (7.7%). The difference of GTF2I mutation distribution in histological subtypes was statistically significant (p<0.001). The GTF2I mutation was found more frequently in patients with early Masaoka stage (I-II, n=112, 90.3%) than in those with advanced stage (III-IV) disease (n=12, 9.6%, p<0.001). However, only histological subtype significantly predicted the presence of the GTF2I mutation in patients with TETs. The presence of the GTF2I mutation correlated with better prognosis (90.0% compared to 72.0% 5-year survival, and 86% compared to 56% 10-year survival, respectively; log-rank p=0.001). Moreover, it was an independent prognostic factor [hazard ratio (HR), 0.35; 95% confidential interval (CI), 0.15-0.81; p=0.014)]. The frequency of the GTF2I mutation is higher in more indolent TETs, and correlates with better prognosis. Further studies are required to elucidate the role of the GTF2I mutation in TETs and its clinical application. Copyright © 2017 Elsevier B.V. All rights reserved.

Oncogene GAEC1 regulates CAPN10 expression which predicts survival in esophageal squamous cell carcinoma

PubMed Central

Chan, Dessy; Tsoi, Miriam Yuen-Tung; Liu, Christina Di; Chan, Sau-Hing; Law, Simon Ying-Kit; Chan, Kwok-Wah; Chan, Yuen-Piu; Gopalan, Vinod; Lam, Alfred King-Yin; Tang, Johnny Cheuk-On

2013-01-01

AIM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was studied by using the RNA interference (RNAi) approach through transfecting the GAEC1-overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1-targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1-targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10) and upregulation of trinucleotide repeat containing 6C (TNRC6C) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 ± 16.33 vs 12.62 ± 12.44, P = 0.032). No significant correction was observed among the TNRC6C protein expression level and the clinocopathologcial features of esophageal squamous cell carcinoma. CONCLUSION: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma. PMID:23687414

Comparison of the Operative Outcomes and Learning Curves between Laparoscopic and Robotic Gastrectomy for Gastric Cancer

PubMed Central

Huang, Kuo-Hung; Lan, Yuan-Tzu; Fang, Wen-Liang; Chen, Jen-Hao; Lo, Su-Shun; Li, Anna Fen-Yau; Chiou, Shih-Hwa; Wu, Chew-Wun; Shyr, Yi-Ming

2014-01-01

Background Minimally invasive surgery, including laparoscopic and robotic gastrectomy, has become more popular in the treatment of gastric cancer. However, few studies have compared the learning curves between laparoscopic and robotic gastrectomy for gastric cancer. Methods Data were prospectively collected between July 2008 and Aug 2014. A total of 145 patients underwent minimally invasive gastrectomy for gastric cancer by a single surgeon, including 73 laparoscopic and 72 robotic gastrectomies. The clinicopathologic characteristics, operative outcomes and learning curves were compared between the two groups. Results Compared with the laparoscopic group, the robotic group was associated with less blood loss and longer operative time. After the surgeon learning curves were overcome for each technique, the operative outcomes became similar between the two groups except longer operative time in the robotic group. After accumulating more cases of robotic gastrectomy, the operative time in the laparoscopic group decreased dramatically. Conclusions After overcoming the learning curves, the operative outcomes became similar between laparoscopic and robotic gastrectomy. The experience of robotic gastrectomy could affect the learning process of laparoscopic gastrectomy. PMID:25360767

Clinicopathological and Molecular Factors, Risk Factors, Treatment Outcomes and Risk of Recurrence in Mesenteric and Retroperitoneal Extragastrointestinal Stromal Tumors.

PubMed

Apostolou, Konstantinos G; Schizas, Dimitrios; Vavouraki, Eleni; Michalinos, Adamantios; Tsilimigras, Diamantis I; Garmpis, Nikolaos; Damaskos, Christos; Papalampros, Alexandros; Liakakos, Theodore

2018-04-01

The objective of the present study was to determine the clinicopathological factors and treatment outcomes of patients suffering from mesenteric or retroperitoneal extragastrointestinal stromal tumors (EGISTs). A detailed search in PubMed, using the key words "extragastrointestinal stromal tumors" and "EGIST", found eight studies fulfilling the criteria of this study. Thirty-six patients with a mesenteric and 24 patients with a retroperitoneal EGIST were analyzed, with a follow-up period ranging from 2 to 192 months. Retroperitoneal tumors presented as larger tumors than mesenteric ones, with 95% and 93% immunohistochemical positivity for CD117 antigen, respectively. Surgical resection was performed in 91% of cases, with 57% of patients with mesenteric and 70% of patients with retroperitoneal EGISTs being alive at the last follow-up. EGISTs most commonly are of considerable size and usually with a high mitotic count, rendering them high-risk tumors. Tumor necrosis, nuclear atypia, tumor histology, and mutations in the tyrosine kinase KIT or platelet-derived growth factor receptor A (PDGFRA) gene, seem to influence tumor behavior. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Impacts of ICAM-1 gene polymorphisms on urothelial cell carcinoma susceptibility and clinicopathologic characteristics in Taiwan.

PubMed

Wang, Shian-Shiang; Hsieh, Ming-Ju; Ou, Yen-Chuan; Chen, Chuan-Shu; Li, Jian-Ri; Hsiao, Pei-Ching; Yang, Shun-Fa

2014-08-01

Intercellular adhesion molecule (ICAM)-1, a cell adhesion molecule, is reportedly overexpressed in several cancers and may contribute to tumorgenesis and metastasis. The current study explored the effect of ICAM-1 gene polymorphisms on the susceptibility of developing urothelial cell carcinoma (UCC) and the clinicopathological status. A total of 558 participants, including 279 healthy people and 279 patients with UCC, were recruited for this study. Four single-nucleotide polymorphisms of the ICAM-1 gene were assessed by a real-time polymerase chain reaction with the TaqMan assay. After adjusting for other covariants, the individuals carrying at least one G allele at ICAM-1 rs5498 had a 1.603-fold risk of developing UCC than did wild-type (AA) carriers. Furthermore, UCC patients who carried at least one G allele at rs5498 had a higher invasive stage risk (p < 0.05) than did patients carrying the wild-type allele. In conclusion, the rs5498 polymorphic genotypes of ICAM-1 might contribute to the prediction of susceptibility to and pathological development of UCC. This is the first study to provide insight into risk factors associated with ICAM-1 variants in carcinogenesis of UCC in Taiwan.

Merkel cell carcinoma of the head and neck: poorer prognosis than non-head and neck sites.

PubMed

Morand, G B; Madana, J; Da Silva, S D; Hier, M P; Mlynarek, A M; Black, M J

2016-04-01

Merkel cell carcinoma is a rare, aggressive neurocutaneous malignancy. This study investigated whether patients with Merkel cell carcinoma in the head and neck had poorer outcomes than patients with Merkel cell carcinoma located elsewhere. A retrospective study was performed of patients with Merkel cell carcinoma treated at the Jewish General Hospital in Montréal, Canada, from 1993 to 2013. Associations between clinicopathological characteristics and disease-free and disease-specific survival rates were examined according to the Kaplan-Meier method. Twenty-seven patients were identified. Although basic clinicopathological characteristics and treatments were similar between head and neck and non-head and neck Merkel cell carcinoma groups, disease-free and disease-specific survival rates were significantly lower in the head and neck Merkel cell carcinoma group (log-rank test; p = 0.043 and p = 0.001, respectively). Mortality was mainly due to distant metastasis. Patients with head and neck Merkel cell carcinoma had poorer survival rates than patients with non-head and neck Merkel cell carcinoma in our study. The tendency to obtain close margins, a less predictable metastatic pattern, and/or intrinsic tumour factors related to the head and neck may explain this discrepancy.

A comparison of oncological outcomes between transoral surgical and non-surgical treatment protocols in the management of oropharyngeal squamous cell carcinoma.

PubMed

Kao, S S; Micklem, J; Ofo, E; Edwards, S; Dhatrak, D; Foreman, A; Krishnan, S; Hodge, J-C

2018-04-01

The incidence of oropharyngeal squamous cell carcinoma in the Western world is increasing, with the human papillomavirus epidemic implicated in this observed trend. The optimal treatment modality is yet undetermined regarding oncological outcomes. This study comprised 98 patients with oropharyngeal squamous cell carcinoma, treated with either primary transoral surgery with adjuvant therapy or primary chemoradiotherapy with curative intent, between 2008 and 2012. Clinicopathological characteristics including tumour-node-metastasis stage, human papillomavirus status, treatment modality, recurrence and overall survival were collated. Five per cent of primary surgical patients had locoregional recurrences compared with 25 per cent of primary chemoradiotherapy patients. A lower rate of locoregional recurrence was observed in the human papillomavirus positive group. This paper reports higher rates of overall survival and local control for oropharyngeal squamous cell carcinoma treated with primary surgery compared with primary chemoradiotherapy. This reflects overall lower tumour stage and higher human papillomavirus status in this group.

Expression of Glut-1 is a prognostic marker for oral squamous cell carcinoma patients.

PubMed

Eckert, A W; Lautner, M H W; Taubert, H; Schubert, J; Bilkenroth, U

2008-12-01

Oral squamous cell carcinoma (OSCC) is among the tenth most common human cancers worldwide with evidence of an increase in incidence rate and mortality. Despite advances in treatment modalities, the prognosis of this cancer is still very poor and has not changed over the past two decades. This study is based on samples collected from 42 patients with a primary OSCC. Immunohistochemical staining for Glut-1 was carried out and compared with the clinicopathological data. Thirty-two patients showed in their tumors a weak or undetectable Glut-1 expression, whereas in tumors of 10 patients a moderate to strong Glut-1 expression was detected. In multivariate Cox's regression hazard analysis, patients whose tumors had a moderate to strong Glut-1 expression possessed a 4.9-fold increased risk of tumor-related death compared to the other patients. Our results suggest that Glut-1 expression is an independent prognostic marker for routine assessment of OSCC.

