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Sample records for independently significant prognostic

  1. Prognostic significance of QRS duration and morphology.

    PubMed

    Brenyo, Andrew; Zaręba, Wojciech

    2011-01-01

    QRS duration and morphology, evaluated via a standard 12-lead electrocardiogram (ECG), represent an opportunity to derive useful prognostic information regarding the risk of subsequent cardiac events or therapeutic outcomes. Prolonged QRS duration, and the presence of intraventricular conduction abnormalities, usually indicate the presence of changes in the myocardium due to underlying heart disease. Prolonged QRS duration is often associated with depressed ejection fraction or enlarged left ventricular volumes, but several studies have demonstrated that this simple ECG measure provides independent prognostic value, after adjusting for relevant clinical covariates. Post-infarction patients with prolonged QRS duration have a significantly increased risk of mortality, although data associating QRS prolongation specifically with sudden death is less supportive. In non-ischemic cardiomyopathy, there is no evidence that QRS duration has prognostic significance in predicting mortality or sudden death. Prolonged QRS duration, and especially presence of left bundle branch block, seems to predict a benefit from cardiac resynchronization therapy in both ischemic and non-ischemic cardiomyopathy patients. Therefore, QRS duration and morphology should not only be considered a predictor of death or sudden death in patients after myocardial infarction, and in those suspected of coronary artery disease, but also as a predictor of benefit from cardiac resynchronization therapy in patients with heart failure, whether of an ischemic or non-ischemic origin. PMID:21305480

  2. Vascular grading of angiogenesis: prognostic significance in breast cancer

    PubMed Central

    Hansen, S; Grabau, D A; Sørensen, F B; Bak, M; Vach, W; Rose, C

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11 years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers was moderately reproduced (κ = 0.59). Vascular grade was significantly associated with axillary node involvement, tumour size, malignancy grade, oestrogen receptor status and histological type. In univariate analyses vascular grade significantly predicted recurrence free survival and overall survival for all patients (P< 0.0001), node-negative patients (P< 0.0001) and node-positive patients (P< 0.0001). Cox multivariate regression analysis showed that vascular grading contributed with independent prognostic value in all patients (P< 0.0001). A prognostic index including the vascular grade had clinical impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer. © 2000 Cancer Research Campaign PMID:10646886

  3. Prognostic Significance of Imaging Myocardial Sympathetic Innervation.

    PubMed

    Malhotra, Saurabh; Fernandez, Stanley F; Fallavollita, James A; Canty, John M

    2015-08-01

    There has been a longstanding interest in understanding whether the presence of inhomogeneity in myocardial sympathetic innervation can predict patients at risk of sudden cardiac arrest from lethal ventricular arrhythmias. The advent of radiolabeled norepinephrine analogs has allowed this to be imaged in patients with ischemic and non-ischemic cardiomyopathy using single, photon emission computed tomography (SPECT) and positron emission tomography (PET). Several observational studies have demonstrated that globally elevated myocardial sympathetic tone (as reflected by reduced myocardial norepinephrine analog uptake) can predict composite cardiac end-points including total cardiovascular mortality. More recent studies have indicated that quantifying the extent of regional denervation can predict the risk of lethal ventricular arrhythmias and sudden cardiac death. This review will summarize our current understanding of the prognostic significance of altered myocardial sympathetic innervation. PMID:26087899

  4. The time frame of Epstein-Barr virus latent membrane protein-1 gene to disappear in nasopharyngeal swabs after initiation of primary radiotherapy is an independently significant prognostic factor predicting local control for patients with nasopharyngeal carcinoma

    SciTech Connect

    Lin, S.-Y.; Chang, K.-P.; Hsieh, M.-S.; Ueng, S.-H.; Hao, S.-P.; Tseng, C.-K.; Pai, P.-C.; Chang, F.-T.; Tsai, M.-H.; Tsang, N.-M. . E-mail: rt3126@adm.cgmh.org.tw

    2005-12-01

    Purpose: The presence of Epstein-Barr virus latent membrane protein-1 (LMP-1) gene in nasopharyngeal swabs indicates the presence of nasopharyngeal carcinoma (NPC) mucosal tumor cells. This study was undertaken to investigate whether the time taken for LMP-1 to disappear after initiation of primary radiotherapy (RT) was inversely associated with NPC local control. Methods and Materials: During July 1999 and October 2002, there were 127 nondisseminated NPC patients receiving serial examinations of nasopharyngeal swabbing with detection of LMP-1 during the RT course. The time for LMP-1 regression was defined as the number of days after initiation of RT for LMP-1 results to turn negative. The primary outcome was local control, which was represented by freedom from local recurrence. Results: The time for LMP-1 regression showed a statistically significant influence on NPC local control both univariately (p < 0.0001) and multivariately (p = 0.004). In multivariate analysis, the administration of chemotherapy conferred a significantly more favorable local control (p = 0.03). Advanced T status ({>=} T2b), overall treatment time of external photon radiotherapy longer than 55 days, and older age showed trends toward being poor prognosticators. The time for LMP-1 regression was very heterogeneous. According to the quartiles of the time for LMP-1 regression, we defined the pattern of LMP-1 regression as late regression if it required 40 days or more. Kaplan-Meier plots indicated that the patients with late regression had a significantly worse local control than those with intermediate or early regression (p 0.0129). Conclusion: Among the potential prognostic factors examined in this study, the time for LMP-1 regression was the most independently significant factor that was inversely associated with NPC local control.

  5. Prognostic significance of Tspan9 in gastric cancer

    PubMed Central

    Feng, Tongtong; Sun, Libin; Qi, Weiwei; Pan, Fei; Lv, Jing; Guo, Jing; Zhao, Shufen; Ding, Aiping; Qiu, Wensheng

    2016-01-01

    Tetraspanins are a large superfamily of glycoproteins, which are engaged in a wide range of specific molecular interactions by forming tetraspanin-enriched microdomains. Tetraspanin 9 (Tspan9) is a previously poorly studied tetraspanin gene, which was predominantly identified as an amplified gene in serous Fallopian tube carcinoma. However, the expression and role of Tspan9 in gastric cancer have yet to be fully elucidated. The aim of the present study was to evaluate the expression and clinical significance of Tspan9 in gastric cancer. In the present study, 105 gastric cancer tissue samples and corresponding adjacent normal samples were detected for Tspan9 expression using immunohistochemistry; furthermore, the association between clinical characteristics and Tspan9 expression was also analyzed. Tspan9 expression was determined to be significantly lower in cancer samples compared with those in corresponding adjacent normal samples (P<0.001). However, its increased levels of expression in cancer samples appeared to demonstrate a poorer prognostic tendency, which is associated with deeper tumor depth (P=0.025), more nodal involvement (P=0.01), more advanced tumor/lymph node/metastasis (TNM) stages (P=0.017) and a larger tumor size (P=0.026). Additionally, multivariate analysis demonstrated that high expression of Tspan9 was an independent prognostic factor for poor overall survival (P<0.01). These results suggested that Tspan9 may be used as a potential prognostic factor in gastric cancer.