Comparative clinicopathological and cytomorphological analyses of peritoneal carcinomatosis associated with metastatic breast carcinoma and primary peritoneal/ovarian carcinoma in patients with a history of breast carcinoma.

PubMed

Na, Kiyong; Lee, Jung-Yun; Sung, Ji-Youn; Kim, Gun Min; Koo, Ja Seung; Kim, Hyun-Soo

2018-06-20

Causes of peritoneal carcinomatosis (PC) in patients with a history of breast carcinoma include both metastatic breast carcinoma (MBC) and primary peritoneal/ovarian carcinoma (PPOC). The origin of PC is important to determine the appropriate treatment strategy. Cytological examination of the peritoneal fluid (PF), which may be the first diagnostic approach to PC, is of distinct value in confirming the presence of malignant cells and determining the origin of PC. We analyzed the clinicopathological and cytomorphological characteristics of 33 patients with a history of breast carcinoma whose PF cytology contained malignant cells. Cases showing positive immunoreactivity for PAX8 and a lack of GATA3 expression were considered as PPOC. Sixteen patients developed PC caused by PPOC. PPOC patients were characterized by early-stage primary breast carcinoma, absence of non-peritoneal MBC before PC, and normal serum levels of CEA and CA15-3. Fourteen PPOC patients had pathogenic germline BRCA mutations. Cytological examination revealed that most of the PPOC cases had a dominant papillary arrangement of the tumor cells with severe nuclear pleomorphism, occasional bizarre nuclei, and atypical mitotic figures. Patients with PPOC who underwent cytoreductive surgery had a significantly longer survival time compared to those who did not, or MBC patients. In patients with a history of breast carcinoma presenting with PC, the presence of early-stage primary breast carcinoma, no prior non-peritoneal MBC, and a dominant papillary cellular arrangement pattern in the PF cytology were independent predictors of PPOC. Cytoreductive surgery significantly improved survival for patients with PPOC.

Massive Gastric Juvenile Polyposis: A Clinicopathologic Study Using SMAD4 Immunohistochemistry.

PubMed

Lawless, Margaret E; Toweill, Daniel L; Jewell, Kim D; Jain, Dhanpat; Lamps, Laura; Krasinskas, Alyssa M; Swanson, Paul E; Upton, Melissa P; Yeh, Matthew M

2017-04-01

Juvenile polyps involving the stomach are uncommon. Massive gastric juvenile polyposis is even rarer. We describe the clinicopathologic features of nine cases of massive gastric juvenile polyposis. All patients had anemia; four had hypoalbuminemia. The polyps were composed predominantly of dilated crypts lined by columnar epithelium and abundant edematous stroma with mixed inflammatory infiltrates. One patient had a poorly differentiated adenocarcinoma, arising in juvenile polyp-associated intraepithelial neoplasia. A second patient had a well-differentiated intramucosal adenocarcinoma arising in a juvenile polyp with high-grade dysplasia. Three of our cases had polyposis restricted to the stomach. Six (66.6%) had loss of SMAD4 immunoreactivity, making them subject to severe bleeding and hypoproteinemia, as well as developing severe dysplasia or adenocarcinoma. SMAD4 immunohistochemstry is a helpful ancillary diagnostic test in cases of suspected juvenile polyposis syndrome involving the stomach. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Clinicopathologic correlation of submacular membranectomy with retention of good vision in a patient with age-related macular degeneration.

PubMed

Rosa, R H; Thomas, M A; Green, W R

1996-04-01

We present the clinicopathologic features of the eye of a patient with age-related macular degeneration who underwent submacular membranectomy and had retention of good visual acuity for almost 4 years despite recurrent choroidal neovascularization treated with krypton laser photocoagulation and mild expansion of the laser lesion with time. Histopathologic study of the surgically removed membrane from the right eye disclosed a thin fibrovascular membrane lined by retinal pigment epithelium on one surface. Microscopic examination of the right eye obtained post mortem disclosed a 2.75-mm (horizontal) x 2.1-mm (vertical) retinal pigment epithelium defect with overlying photoreceptor cell atrophy centered on the temporal parafoveal area, and a 0.6 x 0.1-mm subretinal pigment epithelium fibrovascular membrane with an area of retinal pigment epithelial hyperplasia and vascularization from the retina 0.4 mm temporal to the fovea. Basal laminar deposit was present in the region of the fovea and nasal parafoveal area.

Immunotactoid Glomerulopathy and Cryoglobulinemic Nephropathy: Two Entities with Many Similarities. A Unified Conceptual Approach.

PubMed

Herrera, Guillermo A; Ojemakinde, Kunle O; Turbat-Herrera, Elba A; Gu, Xin; Zeng, Xu; Iskandar, Samy S

2015-01-01

Immunotactoid glomerulopathy is a rare disorder that has been characterized at the ultrastructural level. Due to its rarity, there are few comprehensive studies relating to this disorder. Electron microscopy essentially characterizes this disease. The glomerular electron dense deposits which are typical of this condition consist of aggregates of highly organized microtubular structures of various diameters, but generally measuring 30-50 nm in width with a propensity to dispose themselves in parallel bundles intersecting in different planes. This study compares a large series of patients with cryoglobulinemic nephropathy with a series of patients with immunotactoid glomerulopathy to address whether there may be similarities that warrant considering these two entities part of a spectrum. This study reviews the clinicopathologic features of both entities and emphasizes ultrastructural findings that characterize them. Significant immunomorphologic overlap was found when these two disorders were compared in this study. There were also striking similarities in clinical presentation/behavior, laboratory findings and prognosis. Proteomic analysis has also demonstrated similar spectra for both entities. We postulate that immunotactoid glomerulopathy and cryoglobulinemic nephropathy are part of the spectrum of renal manifestations in patients with circulating cryoglobulins and renal disease.

A cross-sectional study of elderly Asian and European women with primary operable breast cancer aged 70 and older. Are there differences?

PubMed

Tea, Muy-Kheng M; Tang, Lichen; Di, Gen-Hong; Muin, Dana; Steurer, Stefan; Delancey, James W; Shao, Zhi-Ming; Singer, Christian F

2012-11-01

Breast cancer (BC) is becoming a disease of the elderly. Additionally, BC-incidence is rising in Asia. The aim of this study was to explore clinico-pathological characteristics and differences of breast cancer in elderly Asian/Han-Chinese compared to Caucasian/Austrian women. A total number of 630 consecutive primary operable, unilateral breast cancer cases, 70 years and older, were analyzed. Histo-pathological findings and biological characteristics of 198 Caucasian/Austrian were compared with 432 Asian/Han-Chinese. Pearson's chi-square test was used to assess differences in the analyzed populations. A significantly higher rate of triple-negative BC (p=0.027) was diagnosed among the Chinese geriatric population. More estrogen-receptor positive BC was detected in the Caucasian study group (p<0.001). No statistically significant differences were detected based on tumor size, axillary lymph-node status, nor HER2-receptor expression. This study will help us gain additional ethnic-specific insight into the biological characteristics of breast cancer in the elderly Caucasian/Austrian and Asian/Han-Chinese populations. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Comparison of clinicopathologic characteristics of urothelial carcinoma between patients after renal transplantation and on dialysis.

PubMed

Zhang, Bo; Shen, Cheng; Han, Wen-ke; Yu, Wei

2014-09-15

Urothelial carcinoma (UC) is a common complication after renal replacement therapy (RRT) among Chinese end-stage renal disease (ESRD) patients. It is unclear whether there are any differences in the clinicopathologic characteristics of UC between renal transplantation (RT) and dialysis patients; such differences could impact RRT modality selection. We retrospectively reviewed clinicopathologic data for 27 RT patients and 40 dialysis patients who were diagnosed with UC in our center to explore differences in the clinicopathologic characteristics of UC and prognoses between the two groups. The median follow-up period was 92 months (2-137) for the RT group and 71 months (18-155) for the dialysis group. The demographic and baseline data showed no significant differences between the two groups. Upper urinary tract UC (UUC) occurred more frequently in the RT group (22 UUCs in 39 UCs), whereas bladder UC (BUC) predominated in the dialysis group (33 BUCs in 49 UCs) (P=0.025). The pathologic grading in the RT group was significantly higher than that in the dialysis group (P=0.046 for WHO1973 grading, P=0.026 for WHO2004 grading), whereas the difference in tumor stage was not significant (P=0.089). The RT group manifested a higher recurrence rate than the dialysis group (P=0.024). However, the overall and cancer-specific survival rates between the two groups were not significantly different (P=0.239 and P=0.818, respectively). Certain traits of UC, including tumor site, pathologic grading, and recurrence-free survival, were notably different between RT and dialysis patients, but the overall and cancer-specific survival rates were similar.

DNA methylation-induced E-cadherin silencing is correlated with the clinicopathological features of melanoma.

PubMed

Venza, Mario; Visalli, Maria; Catalano, Teresa; Biondo, Carmelo; Beninati, Concetta; Teti, Diana; Venza, Isabella

2016-04-01

E-cadherin, a calcium-dependent cell-cell adhesion molecule, has an important role in epithelial cell function, maintenance of tissue architecture and cancer suppression. Loss of E-cadherin promotes tumor metastatic dissemination and predicts poor prognosis. The present study investigated the clinicopathological significance of E-cadherin expression in cutaneous, mucosal and uveal melanoma related to epigenetic mechanisms that may contribute to E-cadherin silencing. E-cadherin expression was reduced in 55/130 cutaneous (42.3%), 49/82 mucosal (59.7%) and 36/64 uveal (56.2%) melanoma samples as compared to normal skin controls and was inversely associated with promoter methylation. Of the 10 different CpG sites studied (nt 863, 865, 873, 879, 887, 892, 901, 918, 920 and 940), two sites (nt 892 and 940) were 90-100% methylated in all the melanoma specimens examined and the other ones were partially methylated (range, 53-86%). In contrast, the methylation rate of the E-cadherin gene was low in normal tissues (range, 5-24%). In all the three types of melanoma studied, a significant correlation was found between reduced levels of E-cadherin and reduced survival, high mitotic index and metastasis, accounting for the predilection of lymph nodal localization. In cutaneous and mucosal melanoma, low E-cadherin expression was positively correlated also with head/neck localization and ulceration. A high frequency of reduced E-cadherin levels occurred in choroid melanomas. In vitro experiments showed that E-cadherin transcription was restored following 5-aza-2'-deoxycytidine (5-aza-dC) treatment or DNMT1 silencing and was negatively correlated with the invasive potential of melanoma cells. The significant relationship between E-cadherin silencing and several poor prognostic factors indicates that this adhesion molecule may play an important role in melanomagenesis. Therefore, the inverse association of E-cadherin expression with promoter methylation raises the intriguing possibility that reactivation of E-cadherin expression through promoter demethylation may represent a potential therapeutic strategy for the treatment of melanoma.

Clinicopathologic study of succinate-dehydrogenase-deficient gastrointestinal stromal tumors: A single-institutional experience in China.

PubMed

Liu, Weizhen; Zeng, Xiangyu; Wu, Xiuli; He, Jun; Gao, Jinbo; Shuai, Xiaoming; Wang, Guobin; Zhang, Peng; Tao, Kaixiong

2017-08-01

Gastrointestinal stromal tumors (GISTs) that are not driven by kinase mutations, as are most GISTs, often show loss of function of the succinate dehydrogenase (SDH) complex and are considered SDH-deficient GISTs. SDH-deficient GISTs share many distinct characteristics compared with conventional GISTs. However, data regarding these characteristics, particularly among Asian people, are relatively limited. The objective of this study was to characterize the clinicopathologic characteristics, treatment, and prognosis of these uncommon GISTs.This retrospective observational study enrolled 12 patients with SDH-deficient GISTs, who were selected from 335 patients with GIST diagnosed at our institution between October 31, 2013 and October 31, 2016 by succinate dehydrogenase subunit B staining.There were 8 male and 4 female patients, with a median age of 57 years (range, 21-73 years). Ten patients (83.3%) were diagnosed at or after the age of 40 years and represented 7.2% (10/138) of the entire population of elderly patients with gastric GISTs. The tumor size ranged from 3 to 19 cm (median, 7 cm); the primary tumor was multifocal in 6 cases (50%), and tumors had a multinodular or plexiform architecture in 10 cases (83.3%). Ten cases (83.3%) showed pure epithelioid morphology, with the remaining 2 cases (16.7%) showing mixed histologic subtype. Lymph node metastasis was found at the time of primary resection in 50% (3/6) of patients. Four cases (33.3%) had distant metastasis at presentation. Four patients (33.3%) developed disease progression during imatinib treatment after initial resection, but all of these patients regained disease control when the treatment was altered to sunitinib targeted therapy.SDH-deficient GISTs arise exclusively in the stomach and account for approximately 7.4% (12/162) of gastric GISTs. Moreover, those affecting people older than 40 years are not uncommon and sunitinib may work well for cases showing treatment failure with imatinib.

Primary central nervous system lymphoma in immunocompetent individuals: a single center experience.

PubMed

Aki, Hilal; Uzunaslan, Didem; Saygin, Caner; Batur, Sebnem; Tuzuner, Nukhet; Kafadar, Ali; Ongoren, Seniz; Oz, Buge

2013-01-01

Primary central nervous system lymphoma (PCNSL) is defined as the involvement of brain, leptomeninges, eyes or spinal cord by non-Hodgkin lymphoma. The role of various prognostic markers in predicting adverse outcome is debated. To investigate the clinical and immunohistochemical findings of immunocompetent PCNSL cases (39 cases) diagnosed at the study center, and evaluate the influence of potential prognostic factors on overall survival (OS) of patients. Data regarding patient characteristics, neuroimaging, pathological and immunohistochemical features and follow-up were obtained from patient records. The influence of potential prognostic parameters on OS was investigated by log-rank test and Cox regression analysis. Patients who received combined chemotherapy and radiotherapy had a significantly better OS when compared to chemotherapy alone. Other variables included in this study were not associated with a significant survival advantage. In this study, we failed to demonstrate a relationship between different clinicopathological variables and OS of patients. Prospective studies with large patient series are needed to investigate other potential prognostic factors.

Expression of interleukine-8 as an independent prognostic factor for sporadic colon cancer dissemination

PubMed Central

Nastase, A; Paslaru, L; Herlea, V; Ionescu, M; Tomescu, D; Bacalbasa, N; Dima, S; Popescu, I

2014-01-01

Abstract Aim: The aim of our study was to investigate the gene and serum protein expression profiles of IL-8 in colon cancer and associated hepatic metastasis and to correlate these results with clinicopathologic variables of the patients. Materials and methods: IL-8 was evaluated by qPCR and ELISA in a total number of 62 colon cancer patients (n=42 by qPCR and n=20 by ELISA) in normal and tumoral tissue specimens and serum samples respectively. Additionally synchronous metastasis from 5 of these patients were also collected at the time of surgery and analyzed by qPCR. Results: IL-8 was up regulated in all analyzed tumoral samples compared with normal tissue (P-value = 0.01) and higher expressed in metastatic tissues compared with tumoral tissues (P -value= 0.03). The median expression of IL-8 in patients over 60 years old was found to be higher compared with the median expression of IL8 in patients less than 60 years old (3.89 compared with 14.69, P -value= 0.005). According to tumor grading, we found that IL-8 in tumors with well differentiated adenocarcinoma have a median mRNA expression of 9.78 compared with a median mRNA IL8 expression of 26.63 in moderate or poor differentiated adenocarcinoma. Levels of IL-8 determined in serum were statistically significant correlated with preoperative carcinoembryonic antigen level (P -value= 0.003, R=0.57) and with distant metastasis (P-value =0.008). Serum level of IL-8 increased proportionally along with TNM tumor stage and was found to be statistically significant correlated with C-reactive protein (P -value, R=0.64). Colon cancer patients had higher IL-8 levels as determined by ELISA (median value= 29.64 pg/ml) compared with healthy controls (median value= 4.86 pg/ml). Discussions: Our results provide additional support for the role of inflammation in colon cancer and indicate that IL-8 could be further validated in association with other already used markers for prognostic and diagnostic of evolutional disease in colon cancer patients. Brief abstract By investigating the gene and serum protein expression profiles of IL-8 in colon cancer and associated hepatic metastasis, we found correlations between these results and clinicopathological variables of the patients. IL-8 is involved in colon cancer progression and could be monitored in a panel with other biomarkers as an early indicator of the tumor’s evolution. PMID:25408728

[Analysis of the Role of PET/CT SUVmax in Prognosis and Its Correlation with 
Clinicopathological Characteristics in Resectable Lung Squamous Cell Carcinoma].

PubMed

Ren, Hongliang; Xu, Wengui; You, Jian; Song, Xiuyu; Huang, Hui; Zhao, Ning; Ren, Xiubao; Zhang, Xinwei

2016-04-20

Lung cancer is the leading cause of cancer death in men and women in the world, more than one-half of cases are diagnosed at a advanced stage, and the overall 5-year survival rate for lung cancer is 18%. Lung cancer is divided into non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC). Approximately 80%-85% of cases are NSCLC which includes three main types: adenocarcinoma (40%), squamous cell carcinoma (SCC) (20%-30%), and large cell carcinoma (10%). Although therapies that target driver mutations in adenocarcinomas are showing some promise, they are proving ineffective in smoking-related SCC. We need pay more attention to the diagnosis and treatment of SCC. 18F-FDG positron emission tomography (PET)/computed tomography (CT) has emerged as an accurate staging modality in lung cancer diagnosis. The aim of this study is to investigate the role of maximum standardized uptake value (SUVmax) on PET-CT in prognosis and its correlation with clinicopathological characteristics in resectable SCC. One hundred and eighty-two resectable SCC patients who underwent PET/CT imaging between May 2005 and October 2014 were enrolled into this retrospectively study. All the enrolled patients had underwent pulmonary resection with mediastinal lymph node dissection without preoperative chemotherapy or radiotherapy. Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model. Correlation between SUVmax and clinicopathological factors was analysed using Pearson correlation analysis and Spearman rank correlation analysis. The patients were divided into two groups on the basis of SUVmax 13.0 as cutoff value, and patients with SUVmax more than 13.0 had shorter median overall survival than patients less than 13.0 in univariate analysis (56 months vs 87 months; P=0.022). There was remarkable correlation between SUVmax and gender, tumor size, tumor-node-metastasis (TNM) stage, neutrophil, NLR, hemoglobin (P<0.05). Multivariate Cox analysis demonstrated that SUVmax (HR=1.714, 95%CI: 1.021-2.876, P=0.042), TNM stage (HR=1.677, 95%CI: 1.231-2.284, P=0.001) were independent predictors for survival. Furthermore, univariate survival analysis showed significant difference by SUVmax in patients of stage I (P=0.045). SUVmax may be of importance prognostic factor independent of TNM stage, which was considerable for risk stratification in patients with TNM stage. Besides, there was correlation between SUVmax of primary tumor and clinicopathological characteristics.
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[Nonspecific interstitial pneumonitis: a clinicopathologic entity, histologic pattern or unclassified group of heterogeneous interstitial pneumonitis?].

PubMed

Morais, António; Moura, M Conceição Souto; Cruz, M Rosa; Gomes, Isabel

2004-01-01

Nonspecific interstitial pneumonitis (NSIP) initially described by Katzenstein and Fiorelli in 1994, seems to be a distinct clinicopathologic entity among idiopathic interstitial pneumonitis (IIP). Besides different histologic features from other IIP, NSIP is characterized by a better long-term outcome, associated with a better steroids responsiveness than idiopathic pulmonar fibrosis (IPF), where usually were included. Thus, differentiating NSIP from other IIP, namely IPF is very significant, since it has important therapeutic and prognostic implications. NSIP encloses different pathologies, namely those with inflammatory predominance (cellular subtype) or fibrous predominance (fibrosing subtype). NSIP is reviewed and discussed by the authors, after two clinical cases description.