  6. Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas

    PubMed Central

    Wang, Mo-Jin; Ping, Jie; Li, Yuan; Holmqvist, Annica; Adell, Gunnar; Arbman, Gunnar; Zhang, Hong; Zhou, Zong-Guang; Sun, Xiao-Feng

    2015-01-01

    Abstract Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973–2011), and Linköping Cancer (LC, 1972–2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; LC, P = 0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057–1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493–10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CI, 0.106–1.192; P = 0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients. PMID:26705231

  7. Prognostic significance of peripheral monocyte count in patients with extranodal natural killer/T-cell lymphoma

    PubMed Central

    2013-01-01

    Background Extranodal natural killer/T-cell lymphoma (ENKL) has heterogeneous clinical manifestations and prognosis. This study aims to evaluate the prognostic impact of absolute monocyte count (AMC) in ENKL, and provide some immunologically relevant information for better risk stratification in patients with ENKL. Methods Retrospective data from 163 patients newly diagnosed with ENKL were analyzed. The absolute monocyte count (AMC) at diagnosis was analyzed as continuous and dichotomized variables. Independent prognostic factors of survival were determined by Cox regression analysis. Results The AMC at diagnosis were related to overall survival (OS) and progression-free survival (PFS) in patients with ENKL. Multivariate analysis identified AMC as independent prognostic factors of survival, independent of International Prognostic Index (IPI) and Korean prognostic index (KPI). The prognostic index incorporating AMC and absolute lymphocyte count (ALC), another surrogate factor of immune status, could be used to stratify all 163 patients with ENKL into different prognostic groups. For patients who received chemotherapy followed by radiotherapy (102 cases), the three AMC/ALC index categories identified patients with significantly different survivals. When superimposed on IPI or KPI categories, the AMC/ALC index was better able to identify high-risk patients in the low-risk IPI or KPI category. Conclusion The baseline peripheral monocyte count is shown to be an effective prognostic indicator of survival in ENKL patients. The prognostic index related to tumor microenvironment might be helpful to identify high-risk patients with ENKL. PMID:23638998

  8. Prognostic Significance of Single Progesterone Receptor Positivity

    PubMed Central

    Fan, Ying; Ding, Xiaoyan; Xu, Binghe; Ma, Fei; Yuan, Peng; Wang, Jiayu; Zhang, Pin; Li, Qing; Luo, Yang

    2015-01-01

    Abstract Single progesterone receptor positive (PgR+), especially in form of ER−/PgR+/HER2−, is a nonnegligible phenomenon. Little is known about the characteristics and the role of single PgR positive in this phenotype. Therefore, we explore the significance of single PgR positivity by comparing ER−/PgR+/HER2− breast cancers with triple negative breast cancers (TNBCs). Three thousand nine hundred sixty-six cases of primary invasive breast carcinoma operated consecutively from January 2005 to May 2008 in Cancer Hospital, Chinese Academy of Medical Sciences were examined. Two hundred forty (6%) cases were identified as ER−/PgR+/HER2− breast cancers and 348 (8.8%) cases as TNBCs. Clinicopathological characteristics and survivals were analyzed respectively and then compared between 2 subtypes. Compared with patients with TNBCs, ER−/PgR+/HER2− tumor tended to have lower tumor grade (Grade 3: 45.7% vs. 37.5%, P = 0.051) and smaller tumor size (P = 0.036). However, no differences were found between ER−/PgR+/HER2− and TNBC patients in relapse-free survival (RFS) and OS. The 5-year RFS rates were 80.7% and 77.4%, respectively (P = 0.330) and the 5-year OS rates were 88.0% and 85.2%, respectively (P = 0.290). ER−/PgR+/HER2− patients receiving adjuvant endocrine treatment had better RFS (P = 0.016) and overall survival (OS) (P < 0.0001) than patients receiving no endocrine therapy. This exclusive analysis of patients with ER−/PgR+/HER2− breast cancers showed that this subtype exhibited an aggressive behavior as TNBC, suggesting that it should also be regarded as biologically distinctive group and single PgR positive itself is not a good prognostic factor. However, adjuvant endocrine therapy could still benefit this group of patients. Further investigations should be done to elucidate the underlying mechanism. PMID:26579819

  9. Exercise oscillatory ventilation: Mechanisms and prognostic significance

    PubMed Central

    Dhakal, Bishnu P; Lewis, Gregory D

    2016-01-01

    Alteration in breathing patterns characterized by cyclic variation of ventilation during rest and during exercise has been recognized in patients with advanced heart failure (HF) for nearly two centuries. Periodic breathing (PB) during exercise is known as exercise oscillatory ventilation (EOV) and is characterized by the periods of hyperpnea and hypopnea without interposed apnea. EOV is a non-invasive parameter detected during submaximal cardiopulmonary exercise testing. Presence of EOV during exercise in HF patients indicates significant impairment in resting and exercise hemodynamic parameters. EOV is also an independent risk factor for poor prognosis in HF patients both with reduced and preserved ejection fraction irrespective of other gas exchange variables. Circulatory delay, increased chemosensitivity, pulmonary congestion and increased ergoreflex signaling have been proposed as the mechanisms underlying the generation of EOV in HF patients. There is no proven treatment of EOV but its reversal has been noted with phosphodiesterase inhibitors, exercise training and acetazolamide in relatively small studies. In this review, we discuss the mechanistic basis of PB during exercise and the clinical implications of recognizing PB patterns in patients with HF. PMID:27022457

  10. Prognostic significance of modified Glasgow Prognostic Score in patients with non-metastatic clear cell renal cell carcinoma.

    PubMed

    Cho, Dae Sung; Kim, Sun Il; Choo, Seol Ho; Jang, Seok Heun; Ahn, Hyun Soo; Kim, Se Joong

    2016-06-01

    Objective The aim of this study was to evaluate the usefulness of the modified Glasgow Prognostic Score (mGPS) as a prognostic factor in patients with non-metastatic clear cell renal cell carcinoma (RCC). Materials and methods Between June 1994 and July 2012, 469 patients with RCC underwent radical or partial nephrectomy at two hospitals. Among these patients, 65 with non-clear cell type histology and 16 with lymph-node or distant metastasis were excluded. The medical records of the remaining 388 patients were retrospectively reviewed. The mGPS was calculated using a selective combination of C-reactive protein (CRP) and albumin as previously described. The prognostic significance of various clinicopathological variables including mGPS was analyzed using univariate and multivariate analyses. Results Of the total 388 patients, 40 patients (10.3%) developed local recurrence or distant metastasis and 18 patients (4.6%) died of disease during the follow-up period. The univariate analysis identified CRP, mGPS, thrombocytosis, T stage, Fuhrman's nuclear grade and lymphovascular invasion as significant prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS). The multivariate analysis indicated that mGPS (p < 0.001), T stage (p = 0.024) and lymphovascular invasion (p = 0.046) were independent prognostic factors for RFS, whereas mGPS (p = 0.001) was the only independent prognostic factor for CSS. Conclusions The mGPS is an independent prognostic factor for RFS and CSS in patients with non-metastatic clear cell RCC treated with radical or partial nephrectomy. These findings suggest that mGPS should be used for predicting recurrence or survival in patients undergoing nephrectomy for non-metastatic clear cell RCC. PMID:26878156