A Clinicopathological Analysis of Soft Tissue Sarcoma with Telangiectatic Changes.

PubMed

Kobayashi, Hiroshi; Ae, Keisuke; Tanizawa, Taisuke; Gokita, Tabu; Motoi, Noriko; Matsumoto, Seiichi

2015-01-01

Background. Soft tissue sarcoma with a hemorrhagic component that cannot be easily diagnosed by needle biopsy is defined here as soft tissue sarcoma with telangiectatic changes (STST). Methods. We retrospectively reviewed clinicopathological data of STST from 14 out of 784 patients (prevalence: 1.8%) with soft tissue sarcoma. Results. Tumors were found mostly in the lower leg. Histological diagnoses were undifferentiated pleomorphic sarcoma (n = 5), synovial sarcoma (n = 5), epithelioid sarcoma (n = 2), and malignant peripheral nerve sheath tumor and fibrosarcoma (n = 1). No history of trauma to the tumor site was recorded in any patient. Needle aspiration transiently reduced the tumor volume, but subsequent recovery of tumor size was observed in all cases. Out of 14 patients, 9 presented with a painful mass. MRI characteristics included intratumoral nodules (64.3%). The local recurrence rate was 14.3%, and the 2-year event-free survival rate was poorer (50%) than that of most sarcomas. Conclusions. STST is unique in its clinicopathological presentation. Painful hematomas without a trauma history, intratumoral nodules within a large hemorrhagic component, and subsequent recovery of tumor size after aspiration are indicative of the presence of STST.

A Clinicopathological Analysis of Soft Tissue Sarcoma with Telangiectatic Changes

PubMed Central

Kobayashi, Hiroshi; Ae, Keisuke; Tanizawa, Taisuke; Gokita, Tabu; Motoi, Noriko; Matsumoto, Seiichi

2015-01-01

Background. Soft tissue sarcoma with a hemorrhagic component that cannot be easily diagnosed by needle biopsy is defined here as soft tissue sarcoma with telangiectatic changes (STST). Methods. We retrospectively reviewed clinicopathological data of STST from 14 out of 784 patients (prevalence: 1.8%) with soft tissue sarcoma. Results. Tumors were found mostly in the lower leg. Histological diagnoses were undifferentiated pleomorphic sarcoma (n = 5), synovial sarcoma (n = 5), epithelioid sarcoma (n = 2), and malignant peripheral nerve sheath tumor and fibrosarcoma (n = 1). No history of trauma to the tumor site was recorded in any patient. Needle aspiration transiently reduced the tumor volume, but subsequent recovery of tumor size was observed in all cases. Out of 14 patients, 9 presented with a painful mass. MRI characteristics included intratumoral nodules (64.3%). The local recurrence rate was 14.3%, and the 2-year event-free survival rate was poorer (50%) than that of most sarcomas. Conclusions. STST is unique in its clinicopathological presentation. Painful hematomas without a trauma history, intratumoral nodules within a large hemorrhagic component, and subsequent recovery of tumor size after aspiration are indicative of the presence of STST. PMID:26839509

Lgr5High/DCLK1High phenotype is more common in early stage and intestinal subtypes of gastric carcinomas.

PubMed

Kalantari, Elham; Asadi Lari, Mohammad Hossein; Roudi, Raheleh; Korourian, Alireza; Madjd, Zahra

2017-12-06

Gastric carcinoma is the third most common malignancy and is one of the main causes of cancer deaths worldwide. Cancer stem cells (CSCs) are a subpopulation of tumour cells capable of self-renewal and differentiation, likely responsible for the initiation, recurrence, metastasis and chemo/radio-resistance. This study was conducted to evaluate the expression patterns and clinicopathologic significance of putative CSC markers, Lgr5 and DCLK1, in gastric carcinoma. The expression levels of Lgr5 and DCLK1 were examined in a well-defined series of gastric carcinoma tissues, including 75 (80%) from intestinal and 19 (20%) from diffuse subtypes, using tissue microarray (TMA). In addition, the correlation of the expression of these markers with clinicopathological factors was explored. Higher expressions of Lgr5 and DCLK1 were mainly detected in intestinal subtypes of gastric carcinomas compared to diffuse subtypes (P= 0.005 and P= 0.050, respectively). We also found a higher expression of Lgr5 and DCLK1 more frequently in well-differentiated gastric carcinoma cases (P< 0.001 and P= 0.007). The combined analysis demonstrated that the co-expression of Lgr5 and DCLK1 (Lgr5High/DCLK1High) was more common in intestinal subtypes (P= 0.025) and well-differentiated gastric carcinoma samples (P< 0.001). Interestingly, there was a significant correlation between Lgr5High/DCLK1High phenotype and early-stage gastric carcinoma specimens (P= 0.045). Our findings indicated that the Lgr5High/DCLK1High expression pattern may be considered as a signature phenotype for intestinal subtypes of gastric carcinoma.

The ESR1 and GPX1 gene expression level in human malignant and non-malignant breast tissues.

PubMed

Król, Magdalena B; Galicki, Michał; Grešner, Peter; Wieczorek, Edyta; Jabłońska, Ewa; Reszka, Edyta; Morawiec, Zbigniew; Wąsowicz, Wojciech; Gromadzińska, Jolanta

2018-01-01

The aim of this study was to establish whether the gene expression of estrogen receptor alpha (encoded by ESR1) correlates with the expression of glutathione peroxidase 1 (encoded by GPX1) in the tumor and adjacent tumor-free breast tissue, and whether this correlation is affected by breast cancer. Such relationships may give further insights into breast cancer pathology with respect to the status of estrogen receptor. We used the quantitative real-time PCR technique to analyze differences in the expression levels of the ESR1 and GPX1 genes in paired malignant and non-malignant tissues from breast cancer patients. ESR1 and GPX1 expression levels were found to be significantly down-regulated by 14.7% and 7.4% (respectively) in the tumorous breast tissue when compared to the non-malignant one. Down-regulation of these genes was independent of the tumor histopathology classification and clinicopathological factors, while the ESR1 mRNA level was reduced with increasing tumor grade (G1: 103% vs. G2: 85.8% vs. G3: 84.5%; p<0.05). In the non-malignant and malignant breast tissues, the expression levels of ESR1 and GPX1 were significantly correlated with each other (Rs=0.450 and Rs=0.360; respectively). Our data suggest that down-regulation of ESR1 and GPX1 was independent of clinicopathological factors. Down-regulation of ESR1 gene expression was enhanced by the development of the disease. Moreover, GPX1 and ESR1 gene expression was interdependent in the malignant breast tissue and further work is needed to determine the mechanism underlying this relationship.

Evaluation of serum cathepsin B and D in relation to clinicopathological staging of colorectal cancer

PubMed Central

Skrzydlewska, Elzbieta; Sulkowska, Mariola; Wincewicz, Andrzej; Koda, Mariusz; Sulkowski, Stanislaw

2005-01-01

AIM: Proteolytic degradation of the extracellular matrix facilitates cancer invasion and promotes metastasis. The study aims at evaluation of preoperative and postoperative serum cathepsins B and D levels in correlation with selected anatomoclinical features of colorectal cancer. METHODS: Blood samples were collected from 63 colorectal cancer patients before curative operation of the tumor 10 d later. Blood that was obtained from 20 healthy volunteers, served as a control. The activity of cathepsin B was measured with Bz-DL-arginine-pNA as a substrate at pH 6.0, while cathepsin D activity was determined with urea-denatured hemoglobin (pH 4.0). RESULTS: The preoperative and postoperative activities of cathepsin B were significantly (P < 0.00001) lower in serum of colorectal cancer patients than in control group. However, postoperative values of this protease were significantly increased in comparison with preoperative ones (P = 0.031). Activity of cathepsin D appeared to be significantly higher in colorectal cancer sera (P < 0.00001) compared with controls. No statistically significant differences between preoperative and postoperative activity of cathepsin D were noted (P = 0.09). We revealed a strong linkage of cathepsins’ levels with lymph node status and pT stage of colorectal cancer. CONCLUSION: Blood serum activities of cathepsin B and D depend on the time of sampling, tumor size and lymph node involvement. Significantly, increased activity of cathepsin D could indicate a malignant condition of the large intestine. In our work, the serum postoperative decrease of cathepsin B activity appears as an obvious concomitant of local lymph node metastasis-the well-known clinicopathological feature of poor prognosis. PMID:16015694

Nuclear C-MYC expression level is associated with disease progression and potentially predictive of two year overall survival in prostate cancer.

PubMed

Zeng, Wen; Sun, Hanying; Meng, Fankai; Liu, Zeming; Xiong, Jing; Zhou, Sheng; Li, Fan; Hu, Jia; Hu, Zhiquan; Liu, Zheng

2015-01-01

Upregulation of nuclear C-MYC protein has been reported to be an early event in prostate cancer (PCa); however, its clinicopathological and prognostic significance remain controversial. We determined the association of nuclear C-MYC protein expression with clinicopathological parameters, prognosis, ETS-related gene (ERG) expression, and TMPRSS2-ERG status in PCa. Nuclear C-MYC and ERG expression by immunohistochemistry and TMPRSS2-ERG status by triple-color probe fluorescence in situ hybridization assay were determined in 50 hormone-naïve PCa patients and 31 radical prostatectomy specimens. Nuclear C-MYC immunostaining was negative, positive, and strong positive in 27.5%, 32.5%, and 40.0% of cases, respectively. C-MYC immunostaining was significantly associated with clinical T stage (P < 0.001), distant metastasis at the time of diagnosis (P < 0.001) and TMPRSS2-ERG status (P = 0.001) but not with ERG immunostaining (P = 0.818). In the Kaplan-Meier analysis, C-MYC positive cases were found to have worse 2-year OS compared with C-MYC negative cases (P = 0.027). However, in the univariate Cox analysis, only TMPRSS2-ERG status (hazard ratio [HR] 0.189, 95% CI 0.057-0.629; P = 0.007) and distant metastasis (HR 3.545, 95% CI 1.056-11.894; P = 0.040) were significantly associated with 2-year OS. After adjusting for these two factors, TMPRSS2-ERG status still impacted 2-year OS (HR 0.196, 95% CI 0.049-0.778; P = 0.020). Nuclear C-MYC overexpression may be associated with disease progression and potentially predictive of 2-year OS in PCa. This is the first study to demonstrate an association between nuclear C-MYC immunostaining and TMPRSS2-ERG status in PCa.

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review

PubMed Central

Watanabe, Junko; Togo, Shinsaku; Sumiyoshi, Issei; Namba, Yukiko; Suina, Kentaro; Mizuno, Takafumi; Kadoya, Kotaro; Motomura, Hiroaki; Iwai, Moe; Nagaoka, Tetsutaro; Sasaki, Shinichi; Hayashi, Takuo; Uekusa, Toshimasa; Abe, Kanae; Urata, Yasuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Kato, Shunsuke; Takahashi, Kazuhisa

2018-01-01

Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement (p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC (p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome. PMID:29844868

Poor Prognosis of Lower Inner Quadrant in Lymph Node-negative Breast Cancer Patients Who Received No Chemotherapy: A Study Based on Nationwide Korean Breast Cancer Registry Database.

PubMed

Hwang, Ki-Tae; Kim, Jongjin; Kim, Eun-Kyu; Jung, Sung Hoo; Sohn, Guiyun; Kim, Seung Il; Jeong, Joon; Lee, Hyouk Jin; Park, Jin Hyun; Oh, Sohee

2017-07-01

We aimed to investigate the prognostic influence of primary tumor site on the survival of patients with breast cancer. Data of 63,388 patients with primary breast cancer from the Korean Breast Cancer Registry were analyzed. Primary tumor sites were classified into 5 groups: upper outer quadrant, lower outer quadrant, upper inner quadrant, lower inner quadrant (LIQ), and central portion. We analyzed overall survival (OS) and breast cancer-specific survival (BCSS) according to primary tumor site. Central portion and LIQ showed lower survival rates regarding both OS and BCSS compared with the other 3 quadrants (all P < .05) and hazard ratios were 1.267 (95% CI, 1.180-1.360, P < .001) and 1.215 (95% CI, 1.097-1.345, P < .001), respectively. Although central portion showed more unfavorable clinicopathologic features, LIQ showed more favorable features than the other 3 quadrants. Primary tumor site was a significant factor in univariate and multivariate analyses for OS and BCSS (all P < .001). For lymph node-negative patients, LIQ showed a worse OS than the other primary tumor sites in the subgroup with no chemotherapy (P < .001), but that effect disappeared in the subgroup with chemotherapy (P = .058). LIQ showed a worse prognosis despite having more favorable clinicopathologic features than other tumor locations and it was more prominent for lymph node-negative patients who received no chemotherapy. The hypothesis of possible hidden internal mammary node metastasis could be suggested to play a key role in LIQ lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

Upper Tract Urothelial Carcinomas Accompanied by Previous or Synchronous Nonmuscle-Invasive Bladder Cancer and Preoperative Hydronephrosis Might Have Worse Oncologic Outcomes After Radical Nephroureterectomy.

PubMed

Liang, Chengcai; Chi, Runmin; Huang, Liqun; Wang, Jinliang; Liu, Hailong; Xu, Ding; Qian, Subo; Qian, Xiaoqiang; Qi, Jun

2016-10-01

The purpose of the study was to identify predictors of clinicopathologic features and oncologic outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy (RNU). The medical records of 172 patients treated with RNU from January 2001 to September 2014 were retrospectively reviewed. Logistic regression and survival analysis methodology were respectively used to evaluate predictors of clinicopathologic features and oncologic outcomes. Of the enrolled 172 patients, 80 (46.5%) had renal pelvic tumors, 67 (39%) had ureteral tumors, and the remaining 25 (14.5%) patients had multifocal tumors. Compared with patients with renal pelvic tumors, those with ureteral and multifocal tumors were more likely to have previous or synchronous nonmuscle-invasive bladder cancer (NMIBC) and severe hydronephrosis (P = .001 and P < .001, respectively). Logistic regression analysis showed that previous or synchronous NMIBC was significantly associated with worse renal function and high grade (P = .034 and P = .014, respectively), and severe hydronephrosis independently predicted worse renal function and positive lymph node or lymphovascular invasion status (P = .001 and P = .007, respectively). Moreover, severe hydronephrosis was an independent risk factor for overall survival and cancer-specific survival in multivariate analysis (P = .025 and P = .045, respectively). Multifocality and previous or synchronous NMIBC were significantly associated with bladder-recurrence-free survival (P = .023 and P = .001, respectively). Upper tract urothelial carcinoma accompanied by previous or synchronous NMIBC and preoperative severe hydronephrosis could have worse oncologic outcomes after RNU. These common accompanied diagnoses could be valuable for guiding preoperative planning and postoperative adjuvant therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

The prognostic value of family history among patients with urinary bladder cancer.

PubMed

Egbers, Lieke; Grotenhuis, Anne J; Aben, Katja K; Alfred Witjes, J; Kiemeney, Lambertus A; Vermeulen, Sita H

2015-03-01

A history of urinary bladder cancer (UBC) in first-degree relatives increases UBC risk by twofold. The influence of positive family history on UBC prognosis is unknown. Here, we investigated association of first-degree UBC family history with clinicopathological characteristics and prognosis of UBC patients. Detailed clinical data of 1,465 non-muscle-invasive bladder cancer (NMIBC) and 250 muscle-invasive or metastatic bladder cancer (MIBC) patients, diagnosed from 1995 to 2010, were collected through medical file review. Competing risk analyses were used to compare recurrence-free survival (RFS) and progression-free survival (PFS) of NMIBC patients according to self-reported UBC family history. Overall survival in MIBC patients was estimated using Kaplan-Meier analysis. The added value of family history in prediction of NMIBC prognosis was quantified with Harrell's concordance-index. Hundred (6.8%) NMIBC and 14 (5.6%) MIBC patients reported UBC in first-degree relatives. Positive family history was statistically significantly associated with smaller tumor size and non-significantly with more favorable distribution of other tumor characteristics. In univariable analyses, positive family history correlated with longer RFS (p = 0.11) and PFS (p = 0.04). Hazard ratios for positive vs. negative family history after adjustment for clinicopathological characteristics were 0.75 (95% CI = 0.53-1.07) and 0.45 (95% CI = 0.18-1.12) for RFS and PFS, respectively. Five familial and 48 sporadic MIBC patients (Kaplan-Meier 10-year risk: 41% and 25%) died within 10 years. Family history did not improve the c-index of prediction models. This study shows that a first-degree family history of UBC is not clearly associated with NMIBC prognosis. Family history does not aid in prediction of NMIBC recurrence or progression. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Racial differences in the outcome of patients with urothelial carcinoma of the upper urinary tract: an international study.

PubMed

Matsumoto, Kazumasa; Novara, Giacomo; Gupta, Amit; Margulis, Vitaly; Walton, Thomas J; Roscigno, Marco; Ng, Casey; Kikuchi, Eiji; Zigeuner, Richard; Kassouf, Wassim; Fritsche, Hans-Martin; Ficarra, Vincenzo; Martignoni, Guido; Tritschler, Stefan; Rodriguez, Joaquin Carballido; Seitz, Christian; Weizer, Alon; Remzi, Mesut; Raman, Jay D; Bolenz, Christian; Bensalah, Karim; Koppie, Theresa M; Karakiewicz, Pierre I; Wood, Christopher G; Montorsi, Francesco; Iwamura, Masatsugu; Shariat, Shahrokh F

2011-10-01

•To assess the impact of differences in ethnicity on clinico-pathological characteristics and outcomes of patients with upper urinary tract urothelial carcinoma (UTUC) in a large multi-center series of patients treated with radical nephroureterectomy (RNU). •We retrospectively collected the data of 2163 patients treated with RNU at 20 academic centres in America, Asia, and Europe. •Univariable and multivariable Cox regression models addressed recurrence-free survival (RFS) and cancer-specific survival (CSS). •In all, 1794 (83%) patients were Caucasian and 369 (17%) were Japanese. All the main clinical and pathological features were significantly different between the two ethnicities. •The median follow-up of the whole cohort was 36 months. At last follow-up, 554 patients (26%) developed disease recurrence and 461 (21%) were dead from UTUC. •The 5-year RFS and CSS estimates were 71.5% and 74.2%, respectively, for Caucasian patients compared with 68.8% and 75.4%, respectively, for Japanese patients. •On univariable Cox regression analyses, ethnicity was not significantly associated with either RFS (P= 0.231) or CSS (P= 0.752). •On multivariable Cox regression analyses that adjusted for the effects of age, gender, surgical type, T stage, grade, tumour architecture, presence of concomitant carcinoma in situ, lymphovascular invasion, tumour necrosis, and lymph node status, ethnicity was not associated with either RFS (hazard ratio [HR] 1.1; P= 0.447) or CSS (HR 1.0; P= 0.908). •There were major differences in the clinico-pathological characteristics of Caucasian and Japanese patients. •However, RFS and CSS probabilities were not affected by ethnicity and race was not an independent predictor of either recurrence or cancer-related death. © 2011 THE AUTHORS; BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.

Suppression of RRM2 inhibits cell proliferation, causes cell cycle arrest and promotes the apoptosis of human neuroblastoma cells and in human neuroblastoma RRM2 is suppressed following chemotherapy.