  11. Expression and prognostic significance of unique ULBPs in pancreatic cancer

    PubMed Central

    Chen, Jiong; Zhu, Xing-Xing; Xu, Hong; Fang, Heng-Zhong; Zhao, Jin-Qian

    2016-01-01

    Background Pancreatic cancer is one of the most lethal cancers worldwide, due to the lack of efficient therapy and difficulty in early diagnosis. ULBPs have been shown to behave as important protectors with prognostic significance in various cancers. Materials and methods Immunohistochemistry and enzyme-linked immunosorbent assays were used to explore the expression of ULBPs in cancer tissue and in serum, while survival analysis was used to evaluate the subsequent clinical value of ULBPs. Results Statistics showed that high expression of membrane ULBP1 was a good biomarker of overall survival (18 months vs 13 months), and a high level of soluble ULBP2 was deemed an independent poor indicator for both overall survival (P<0.001) and disease-free survival (P<0.001). Conclusion ULBP1 provides additional information for early diagnosis, and soluble ULBP2 can be used as a novel tumor marker to evaluate the risk of pancreatic cancer patients. PMID:27621649

  12. Prognostic significance of preoperative fibrinogen in patients with colon cancer

    PubMed Central

    Sun, Zhen-Qiang; Han, Xiao-Na; Wang, Hai-Jiang; Tang, Yong; Zhao, Ze-Liang; Qu, Yan-Li; Xu, Rui-Wei; Liu, Yan-Yan; Yu, Xian-Bo

    2014-01-01

    AIM: To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients. METHODS: A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1st 2005 to June 1st 2008 were enrolled in the study. All patients received radical surgery as their primary treatment method. Preoperative fibrinogen was detected by the Clauss method, and all patients were followed up after surgery. Preoperative fibrinogen measurements were correlated with a number of clinicopathological parameters using the Student t test and analysis of variance. Survival analyses were performed by the Kaplan-Meier method and Cox regression modeling to measure 5-year disease-free survival (DFS) and overall survival (OS). RESULTS: The mean preoperative fibrinogen concentration of all colon cancer patients was 3.17 ± 0.88 g/L. Statistically significant differences were found between preoperative fibrinogen levels and the clinicopathological parameters of age, smoking status, tumor size, tumor location, tumor-node-metastasis (TNM) stage, modified Glasgow prognostic scores (mGPS), white blood cell (WBC) count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and carcinoembryonic antigen (CEA) levels. Univariate survival analysis showed that TNM stage, tumor cell differentiation grade, vascular invasion, mGPS score, preoperative fibrinogen, WBC, NLR, PLR and CEA all correlated with both OS and DFS. Alpha-fetoprotein (AFP) and body mass index correlated only with OS. Kaplan-Meier analysis revealed that both OS and DFS of the total cohort, as well as of the stage II and III patients, were higher in the hypofibrinogen group compared to the hyperfibrinogen group (all P < 0.05). In contrast, there was no significant difference between OS and DFS in stage I patients with low or high fibrinogen levels. Cox regression analysis indicated preoperative fibrinogen levels, TNM stage, mGPS score, CEA, and

  13. Prognostic Significance of Signet Ring Gastric Cancer

    PubMed Central

    Taghavi, Sharven; Jayarajan, Senthil N.; Davey, Adam; Willis, Alliric I.

    2012-01-01

    Purpose Studies in Asia have questioned the dictum that signet ring cell carcinoma (SRC) has a worse prognosis than other forms of gastric cancer. Our study determined differences in presentation and outcomes between SRC and gastric adenocarcinoma (AC) in the United States. Patients and Methods The National Cancer Institute Surveillance, Epidemiology, and End Results database was reviewed for SRC and AC from 2004 to 2007. Results We reviewed 10,246 cases of patients with gastric cancer, including 2,666 of SRC and 7,580 of AC. SRC presented in younger patients (61.9 v 68.7 years; P < .001) and less often in men (52.7% v 68.7%; P < .001). SRC patients were more frequently black (11.3% v 10.9%), Asian (16.4% v 13.2%), American Indian/Alaska Native (0.9% v 0.8%), or Hispanic (23.3% v 14.0%; P < .001). SRC was more likely to be stage T3-4 (45.8% v 33.3%), have lymph node spread (59.7% v 51.8%), and distant metastases (40.2% v 37.6%; P < .001). SRC was more likely to be found in the lower (30.7% v 24.2%) and middle stomach (30.6% v 20.7%; P < .001). Median survival was not different between the two (AC, 14.0 months v SRC, 13.0 months; P = .073). Multivariable analyses demonstrated SRC was not associated with mortality (hazard ratio [HR], 1.05; 95% CI, 0.96 to 1.11; P = .150). Mortality was associated with age (HR, 1.01; 95% CI, 1.01 to 1.02; P < .001), black race (HR, 1.10; 95% CI, 1.01 to 1.20; P = .026), and tumor grade. Variables associated with lower mortality risk included Asian race (HR, 0.83; 95% CI, 0.77 to 0.91; P < .001) and surgery (HR, 0.37; 95% CI, 0.34 to 0.39; P < .001). Conclusion In the United States, SRC significantly differs from AC in extent of disease at presentation. However, when adjusted for stage, SRC does not portend a worse prognosis. PMID:22927530

  14. Prognostic significance of TP53 alterations in breast carcinoma.

    PubMed Central

    Andersen, T. I.; Holm, R.; Nesland, J. M.; Heimdal, K. R.; Ottestad, L.; Børresen, A. L.