PubMed

Li, Junfeng; Pang, Jinglin; Liu, Yongdong; Zhang, Jing; Zhang, Chuanguang; Shen, Gang; Song, Lili

2018-07-01

Ribonucleotide reductase regulatory subunit M2 (RRM2) is a rate‑limiting enzyme for DNA synthesis and repair. RRM2 has vital roles in controlling the progression of cancer. In the present study, we investigated the RRM2 level in neuroblastoma tissues, analyzed its relationship with clinicopathological characteristics of neuroblastoma patients, and explored the effect of RRM2 on the biological functions of neuroblastoma cells. RRM2 levels in 67 pairs of neuroblastoma and matched adjacent non‑cancerous tissues were detected by qRT‑PCR, and its association with patient clinicopathological features was assessed. Using RRM2 siRNA, the role of RRM2 in cell viability was detected by CCK‑8 assay, and the effects on cell cycle distribution and cell apoptosis were detected by flow cytometry. Hoechst 33342 staining was also performed. For RRM2 protein detection in cells and tissues, western blot analyses were employed. Our results revealed that RRM2 expression was significant higher in neuroblastoma tissues than that noted in adjacent non‑cancerous tissues at both the mRNA and protein levels. The increased RRM2 level was significantly associated with clinical stage. RRM2 levels were suppressed in stage III and IV tumors in the chemotherapy subgroup, compared with levels noted in tumors in the preoperative non‑chemotherapy subgroup. RRM2 siRNA significantly inhibited cell viability in the SH‑5Y5Y cells, induced cell arrest in the G0/G1 phase, and enhanced cell apoptosis. Taken together, overexpression of RRM2 is associated with the genesis and progression of neuroblastoma, and may be a potential chemotherapeutic target.

Mutation analysis of 13 driver genes of colorectal cancer-related pathways in Taiwanese patients

PubMed Central

Chang, Yuli Christine; Chang, Jan-Gowth; Liu, Ta-Chih; Lin, Chien-Yu; Yang, Shu-Fen; Ho, Cheng-Mao; Chen, William Tzu-Liang; Chang, Ya-Sian

2016-01-01

AIM: To investigate the driver gene mutations associated with colorectal cancer (CRC) in the Taiwanese population. METHODS: In this study, 103 patients with CRC were evaluated. The samples consisted of 66 men and 37 women with a median age of 59 years and an age range of 26-86 years. We used high-resolution melting analysis (HRM) and direct DNA sequencing to characterize the mutations in 13 driver genes of CRC-related pathways. The HRM assays were conducted using the LightCycler® 480 Instrument provided with the software LightCycler® 480 Gene Scanning Software Version 1.5. We also compared the clinicopathological data of CRC patients with the driver gene mutation status. RESULTS: Of the 103 patients evaluated, 73.79% had mutations in one of the 13 driver genes. We discovered 18 novel mutations in APC, MLH1, MSH2, PMS2, SMAD4 and TP53 that have not been previously reported. Additionally, we found 16 de novo mutations in APC, BMPR1A, MLH1, MSH2, MSH6, MUTYH and PMS2 in cancerous tissues previously reported in the dbSNP database; however, these mutations could not be detected in peripheral blood cells. The APC mutation correlates with lymph node metastasis (34.69% vs 12.96%, P = 0.009) and cancer stage (34.78% vs 14.04%, P = 0.013). No association was observed between other driver gene mutations and clinicopathological features. Furthermore, having two or more driver gene mutations correlates with the degree of lymph node metastasis (42.86% vs 24.07%, P = 0.043). CONCLUSION: Our findings confirm the importance of 13 CRC-related pathway driver genes in the development of CRC in Taiwanese patients. PMID:26900293

Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

PubMed

Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

2008-01-07

To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathological features. By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

Expression of Oct-4 is significantly associated with the development and prognosis of colorectal cancer

PubMed Central

ZHOU, HUAN; HU, YU; WANG, WEIPENG; MAO, YONG; ZHU, JINGJIE; ZHOU, BIN; SUN, JING; ZHANG, XUEGUANG

2015-01-01

Octamer-binding transcription factor 4 (Oct-4), is an essential transcription factor, which is required for pluripotency and self-renewal in embryonic stem cells and germ cells. It is also involved in maintaining cancer stem-like properties in certain types of tumor, and is an important biomarker for cancer stem cells. The present study investigated whether Oct-4 expression was associated with colorectal cancer (CRC). In order to achieve this, primary CRC tissues, matched non-tumor tissues and benign polyp tissues, representing different stages of carcinogenesis, were obtained, and Oct-4 expression was analyzed using reverse transcription-quantitative polymerase chain reaction, flow cytometry analysis and immunohistochemistry. Furthermore, the medical records of patients with CRC were reviewed, and clinicopathological analysis was performed in order to assess the association between Oct-4 expression and certain clinicopathological parameters. It was shown that the transcription and translation of Oct-4 increased in a stepwise manner, from non-tumor to benign polyp tissues, and from benign polyps to CRC tissues. Oct-4 expression in CRC was significantly correlated with histological grade (P=0.007), lymph node metastasis (P=0.027), distant metastasis (P=0.017) and TNM stage (P=0.041). Kaplan-Meier survival curve analysis demonstrated that Oct-4+ cases had a shorter median survival time (37.0 months) compared with Oct-4− cases (76.0 months; P=0.001). These results indicated that aberrant expression of Oct-4 may be involved in the development of CRC. Thus, Oct-4 may be a biomarker for the prediction, diagnosis or assessment of prognosis in CRC, in addition to a potential target for the treatment of this disease. PMID:26622555

Impact of free tumor clusters on prognosis after resection of pulmonary adenocarcinoma.

PubMed

Morimoto, Junichi; Nakajima, Takahiro; Suzuki, Hidemi; Nagato, Kaoru; Iwata, Takekazu; Yoshida, Shigetoshi; Fukuyo, Masaki; Ota, Satoshi; Nakatani, Yukio; Yoshino, Ichiro

2016-07-01

Pulmonary adenocarcinoma with a micropapillary component (MPC) has aggressive malignant behavior even if resectable. The aim of this study was to determine clinicopathologic features of patients who underwent surgery for pulmonary adenocarcinoma harboring MPCs, with particular focus on coexistent free tumor clusters (FTCs). We retrospectively reviewed 444 patients with pulmonary adenocarcinoma who underwent surgery from March 2007 to July 2013. An MPC was defined as a >5% micropapillary pattern. We also defined FTCs to be a group of more than 3 small clusters containing <20 nonintegrated micropapillary tumor cells that were spreading within air spaces, >3 mm apart from the main tumor. The clinicopathologic characteristics of patients with and without FTCs were retrospectively investigated in MPC-positive patients. MPCs were identified in 67 patients (15.1%), 31 of whom (46.3%) were positive for FTCs. The distance between the furthest edge of FTCs and main tumors did not exceed the diameter of the main tumor in each case (average, 7.3 mm). Locoregional recurrences were frequently observed in FTC-positive patients. FTC-positive patients experienced a significantly lower 5-year recurrence-free survival rate compared with FTC-negative/MPC-positive patients (20.4% vs 52.2%, P < .001). Recurrence-free survival of FTC-negative and -positive patients was equivalent to that of patients with p-T2 and p-T3 MPC-negative adenocarcinoma, respectively. Coexistence of FTCs resulted in a further negative impact on postoperative prognosis among MPC-positive adenocarcinomas and should be considered for upstaging the p-T factor and during evaluation of surgical margins. Copyright © 2016. Published by Elsevier Inc.

Mutation analysis of 13 driver genes of colorectal cancer-related pathways in Taiwanese patients.

PubMed

Chang, Yuli Christine; Chang, Jan-Gowth; Liu, Ta-Chih; Lin, Chien-Yu; Yang, Shu-Fen; Ho, Cheng-Mao; Chen, William Tzu-Liang; Chang, Ya-Sian

2016-02-21

To investigate the driver gene mutations associated with colorectal cancer (CRC) in the Taiwanese population. In this study, 103 patients with CRC were evaluated. The samples consisted of 66 men and 37 women with a median age of 59 years and an age range of 26-86 years. We used high-resolution melting analysis (HRM) and direct DNA sequencing to characterize the mutations in 13 driver genes of CRC-related pathways. The HRM assays were conducted using the LightCycler® 480 Instrument provided with the software LightCycler® 480 Gene Scanning Software Version 1.5. We also compared the clinicopathological data of CRC patients with the driver gene mutation status. Of the 103 patients evaluated, 73.79% had mutations in one of the 13 driver genes. We discovered 18 novel mutations in APC, MLH1, MSH2, PMS2, SMAD4 and TP53 that have not been previously reported. Additionally, we found 16 de novo mutations in APC, BMPR1A, MLH1, MSH2, MSH6, MUTYH and PMS2 in cancerous tissues previously reported in the dbSNP database; however, these mutations could not be detected in peripheral blood cells. The APC mutation correlates with lymph node metastasis (34.69% vs 12.96%, P = 0.009) and cancer stage (34.78% vs 14.04%, P = 0.013). No association was observed between other driver gene mutations and clinicopathological features. Furthermore, having two or more driver gene mutations correlates with the degree of lymph node metastasis (42.86% vs 24.07%, P = 0.043). Our findings confirm the importance of 13 CRC-related pathway driver genes in the development of CRC in Taiwanese patients.

Combination immunohistochemistry for SMAD4 and Runt-related transcription factor 3 may identify a favorable prognostic subgroup of pancreatic ductal adenocarcinomas.