    1993-01-01

    Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions. Immunohistochemistry demonstrated nuclear accumulation of p53 protein in 35 of 162 primary tumours (22%) and in four of 15 metastases (27%). TP53 mutation was strongly associated with nuclear accumulation of p53 protein. In total 42 of 163 primary tumours (26%) and 5 of 16 metastases (31%) were demonstrated to contain TP53 alterations (mutation and/or nuclear protein accumulation). TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival. Images Figure 1 Figure 2 PMID:8102535

  15. Prognostic significance of minichromosome maintenance proteins in breast cancer

    PubMed Central

    Kwok, Hang Fai; Zhang, Shu-Dong; McCrudden, Cian M; Yuen, Hiu-Fung; Ting, Kam-Po; Wen, Qing; Khoo, Ui-Soon; Chan, Kelvin Yuen-Kwong

    2015-01-01

    A role for the minichromosome maintenance (MCM) proteins in cancer initiation and progression is slowly emerging. Functioning as a complex to ensure a single chromosomal replication per cell cycle, the six family members have been implicated in several neoplastic disease states, including breast cancer. Our study aim to investigate the prognostic significance of these proteins in breast cancer. We studied the expression of MCMs in various datasets and the associations of the expression with clinicopathological parameters. When considered alone, high level MCM4 overexpression was only weakly associated with shorter survival in the combined breast cancer patient cohort (n = 1441, Hazard Ratio = 1.31; 95% Confidence Interval = 1.11-1.55; p = 0.001). On the other hand, when we studied all six components of the MCM complex, we found that overexpression of all MCMs was strongly associated with shorter survival in the same cohort (n = 1441, Hazard Ratio = 1.75; 95% Confidence Interval = 1.31-2.34; p < 0.001), suggesting these MCM proteins may cooperate to promote breast cancer progression. Indeed, their expressions were significantly correlated with each other in these cohorts. In addition, we found that increasing number of overexpressed MCMs was associated with negative ER status as well as treatment response. Together, our findings are reproducible in seven independent breast cancer cohorts, with 1441 patients, and suggest that MCM profiling could potentially be used to predict response to treatment and prognosis in breast cancer patients. PMID:25628920

  16. Prognostic Significance of Vascular Endothelial Growth Factor Serum Determination in Women with Ovarian Cancer

    PubMed Central

    Bandiera, Elisabetta; Franceschini, Roberta; Specchia, Claudia; Bignotti, Eliana; Trevisiol, Chiara; Gion, Massimo; Pecorelli, Sergio; Santin, Alessandro Davide; Ravaggi, Antonella

    2012-01-01

    Introduction. We performed a review of the literature to elucidate the potential prognostic significance of serum vascular endothelial growth factor (sVEGF) levels in ovarian cancer. Methods. Eligible studies in English and Italian were identified in MEDLINE/PubMed from VEGF discovery to October 2011. All studies evaluating: (i) sVEGF levels before any surgical and chemotherapeutic treatment; (ii) the association between sVEGF levels and the established prognostic variables; (iii) the value of sVEGF levels in predicting patients' outcomes, were selected for this review. Results. The search resulted in 758 titles. Nine studies met the inclusion criteria. A statistically significant association between the level of sVEGF and FIGO stage, tumour grade, residual tumour size, lymph node involvement, and presence of ascites was found in at least one study. sVEGF, in comparison with the established prognostic factors, appears to be the best prognostic marker for overall survival, since it stands out as an independent prognostic factor in most of the studies considered. Moreover, sVEGF levels were shown to be independent prognostic factors by 2 out of the 3 studies that considered DFS as an end point. Conclusion. High levels of sVEGF identify a subgroup of patients with higher risk of death and/or recurrence. These patients should be eligible for individually tailored therapeutic interventions. PMID:22792477

  17. Prognostic significance of angiogenesis in human pancreatic cancer

    PubMed Central

    Ikeda, N; Adachi, M; Taki, T; Huang, C; Hashida, H; Takabayashi, A; Sho, M; Nakajima, Y; Kanehiro, H; Hisanaga, M; Nakano, H; Miyake, M

    1999-01-01

    To evaluate whether angiogenic factors are of clinical relevance to actual human pancreatic cancers, we studied the intratumoral microvessel density (IMD), and PD-ECGF, VEGF protein expression in 40 pancreatic cancers using immunohistochemistry. We also investigated PD-ECGF and VEGF gene expression using reverse transcriptase-PCR (RT-PCR). Of the 40 pancreatic cancers studied, 30 carcinomas (75.0%) were evaluated to be PD-ECGF-positive and 10 carcinomas (25.0%) were determined to be PD-ECGF-negative. In contrast, 27 carcinomas (67.5%) were evaluated to be VEGF-positive, whereas 13 carcinomas (32.5%) were VEGF-negative. VEGF gene expression was moderately associated with an increase in the IMD (r2 = 0.181, P = 0.006), but no significant relationship was found between PD-ECGF gene expression and the IMD (r2 = 0.093, P = 0.059). However, tumours with positive expression for both PD-ECGF and VEGF had a higher IMD (P = 0.027). The results of the immunohistochemistry agreed well with the results of the quantitative RT-PCR. The median survival time of the hypervascular group was significantly shorter than that of the hypovascular group (P < 0.0001). In comparing the survival according to PD-ECGF and VEGF gene expression, the median survival time of the patients with positive PD-ECGF expression was significantly shorter than those with negative PD-ECGF expression (P = 0.040). Furthermore, the median survival time of the patients with positive VEGF expression was significantly shorter than those with negative VEGF expression (P = 0.048). However, the Cox multivariate analysis indicated that the IMD and VEGF expression were independent prognostic factors of the various clinicopathologic variables in pancreatic cancer patients (P = 0.0021 and P = 0.0443, respectively). © 1999 Cancer Research Campaign PMID:10188906

  18. Procalcitonin kinetics – prognostic and diagnostic significance in septic patients

    PubMed Central

    Mierzchała-Pasierb, Magdalena; Durek, Grażyna

    2016-01-01

    Introduction Severe sepsis and septic shock are advanced clinical conditions representing the patient's response to infection and having a variable but high mortality rate. Early evaluation of sepsis stage and choice of adequate treatment are key factors for survival. Some study results suggest the necessity of daily procalcitonin (PCT) monitoring because of its prognostic and discriminative value. Material and methods An observational and prospective study was conducted to evaluate the prognostic and discriminative value of PCT kinetics in comparison to PCT absolute value measurements. In a group of 50 intensive care unit patients with diagnosis of severe sepsis or septic shock, serum PCT measurements were performed on admission, and on the 2nd, 3rd and 5th day of therapy. The level of PCT was determined with a commercially available test according to the manufacturer's protocol. Results The kinetics of PCT assessed by ΔPCT was statistically significant in the survivors vs. the non-survivors subgroup (ΔPCT3/1, p = 0.022; ΔPCT5/1, p = 0.021). ΔPCT has no statistical significance in the severe sepsis and septic shock subgroups for all analyzed days. Only the 5th day PCT level was significantly higher in the non-survivors vs. survivors group (p = 0.008). The 1st day PCT level in the severe sepsis vs. septic shock group has a discriminative impact (p = 0.009). Conclusions According to the results, single serum PCT measurement, regardless of absolute value, has a discriminative impact but no prognostic significance, during the first 2 days of therapy. The PCT kinetics is of prognostic value from the 3rd day and is of earlier prognostic significance in comparison to changes in the patient's clinical condition evaluated by SOFA score kinetics. PMID:26925126

  19. Prognostic significance of hematological profiles in melanoma patients.

    PubMed

    Gandini, Sara; Ferrucci, Pier Francesco; Botteri, Edoardo; Tosti, Giulio; Barberis, Massimo; Pala, Laura; Battaglia, Angelo; Clerici, Alessandra; Spadola, Giuseppe; Cocorocchio, Emilia; Martinoli, Chiara

    2016-10-01

    Cancer-related inflammation may play an important role in disease progression and patient outcome, and could be easily monitored through indirect parameters routinely evaluated at diagnosis. Here, we investigated if peripheral blood cells and the ratios of neutrophils to lymphocytes (NLR) and of lymphocytes to monocytes (LMR) as surrogate markers of cancer related inflammation are associated with disease progression and survival of melanoma patients at any stage of the disease. Records of 1,182 melanoma patients included in an Institutional tumor registry in the period 2000-2010, were reviewed. Among them, 584 patients with a cutaneous or unknown primary melanoma and available pre-operative blood tests were analyzed. Survival was estimated with the Kaplan-Meier method, and analyzed using Log-rank test, Cox regression and multivariate Cox proportional hazard models. We found that patients presenting with distant metastases had higher leukocytes, neutrophils and monocytes, and lower lymphocytes compared to Stage I-III patients. Furthermore, at a single-patient level, hematological profiles changed on disease progression from regional to distant metastatic, with significantly increased circulating leukocytes, neutrophils and monocytes, and decreased lymphocytes. Peripheral blood cell counts were not associated with survival of patients with a localized or regionally metastasized melanoma. Instead, in Stage IV patients, leukocytes (p = 0.001), neutrophils (p = 0.0002), monocytes (p = 0.002), NLR (p < 0.0001) and LMR (p = 0.005) were all significantly associated with survival, independently of other known prognostic factors. These results suggest that cellular components of peripheral blood do count for survival of patients with advanced melanoma. PMID:27252119

  20. MIB-1 labelling index is an independent prognostic marker in primary breast cancer.

    PubMed Central

    Jansen, R. L.; Hupperets, P. S.; Arends, J. W.; Joosten-Achjanie, S. R.; Volovics, A.; Schouten, H. C.; Hillen, H. F.

    1998-01-01

    The proliferative activity of a tumour is considered to be an important prognostic factor in primary breast cancer. We have investigated the prognostic value of the MIB-1 labelling index in 341 patients with primary breast cancer and compared the results with the S-phase fraction in 220 patients of the same cohort. All patients were treated in one hospital and had a median follow-up of 128 months. No correlation between MIB-1 labelling and S-phase fraction could be demonstrated. MIB-1 had prognostic value for disease-free survival in the whole group of patients (P < 0.001) and in the node-negative subgroup (P < 0.001). In multivariate analysis, MIB-1 was an independent prognostic factor (P = 0.004) besides axillary lymph node status (P = 0.001). In univariate analysis high S-phase fraction was associated with decreased overall survival (P = 0.04); however, not in multivariate analysis. Moreover, S-phase fraction had a borderline prognostic significance for post-relapse survival in multivariate analysis (P= 0.08). Thus, in conclusion, the growth fraction of a tumour as determined by the MIB-1 labelling index is an important prognostic factor in patients with primary breast cancer. PMID:9716027

  1. Prognostic significance of NQO1 expression in intrahepatic cholangiocarcinoma

    PubMed Central

    Wakai, Toshifumi; Shirai, Yoshio; Sakata, Jun; Matsuda, Yasunobu; Korit, Pavel V; Takamura, Masaaki; Ajioka, Yoichi; Hatakeyama, Katsuyoshi

    2011-01-01

    This study aimed to evaluate the association between the immunohistochemical expression of NAD(P) H:quinone oxidoreductase-1 (NQO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in resected specimens of intrahepatic cholangiocarcinoma (ICC) and to elucidate the prognostic value of NQO1 and Nrf2 expression. A retrospective analysis was conducted of 34 consecutive patients who underwent surgical resection for ICC. Immunohistochemistry of the resected specimens was conducted using each of the following primary monoclonal antibodies against NQO1 and Nrf2. Of the 34 patients, 23 were classified as having tumors with NQO1-positive expression and 11 had tumors with loss of NQO1 expression, whereas 22 patients had tumors with Nrf2-positive expression and 12 had tumors with loss of Nrf2 expression. NQO1 expression showed a positive association with Nrf2 expression (p=0.005). Loss of NQO1 expression was more frequent in tumor specimens that were moderately or poorly differentiated (11/26; 42%) than in well-differentiated tumors (0/8; 0%; p=0.034). Post-resection survival was significantly worse in patients with tumors with loss of NQO1 expression than in patients with NQO1-positive tumors (cumulative 5 -year survival rate of 0% and 51%, respectively; p=0.005). Nrf2 expression was not associated with survival after resection (p=0.287). The Cox proportional hazards regression analysis revealed that lymph node involvement (p<0.001) and loss of NQO1 expression (p<0.001) had an independent adverse effect on survival. Loss of NQO1 expression reflects dedifferentiation and thus indicates a poor prognosis for patients undergoing resection for ICC. PMID:21577322

  2. Bile duct invasion can be an independent prognostic factor in early stage hepatocellular carcinoma

    PubMed Central

    Jang, Ye-Rang; Kim, Hyeyoung; Lee, Jeong-Moo; Yi, Nam-Joon; Suh, Kyung-Suk

    2015-01-01

    Backgrounds/Aims In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. Methods We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. Results Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. Conclusions Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2). PMID:26693236

  3. CCL21 as an independent favorable prognostic factor for stage III/IV colorectal cancer.

    PubMed

    Zou, Yifeng; Chen, Yufeng; Wu, Xianrui; Yuan, Ruixue; Cai, Zerong; He, Xiaosheng; Fan, Xinjuan; Wang, Lei; Wu, Xiaojian; Lan, Ping

    2013-08-01

    The aim of the present study was to investigate the expression dynamics of CCL21 and its prognostic significance in human stage III/IV colorectal cancer (CRC). CCL21 expression dynamics were detected with western blotting. The expression of CCL21 in CRC tissue microarrays was examined by immunohistochemistry. The optimal cut-point of CCL21 expression was assessed by the X-tile program. The prognostic significance was analyzed using both Kaplan-Meier curves and Cox regression analysis. Western blot analysis demonstrated that CCL21 expression was comparable in the CRC and normal colorectal tissues. According to the X-tile program, the cut-point for high expression of CCL21 in CRC was determined when the CCL21 expression index was >56.1. Overexpression of CCL21 was significantly correlated with larger tumor diameter, more mucinous carcinoma or signet ring cell carcinoma and poor tumor differentiation. Patients with high expression of CCL21 had a higher overall survival rate in comparison to patients with low expression. In the multivariate Cox regression analysis, CCL21 expression was found to be an independent prognostic biomarker for CRC. ROC curves showed that CCL21 expression could improve the prognostic capability of TNM stage in stage III/IV CRC patients. High expression of CCL21 is an independent and useful biomarker for predicting longer survival of stage III/IV CRC patients. PMID:23760102