PubMed

Lee, Yangkyu; Lee, Hyejung; Park, Hyunjin; Kim, Jin-Won; Hwang, Jin-Hyeok; Kim, Jaihwan; Yoon, Yoo-Seok; Han, Ho-Seong; Kim, Haeryoung

2017-09-29

SMAD4/DPC4 mutations have been associated with aggressive behavior in pancreatic ductal adenocarcinomas (PDAC), and it has recently been suggested that RUNX3 expression combined with SMAD4 status may predict the metastatic potential of PDACs. We evaluated the prognostic utility of SMAD4/RUNX3 status in human PDACs by immunohistochemistry. Immunohistochemical stains were performed for SMAD4 and RUNX3 on 210 surgically resected PDACs, and the results were correlated with the clinicopathological features. Loss of SMAD4 expression was associated with poor overall survival (OS) ( p = 0.015) and progression-free survival (PFS) ( p = 0.044). Nuclear RUNX3 expression was associated with decreased OS ( p = 0.010) and PFS ( p = 0.009), and more frequent in poorly differentiated PDACs ( p = 0.037). On combining RUNX3/SMAD4 status, RUNX3-/SMAD4+ PDACs demonstrated longer OS ( p = 0.008, median time; RUNX3-/SMAD4+ 34 months, others 17 months) and PFS ( p = 0.009, median time; RUNX3-/SMAD4+ 29 months, others 8 months) compared to RUNX3+/SMAD4+ and SMAD4- groups; RUNX3-/SMAD4+ was a significant independent predictive factor for both OS [ p = 0.025, HR 1.842 (95% CI 1.079-3.143)] and PFS [ p = 0.020, HR 1.850 (95% CI 1.100-3.113)]. SMAD4-positivity with RUNX3-negativity was a significant independent predictive factor for favorable OS and PFS in PDAC. This is the first and large clinicopathological study of RUNX3/SMAD4 expression status in human PDAC. Combination immunohistochemistry for SMAD4 and RUNX3 may help identify a favorable prognostic subgroup of PDAC.

Combination immunohistochemistry for SMAD4 and Runt-related transcription factor 3 may identify a favorable prognostic subgroup of pancreatic ductal adenocarcinomas

PubMed Central

Lee, Yangkyu; Lee, Hyejung; Park, Hyunjin; Kim, Jin-Won; Hwang, Jin-Hyeok; Kim, Jaihwan; Yoon, Yoo-Seok; Han, Ho-Seong; Kim, Haeryoung

2017-01-01

Purposes SMAD4/DPC4 mutations have been associated with aggressive behavior in pancreatic ductal adenocarcinomas (PDAC), and it has recently been suggested that RUNX3 expression combined with SMAD4 status may predict the metastatic potential of PDACs. We evaluated the prognostic utility of SMAD4/RUNX3 status in human PDACs by immunohistochemistry. Materials and Methods Immunohistochemical stains were performed for SMAD4 and RUNX3 on 210 surgically resected PDACs, and the results were correlated with the clinicopathological features. Results Loss of SMAD4 expression was associated with poor overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.044). Nuclear RUNX3 expression was associated with decreased OS (p = 0.010) and PFS (p = 0.009), and more frequent in poorly differentiated PDACs (p = 0.037). On combining RUNX3/SMAD4 status, RUNX3-/SMAD4+ PDACs demonstrated longer OS (p = 0.008, median time; RUNX3-/SMAD4+ 34 months, others 17 months) and PFS (p = 0.009, median time; RUNX3-/SMAD4+ 29 months, others 8 months) compared to RUNX3+/SMAD4+ and SMAD4- groups; RUNX3-/SMAD4+ was a significant independent predictive factor for both OS [p = 0.025, HR 1.842 (95% CI 1.079-3.143)] and PFS [p = 0.020, HR 1.850 (95% CI 1.100-3.113)]. Conclusions SMAD4-positivity with RUNX3-negativity was a significant independent predictive factor for favorable OS and PFS in PDAC. This is the first and large clinicopathological study of RUNX3/SMAD4 expression status in human PDAC. Combination immunohistochemistry for SMAD4 and RUNX3 may help identify a favorable prognostic subgroup of PDAC. PMID:29100342

MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4

PubMed Central

Zhang, Kundong; Cen, Gang; Jiang, Tao; Cao, Jun; Huang, Kejian; Zhao, Qian; Qiu, Zhengjun

2015-01-01

Background Aim to determine the clinicopathological and prognostic role of miR-301a-3p in pancreatic ductal adenocarcinoma(PDAC), to investigate the biological mechanism of miR-301a-3p in vitro and in vivo. Methods By tissue microarray analysis, we studied miR-301a-3p expression in PDAC patients and its clinicopathological correlations as well as prognostic significance. qRT-PCR was used to test miR-301a-3p expression in PDAC tissues and cell lines. Functional experiments including in vitro and in vivo were performed. Results Significantly higher expression of miR-301a-3p were found in PDAC patients with lymph node metastasis and advanced pathological stages and identified as an independent prognostic factor for worse survival. In PDAC samples and cell lines, miR-301a-3p was significantly up-regulated compared with matched non-tumor tissues and normal pancreatic ductal cells, respectively. Overexpression of miR-301a-3p enhanced PDAC cells colony, invasion and migration abilities in vitro as well as tumorigenicity in vivo. Furthermore, SMAD4 was identified as a target gene of miR-301a-3p by cell as well as mice xenograft experiments. In PDAC tissue microarray, a significantly inverse correlation between miR-301a-3p ISH scores and SMAD4 IHC scores were observed in both tumor and corresponding non-tumor tissues. Conclusion MiR-301a-3p functions as a novel oncogene in PDAC and the oncogenic activity may involve its inhibition of the target gene SMAD4. PMID:26019136

Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.

PubMed

Watanabe, Junko; Togo, Shinsaku; Sumiyoshi, Issei; Namba, Yukiko; Suina, Kentaro; Mizuno, Takafumi; Kadoya, Kotaro; Motomura, Hiroaki; Iwai, Moe; Nagaoka, Tetsutaro; Sasaki, Shinichi; Hayashi, Takuo; Uekusa, Toshimasa; Abe, Kanae; Urata, Yasuo; Sakurai, Fuminori; Mizuguchi, Hiroyuki; Kato, Shunsuke; Takahashi, Kazuhisa

2018-05-08

Anti-anaplastic lymphoma kinase (ALK)-targeted therapy dramatically improves therapeutic responses in patients with ALK-rearranged lung adenocarcinoma (Ad-LC). A few cases of squamous cell lung carcinoma (Sq-LC) with ALK rearrangement have been reported; however, the clinicopathological features and clinical outcomes following treatment with ALK inhibitors are unknown. We addressed this in the present study by retrospectively comparing the clinical characteristics of five patients with ALK-rearranged Sq-LC with those of patients with ALK-rearranged Ad-LC and by evaluating representative cases of ALK inhibitor responders and non-responders. The prevalence of ALK rearrangement in Sq-LCs was 1.36%. Progression-free survival (PFS) after initial treatment with crizotinib was significantly shorter in Sq-LC than in Ad-LC with ALK rearrangement ( p = 0.033). Two ALK rearrangements assayed by fluorescence in situ hybridization (FISH)-positive/immunohistochemistry-negative cases did not respond to crizotinb, and PFS decreased following alectinib treatment of ALK-rearranged Sq-LC ( p = 0.045). A rebiopsy revealed that responders to ceritinib harbored the L1196M mutation, which causes resistance to other ALK inhibitors. However, non-responders were resistant to all ALK inhibitors, despite the presence of ALK rearrangement in FISH-positive circulating tumor cells and circulating free DNA and absence of the ALK inhibitor resistance mutation. These results indicate that ALK inhibitors remain a reasonable therapeutic option for ALK-rearranged Sq-LC patients who have worse outcomes than ALK-rearranged Ad-LC patients and that resistance mechanisms are heterogeneous. Additionally, oncologists should be aware of the possibility of ALK-rearranged Sq-LC based on clinicopathological features, and plan second-line therapeutic strategies based on rebiopsy results in order to improve patient outcome.

Colorectal Carcinomas With Isolated Loss of PMS2 Staining by Immunohistochemistry.

PubMed

Alpert, Lindsay; Pai, Reetesh K; Srivastava, Amitabh; McKinnon, Wendy; Wilcox, Rebecca; Yantiss, Rhonda K; Arcega, Ramir; Wang, Hanlin L; Robert, Marie E; Liu, Xiuli; Pai, Rish K; Zhao, Lei; Westerhoff, Maria; Hampel, Heather; Kupfer, Sonia; Setia, Namrata; Xiao, Shu-Yuan; Hart, John; Frankel, Wendy L

2018-04-01

- Isolated loss of PMS2 staining is an uncommon immunophenotype in colorectal carcinomas, accounting for approximately 4% of tumors with microsatellite instability. Limited information regarding these tumors is available in the literature. - To compare the clinicopathologic features of colorectal carcinomas with isolated PMS2 loss by immunohistochemistry to those with other forms of mismatch repair deficiency. - Ninety-three colorectal carcinomas with isolated PMS2 loss by immunohistochemistry and 193 with other forms of mismatch repair deficiency were identified. Forty (43%) of the isolated PMS2 loss cases and 35 control cases (18%) had a known germline mutation or a clinical diagnosis of Lynch syndrome. - Overall, isolated PMS2-loss tumors occurred in significantly younger patients ( P < .001) and in fewer female patients ( P = .006). These tumors were significantly less likely to be right-sided ( P = .001), high-grade ( P = .01), or display histologic features of microsatellite instability ( P < .001). The isolated PMS2-loss group also exhibited increased odds of disease-specific death (odds ratio [OR], 3.09; 95% CI, 1.41-6.85; P = .007). When the analysis was restricted to germline mutation/Lynch syndrome cases and controls, no significant differences were detected for age, sex, tumor location, tumor grade, histologic features, or distant metastases, although a trend toward increased odds of disease-specific death in the isolated PMS2-loss group was evident (OR, 3.87; 95% CI, 0.89-27.04; P = .10). - Unusual clinicopathologic features observed in colorectal carcinomas with isolated PMS2 loss are likely related to the high proportion of cases caused by germline mutations. Isolated PMS2-loss tumors may demonstrate more aggressive behavior than other tumors with microsatellite instability, but larger studies are needed to investigate that possibility further.