  4. CD69 is independently prognostic in chronic lymphocytic leukemia: a comprehensive clinical and biological profiling study

    PubMed Central

    Del Poeta, Giovanni; Del Principe, Maria Ilaria; Zucchetto, Antonella; Luciano, Fabrizio; Buccisano, Francesco; Maria Rossi, Francesca; Bruno, Antonio; Biagi, Annalisa; Bulian, Pietro; Maurillo, Luca; Neri, Benedetta; Bomben, Riccardo; Simotti, Cristina; Coletta, Angela Maria; Dal Bo, Michele; de Fabritiis, Paolo; Venditti, Adriano; Gattei, Valter; Amadori, Sergio

    2012-01-01

    Background CD69 is expressed in several hemopoietic cells and is an early activation marker in chronic lymphocytic leukemia. Chronic lymphocytic leukemia is a clinically heterogeneous disease which needs novel prognostic parameters which can be easily and efficiently managed. Design and Methods We investigated CD69 by flow cytometry in a series of 417 patients affected by chronic lymphocytic leukemia and compared this to other biological and clinical prognosticators. Results CD69 was associated with Rai stages (P=0.00002), β2-microglobulin (P=0.0005) and soluble CD23 (P<0.0001). CD69 and ZAP-70 (P=0.018) or CD38 (P=0.00015) or immunoglobulin variable heavy chain gene mutations (P=0.0005) were also significantly correlated. Clinically, CD69 positive chronic lymphocytic leukemias received chemotherapy more frequently (74%; P<0.0001), and presented a shorter duration of response after fludarabine plus rituximab (P=0.010) as well as shorter progression free survival and overall survival (P<0.0001). CD69 demonstrated true additive prognostic properties, since the CD69+ plus ZAP-70+ or CD38+ or immunoglobulin variable heavy chain gene unmutated patients had the worst progression free survival and overall survival (P<0.0001). Interestingly, low CD69 expression was necessary to correctly prognosticate the longer progression free survival of patients with a low tumor burden of β2-microglobulin (P=0.002), of soluble CD23 (P=0.020), or of Rai stages 0-I (P=0.005). CD69 was confirmed to be an independent prognostic factor in multivariate analysis of progression free survival (P=0.017) and overall survival (P=0.039). Conclusions Our data indicate that CD69 is significantly correlated with poor clinical and biological prognostic factors and is confirmed to be an independent disease prognosticator. This supports its introduction in a routine laboratory assessment and, possibly, in a prognostic scoring system for chronic lymphocytic leukemia, after an adequate standardization

  5. Prognostic Significance of Ascites and Serum Sodium in Patients with Low Meld Scores

    PubMed Central

    Prohic, Dzanela; Mesihovic, Rusmir; Vanis, Nenad; Puhalovic, Amra

    2016-01-01

    Objective: to determine ascites and serum sodium significance in short term mortality prediction in patients with advanced liver cirrhosis. Methods: a cohort of 115 cirrhotic patients referred to our Department were followed up for 6 months in non-transplant settings. The c index equivalent to the area under the receiver operating curve (ROC) was calculated and compared to estimate the short-term prognostic accuracy of the following parameters: ascites, serum sodium and MELD score. Results: in patients with a MELD score less than 21, ascites and low serum sodium (c index 0,687, p<0 0,001 and 0,748, p<0,001 respectively) showed better prognostic accuracy and were independent predictors of mortality. For MELD scores above 21, only MELD was an independent mortality prognostic factor (c index 0,710, p<0,001). Conclusion: in our study, sample ascites and low serum sodium help identify patients with advanced liver disease who are at high risk of mortality despite low MELD scores. These parameters should be considered as additional prognostic parameters that could improve available treatment options and outcomes in this group of patients. PMID:26980932

  6. Survival kinase genes present prognostic significance in glioblastoma

    PubMed Central

    Varghese, Robin T.; Liang, Yanping; Guan, Ting; Franck, Christopher T.; Kelly, Deborah F.; Sheng, Zhi

    2016-01-01

    Cancer biomarkers with a strong predictive power for diagnosis/prognosis and a potential to be therapeutic targets have not yet been fully established. Here we employed a loss-of-function screen in glioblastoma (GBM), an infiltrative brain tumor with a dismal prognosis, and identified 20 survival kinase genes (SKGs). Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that the expression of CDCP1, CDKL5, CSNK1E, IRAK3, LATS2, PRKAA1, STK3, TBRG4, and ULK4 stratified GBM prognosis with or without temozolomide (TMZ) treatment as a covariate. For the first time, we found that GBM patients with a high level of NEK9 and PIK3CB had a greater chance of having recurrent tumors. The expression of CDCP1, IGF2R, IRAK3, LATS2, PIK3CB, ULK4, or VRK1 in primary GBM tumors was associated with recurrence-related prognosis. Notably, the level of PIK3CB in recurrent tumors was much higher than that in newly diagnosed ones. Congruent with these results, genes in the PI3K/AKT pathway showed a significantly strong correlation with recurrence rate, further highlighting the pivotal role of PIK3CB in the disease progression. Importantly, 17 SKGs together presented a novel GBM prognostic signature. SKGs identified herein are associated with recurrence rate and present prognostic significance in GBM, thereby becoming attractive therapeutic targets. PMID:26956052

  7. Survival kinase genes present prognostic significance in glioblastoma.

    PubMed

    Varghese, Robin T; Liang, Yanping; Guan, Ting; Franck, Christopher T; Kelly, Deborah F; Sheng, Zhi

    2016-04-12

    Cancer biomarkers with a strong predictive power for diagnosis/prognosis and a potential to be therapeutic targets have not yet been fully established. Here we employed a loss-of-function screen in glioblastoma (GBM), an infiltrative brain tumor with a dismal prognosis, and identified 20 survival kinase genes (SKGs). Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that the expression of CDCP1, CDKL5, CSNK1E, IRAK3, LATS2, PRKAA1, STK3, TBRG4, and ULK4 stratified GBM prognosis with or without temozolomide (TMZ) treatment as a covariate. For the first time, we found that GBM patients with a high level of NEK9 and PIK3CB had a greater chance of having recurrent tumors. The expression of CDCP1, IGF2R, IRAK3, LATS2, PIK3CB, ULK4, or VRK1 in primary GBM tumors was associated with recurrence-related prognosis. Notably, the level of PIK3CB in recurrent tumors was much higher than that in newly diagnosed ones. Congruent with these results, genes in the PI3K/AKT pathway showed a significantly strong correlation with recurrence rate, further highlighting the pivotal role of PIK3CB in the disease progression. Importantly, 17 SKGs together presented a novel GBM prognostic signature. SKGs identified herein are associated with recurrence rate and present prognostic significance in GBM, thereby becoming attractive therapeutic targets. PMID:26956052

  8. Prognostic significance of INF-induced transmembrane protein 1 in colorectal cancer

    PubMed Central

    He, Jingdong; Li, Jin; Feng, Wanting; Chen, Longbang; Yang, Kangqun

    2015-01-01

    Interferon-induced transmembrane protein 1 (IFITM1) has recently been implicated in tumorigenesis. However, the prognostic value of IFITM1 in colorectal cancer remains unknown. The present study aimed to examine the expression and prognostic significance of IFITM1 in human colorectal cancer. IFITM1 expression was analyzed in 144 archived, paraffin-embedded colorectal cancer tissues and corresponding normal colorectal mucosa by immunohistochemistry. The correlation of IFITM1 with clinic-pathological features and overall survival of colorectal cancer patients was evaluated. IFITM1 was overexpressed in colonic cancer tissues but not in rectal cancer tissues, compared to control normal tissues. The expression of IFITM1 was significantly higher in patients with poor differentiation (P=0.031). The patients with higher IFITM1 expression had worse overall survival outcomes than those with lower IFITM1 expression in rectal cancer (P=0.037). Univariate Cox regression suggested that older age and poorly differentiation status predict shorter overall survival in colorectal cancer (P<0.05). However, IFITM1 expression was not a significant prognostic factor for survival by univariate or multivariate analyses. In conclusion, high expression of IFITM1 is associated with poor prognosis of rectal cancer. IFITM1 may serve as an independent prognostic biomarker for colorectal cancer. PMID:26884876

  9. Increased Expression of PHGDH and Prognostic Significance in Colorectal Cancer.

    PubMed

    Jia, Xiao-Qin; Zhang, Shu; Zhu, Hui-Jun; Wang, Wei; Zhu, Jin-Hong; Wang, Xu-Dong; Qiang, Jian-Feng

    2016-06-01

    Phosphoglycerate dehydrogenase (PHGDH) plays an essential role in cancer-specific metabolic reprogramming. It has been reported as a putative metabolic oncogene in several types of human malignant tumors, such as breast cancer and melanoma. To date, PHGDH expression in colorectal cancer (CRC) as well as its association with clinicopathological characteristics and prognostic implication remain undetermined. In this study, we determined the PHGDH protein expression using tissue microarray immunohistochemistry (TMA-IHC) on 193 pairs of formalin-fixed, paraffin-embedded specimens of CRC and adjacent tissues, 25 chronic colitis, 41 low-, and 19 high-grade intraepithelial neoplasia specimens, and we also determined PHGDH mRNA level using quantitative reverse transcription PCR (qRT-PCR) on additional 23 pairs of fresh CRC tissues and adjacent tissues. We found that both PHGDH mRNA and protein was highly expressed in tumor tissues in comparison with matched adjacent non-tumor tissues, and high PHGDH protein expression was correlated with advanced TNM stage (P = .038) and larger tumor (P = .001). Multivariate Cox regression analysis showed that PHGDH protein expression (HR = 2.285, 95% CI = 1.18 to 4.41, P = .014), tumor differentiation (HR = .307, 95% CI = .154 to 0.609, P = .001), and TNM stage (HR = 1.791, 95% CI = 1.125 to 2.85, P = .014) were independent prognostic factors in CRC. Kaplan-Meier survival curves and log rank test showed that high PHGDH protein expression contributed to poor outcome in CRC patients (P < .001). In conclusion, these results suggest that assessment of PHGDH expression could be useful in identifying a high-risk subgroup of CRC. PMID:27267836

  10. Expression and prognostic significance of apolipoprotein D in breast cancer.

    PubMed Central

    Díez-Itza, I.; Vizoso, F.; Merino, A. M.; Sánchez, L. M.; Tolivia, J.; Fernández, J.; Ruibal, A.; López-Otín, C.

    1994-01-01

    Apolipoprotein D (apo D) is a glycoprotein involved in the human plasma lipid transport system and present at large amounts in cyst fluid from women with gross cystic disease of the breast. Apo D expression in breast carcinomas was examined by immunoperoxidase staining of a series of 163 tumors. A total of 60 (36.8%) tumors were negative for apo D immunostaining, 28 (17.2%) carcinomas were weakly positive, 33 (20.2%) were moderately stained, whereas the remaining 42 (25.8%) tumors were strongly stained with the specific antibodies. No significant correlation was found between apo D content and tumor size, lymph node involvement, or biochemical parameters such as estrogen receptors, cathepsin D, or pS2 protein. However, the finding of a significant association between apo D and menopausal status of patients or differentiation grade of tumors, with apo D values being lower in tumors from premenopausal women or in poorly differentiated carcinomas, suggested a potential value of this glycoprotein as a prognostic factor in breast cancer. Preliminary analysis of relapse-free survival and overall survival in a subgroup of 152 women with a mean follow-up of 42 months confirmed that low apo D values were significantly associated to a shorter relapse-free survival and poorer survival. According to these data, we propose that apo D in combination with other well-established prognostic factors may contribute to more accurately identify subgroups of breast cancer patients with low or high risk for relapse and death. Images Figure 1 Figure 2 Figure 3 PMID:8311115

  11. Prognostic significance of CT-emphysema score in patients with advanced squamous cell lung cancer

    PubMed Central

    Kim, Young Saing; Ahn, Hee Kyung; Cho, Eun Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Although emphysema is a known independent risk factor of lung cancer, no study has addressed the prognostic impact of computed tomography (CT)-emphysema score in advanced stage lung cancer. Methods For 84 consecutive patients with stage IIIB and IV squamous cell lung cancer that underwent palliative chemotherapy, severity of emphysema was semi-quantitatively scored using baseline chest CT images according to the Goddard scoring system (possible scores range, 0–24). The cutoff of high CT-emphysema score was determined using the maximum chi-squared test and the prognostic significance of the high CT-emphysema score was evaluated using Kaplan-Meier analysis and Cox proportional hazards analysis. Results The median CT-emphysema score was 5 (range, 0–22). Patients with a high CT-emphysema score (≥4) tended to have poorer overall survival (OS) (median: 6.3 vs. 13.7 months) than those with a score of <4 (P=0.071). Multivariable analysis revealed that a higher CT-emphysema score was a significant independent prognostic factor for poor OS [hazard ratio (HR) =2.06; 95% confidence interval (CI), 1.24–3.41; P=0.005), along with no response to first-line therapy (P=0.009) and no second-line therapy (P<0.001). Conclusions CT-emphysema score is significantly associated with poor prognosis in patients with advanced squamous cell lung cancer.