The associations of genetic polymorphisms in CYP1A2 and CYP3A4 with clinical outcomes of breast cancer patients in northern China

PubMed Central

Bai, Xianan; Xie, Jingjing; Sun, Shanshan; Zhang, Xianyu; Jiang, Yongdong; Pang, Da

2017-01-01

Background Cytochrome P450 (CYP) 1A2 and CYP3A4 may play a role in the differentiation of clinical outcomes among breast cancer women. This study aimed to analyze the association of genetic polymorphisms in the CYP1A2 and CYP3A4 genes with clinicopathological features, protein expression and prognosis of breast cancer in the northern Chinese population. Results Firstly, SNP rs11636419, rs17861162 and rs2470890 in the CYP1A2 were significantly associated with age and menstruation status. And SNP rs11636419 and rs17861162 were associated with the P53 status. Secondly, SNP rs2470890 was correlated with CYP1A2 protein expression under the co-dominant and dominant model (P = 0.017, P = 0.006, respectively). Thirdly, for SNP rs2470890, the Kaplan–Meier 5 year survival curves showed that patients carrying genotypes CT or TT had a worse OS compared with the genotype CC carriers under both codominant and dominant model (P < 0.001, P < 0.001, respectively). Materials and Methods Four single nucleotide polymorphisms (SNPs) were successfully genotyped in 459 breast cancer patients using the SNaPshot method. The associations of four polymorphisms with protein expression and clinicopathological characteristics were evaluated by Pearson's chi-square test. The Cox hazard regression analysis and Kaplan–Meier survival analysis were performed to evaluate the relationship between the SNPs and overall survival (OS) of breast cancer. Conclusions CYP1A2 rs2470890 was significantly associated with the prognosis of patients with breast cancer and could serve as an independent impact factor of prognosis of breast carcinoma. PMID:28418906

MicroRNA-Related DNA Repair/Cell-Cycle Genes Independently Associated With Relapse After Radiation Therapy for Early Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gee, Harriet E., E-mail: harriet.gee@sydney.edu.au; The Chris O'Brien Lifehouse, Missenden Road, Camperdown, NSW; Central Clinical School, Sydney Medical School, University of Sydney, NSW

Purpose: Local recurrence and distant failure after adjuvant radiation therapy for breast cancer remain significant clinical problems, incompletely predicted by conventional clinicopathologic markers. We had previously identified microRNA-139-5p and microRNA-1274a as key regulators of breast cancer radiation response in vitro. The purpose of this study was to investigate standard clinicopathologic markers of local recurrence in a contemporary series and to establish whether putative target genes of microRNAs involved in DNA repair and cell cycle control could better predict radiation therapy response in vivo. Methods and Materials: With institutional ethics board approval, local recurrence was measured in a contemporary, prospectively collected series ofmore » 458 patients treated with radiation therapy after breast-conserving surgery. Additionally, independent publicly available mRNA/microRNA microarray expression datasets totaling >1000 early-stage breast cancer patients, treated with adjuvant radiation therapy, with >10 years of follow-up, were analyzed. The expression of putative microRNA target biomarkers—TOP2A, POLQ, RAD54L, SKP2, PLK2, and RAG1—were correlated with standard clinicopathologic variables using 2-sided nonparametric tests, and to local/distant relapse and survival using Kaplan-Meier and Cox regression analysis. Results: We found a low rate of isolated local recurrence (1.95%) in our modern series, and that few clinicopathologic variables (such as lymphovascular invasion) were significantly predictive. In multiple independent datasets (n>1000), however, high expression of RAD54L, TOP2A, POLQ, and SKP2 significantly correlated with local recurrence, survival, or both in univariate and multivariate analyses (P<.001). Low RAG1 expression significantly correlated with local recurrence (multivariate, P=.008). Additionally, RAD54L, SKP2, and PLK2 may be predictive, being prognostic in radiation therapy–treated patients but not in untreated matched control individuals (n=107; P<.05). Conclusions: Biomarkers of DNA repair and cell cycle control can identify patients at high risk of treatment failure in those receiving radiation therapy for early breast cancer in independent cohorts. These should be further investigated prospectively, especially TOP2A and SKP2, for which targeted therapies are available.« less

TFE3-Fusion Variant Analysis Defines Specific Clinicopathologic Associations Among Xp11 Translocation Cancers

PubMed Central

Argani, Pedram; Zhong, Minghao; Reuter, Victor E.; Fallon, John T.; Epstein, Jonathan I.; Netto, George J.; Antonescu, Cristina R.

2016-01-01

Xp11 translocation cancers include Xp11 translocation renal cell carcinoma (RCC), Xp11 translocation perivascular epithelioid cell tumor (PEComa), and melanotic Xp11 translocation renal cancer. In Xp11 translocation cancers, oncogenic activation of TFE3 is driven by the fusion of TFE3 with a number of different gene partners, however, the impact of individual fusion variant on specific clinicopathologic features of Xp11 translocation cancers has not been well defined. In this study, we analyze 60 Xp11 translocation cancers by fluorescence in situ hybridization (FISH) using custom BAC probes to establish their TFE3 fusion gene partner. In 5 cases RNA sequencing (RNA-seq) was also used to further characterize the fusion transcripts. The 60 Xp11 translocation cancers included 47 Xp11 translocation RCC, 8 Xp11 translocation PEComas, and 5 melanotic Xp11 translocation renal cancers. A fusion partner was identified in 53/60 (88%) cases, including 18 SFPQ (PSF), 16 PRCC, 12 ASPSCR1 (ASPL), 6 NONO, and 1 DVL2. We provide the first morphologic description of the NONO-TFE3 RCC, which frequently demonstrates sub-nuclear vacuoles leading to distinctive suprabasal nuclear palisading. Similar sub-nuclear vacuolization was also characteristic of SFPQ-TFE3 RCC, creating overlapping features with clear cell papillary RCC. We also describe the first RCC with a DVL2-TFE3 gene fusion, in addition to an extrarenal pigmented PEComa with a NONO-TFE3 gene fusion. Furthermore, among neoplasms with the SFPQ-TFE3, NONO-TFE3, DVL2-TFE3 and ASPL-TFE3 gene fusions, the RCC are almost always PAX8-positive, cathepsin K-negative by immunohistochemistry, whereas the mesenchymal counterparts (Xp11 translocation PEComas, melanotic Xp11 translocation renal cancers, and alveolar soft part sarcoma) are PAX8-negative, cathepsin K-positive. These findings support the concept that despite an identical gene fusion, the RCCs are distinct from the corresponding mesenchymal neoplasms, perhaps due to the cellular context in which the translocation occurs. We corroborate prior data showing that the PRCC-TFE3 RCC are the only known Xp11 translocation RCC molecular subtype which is consistently cathepsin K positive. In summary, our data expand further the clinicopathologic features of cancers with specific TFE3 gene fusions, and should allow for more meaningful clinicopathologic associations to be drawn. PMID:26975036

Detection of pAkt protein in imprint cytology of invasive breast cancer: Correlation with HER2/neu, hormone receptors, and other clinicopathological variables

PubMed Central

Vasou, Olympia; Skagias, Lazaros; Anastasia, Margariti; Paulina, Athanasiadou; Patsouris, Efstratios; Politi, Ekaterini

2015-01-01

Purpose: Akt is a serine/threonine protein kinase and has emerged as a crucial regulator of widely divergent cellular processes, including apoptosis, proliferation, differentiation, and metabolism. Activation of Akt/protein kinase B has been positively associated with human epidermal growth-factor receptor 2 (HER2)/neu overexpression in breast carcinoma and a worse outcome among endocrine treated patients. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Methods: Archival tumor tissues from 100 patients with invasive breast carcinoma were analyzed by immunocytochemistry. This study describes the results of immunocytochemical pAkt expression in breast carcinoma imprints, prepared from cut surfaces of freshly removed tumors. Both nuclear and cytoplasmic expressions were evaluated for pAkt. Results: Nuclear and cytoplasmic positive scores of 72% (72/100) and 42% (42/100), respectively, were found. Coexistence of nuclear and cytoplasmic staining was observed in 32 cases (32/100). Nuclear positive staining correlated with HER2/neu overexpression (P = 0.043) and was significantly associated with positive involvement of axillary lymph nodes (P = 0.013). No correlation was found between cytoplasmic pAkt rate and clinicopathological parameters, estrogen receptor, progesterone receptor or HER2/neu expression. Conclusions: pAkt expression can be evaluated in cytological material and may add valuable information to current prognostic models for breast cancer. pAkt overexpression appears to be linked with potentially aggressive tumor phenotype in invasive breast carcinoma. PMID:25838835

Breast cancer in young women in a limited-resource environment.

PubMed

Basro, Sarinah; Apffelstaedt, Justus P

2010-07-01

Despite the higher incidence of breast cancer in young women in developing countries, there is a paucity of data on their management. We present the clinicopathological features and outcome of treatment of women 35 years or younger with breast cancer in a resource-restricted environment. A total of 141 patients who were diagnosed with primary breast cancer at 35 years or younger from January 2000 to June 2008 were retrieved from the cancer registry of a breast clinic at a tertiary hospital and a private breast health center in South Africa. Clinicopathological features, treatment, and survival were analyzed. Two patients presented with TNM stage 0 (1.4%), 14 with stage I (9.9%), 47 with stage II (33.35%), 47 with stage III (33.3%), and 31 with stage IV (21.9%). Tumor grade was 3 in 47%, grade 2 in 37%, and grade 1 in 16% of patients. One hundred and four patients with stage 0-III disease underwent treatment with curative intent, 83 had a mastectomy, and 12 had breast-conserving surgery. Ninety patients (86.5%) had chemotherapy, 68 (65.4%) had radiotherapy, and 50 (48.1%) had hormonal therapy. Of 93 patients who completed primary therapy, 4 developed contralateral cancers, 3 had locoregional recurrence, 8 developed synchronous locoregional and distant recurrence, and 19 relapsed with distant metastasis only. The 2-year disease-free and overall survival for stage 0-III disease was 48 and 56%, respectively. Young women with breast cancer in a resource-limited environment have similar adverse clinicopathological features to those in developed countries. Their disease is more advanced at presentation with poorer outcome. Increased awareness, better systemic therapy, and more comprehensive genetic studies are essential to improve the dismal outcome.