  12. CA9 overexpression is an independent favorable prognostic marker in intrahepatic cholangiocarcinoma

    PubMed Central

    Gu, Mijin

    2015-01-01

    The aim of this study is to evaluate the expression of carbonic anhydrase IX (CA9) and to identify its prognostic significance in intrahepatic cholangiocarcinoma (IHCC). We performed immunohistochemistry (IHC) for CA9 in a total of 85 IHCCs. CA9 overexpression was observed in 38 of 85 (44.7%) IHCCs. CA9 overexpression was related to tumors with intraductal growth than mass forming or periductal infiltrative type. CA9 overexpression was more observed in tumors with well/moderate differentiation than poor differentiation and without lymph node metastasis. No significant correlation was observed in CA9 overexpression with tumor size, pT, stage and lymphovascular invasion. Intrahepatic cholangiocarcinomas with CA9 overexpression showed better overall survival than that without expression (P = 0.001). In multivariate analysis, lymph node metastasis (95% CI: 2.103 (1.167-3.791), P = 0.013) was an independent poor prognostic factor. IHCC with CA9 overexpression showed a 0.5-fold (95% confidence interval, 0.328-0.944) lower risk of death compared with those of no or weak expression. CA9 overexpression was related to histologic differentiation and an independent good prognostic factor. PMID:25755787

  13. The prognostic significance of altered cyclin-dependent kinase inhibitors in human cancer.

    PubMed

    Tsihlias, J; Kapusta, L; Slingerland, J

    1999-01-01

    Progression through the cell cycle is governed by cyclin-dependent kinases (cdks), whose activity is inhibited by the cdk inhibitors. Cyclins, cdks, and cdk inhibitors are frequently deregulated in cancers. This chapter reviews the prognostic significance of alterations in cdk inhibitors. Loss of p27 protein provides independent prognostic information in breast, prostate, colon, and gastric carcinomas, and immunohistochemical (IHC) staining for p27 may eventually become part of routine histopathologic processing of cancers. Loss of IHC staining for p21 may be prognostic in certain cancers but conflicting results are reported in breast cancer. Reports on homozygous deletion of p16 and p15 genes suggest the value of larger, prospective studies with standardized treatment protocols to definitively establish the prognostic utility of p15/p16 deletions in acute leukemias. Larger trials and the development of a consensus on methods for deletion analysis, IHC staining, and tumor scoring will be needed to move these molecular assays from bench to bedside. PMID:10073286

  14. Prognostic Significance of the Tumor-Stroma Ratio in Epithelial Ovarian Cancer

    PubMed Central

    Chen, Ying; Zhang, Lei; Liu, Wenxin; Liu, Xiangyu

    2015-01-01

    Tumor-stroma ratio (TSR) has recently been identified as a promising prognostic parameter for several solid tumors. This study aimed to evaluate the prognostic role of TSR in epithelial ovarian cancer (EOC) and 838 EOC patients were enrolled in this study. TSR was estimated on hematoxylin-and-eosin-stained tissue sections from the most invasive part of the primary tumor. Patients were classified as stroma-rich or stroma-poor according to the proportion of stroma ≥50% or <50%. Chi-square test analysis revealed that TSR were significantly associated with FIGO stage, LN status, and recurrence or not (all of them P < 0.001). The higher stroma-rich proportions were found in EOC patients with advanced stage (36.13% versus 19.75%), LN metastasis (51.93% versus 27.25%), and recurrence (34.27% versus 6.82%). Stroma-rich EOC patients had obvious shorter median time of progression-free survival (29 versus 39 months) and overall survival (50 versus 58 months), respectively. TSR was an independent prognostic factor for the evaluation of PFS in EOC. Stroma-rich tumors had worse prognosis and higher risk of relapse compared with those in stroma-poor tumors in EOC patients. Considered easy to determine for routine pathological examination, TSR may serve as a new prognostic histological parameter in EOC. PMID:26609529

  15. The prognostic significance of fibroblast growth factor receptor 4 in non-small-cell lung cancer

    PubMed Central

    Huang, Hong-ping; Feng, Hui; Qiao, Hong-bo; Ren, Ze-xiang; Zhu, Ge-dong

    2015-01-01

    Background Fibroblast growth factor receptor 4 (FGFR4) has been proved to be correlated with progression and prognosis in many cancers. However, the significance of FGFR4 in non-small-cell lung cancer (NSCLC) is still not well elucidated. Methods In our experiment, we detected FGFR4 expression in 237 samples of NSCLC with immunohistochemistry, and further analyzed the correlation between FGFR4 and clinicopathologic features of NSCLC with chi-square test. Moreover, we evaluated the prognostic value of FGFR4 by Kaplan–Meier survival curve and Cox regression model. By regulating the expression of FGFR4 by overexpression or knockdown, we assessed the role of FGFR4 on NSCLC cell proliferation. Results FGFR4 expression was high in NSCLC (46.8%, 111/237). FGFR4 expression was significantly associated with tumor diameter (P=0.039). With univariate (P=0.009) and multivariate (P=0.002) analysis, FGFR4 was identified as an independent prognostic factor in NSCLC (P=0.009). Moreover, FGFR4 can promote the proliferation of NSCLC cell lines. Conclusion FGFR4 is an independent prognostic biomarker in NSCLC. FGFR4 can accelerate the proliferation of NSCLC cell lines, indicating FGFR4 could be a potential drug target of NSCLC. PMID:26045670

  16. Prognostic and Biological Significance of MicroRNA-127 Expression in Human Breast Cancer

    PubMed Central

    Wang, Shaohua; Li, Hanjun; Wang, Jingjie; Wang, Dan; Yao, Anlong; Li, Qiurong

    2014-01-01

    The purpose of this study was to determine the expression of miR-127 and analyze its prognostic and biological significance in breast cancer (BC). A quantitative reverse transcription PCR assay was performed to detect the expression of miR-127 in 15 pairs of BC and corresponding noncancerous tissues. The expression of miR-127 was detected in another 110 BC tissues and its correlations with clinicopathological factors of patients were examined. Univariate and multivariate analyses were performed to analyze the prognostic significance of miR-127 expression. The effects of miR-127 expression on malignant phenotypes of BC cells and its possible molecular mechanisms were further determined. miR-127 was significantly downregulated in BC tissues, and low miR-127 expression was significantly correlated with lymph node metastasis and advanced clinical stage. Patients with low miR-127 showed poorer overall survival than those with high miR-127. Multivariate analyses indicated that status of miR-127 was an independent prognostic factor for patients. Functional analyses showed that upregulation of miR-127 significantly inhibited growth, enhanced apoptosis, and reduced migration and invasion in BC cells by targeting the protooncogene BCL-6. Therefore, miR-127 may be a potential biomarker for predicting the survival of BC patients and might be a molecular target for treatment of human BCs. PMID:25477702

  17. Chromatin CKAP2, a New Proliferation Marker, as Independent Prognostic Indicator in Breast Cancer

    PubMed Central

    Choi, Yong-Bock; Ro, Jungsil; Kim, Hyun-Kyoung; Kim, Mi-Kyung; Nam, Byung-Ho; Kim, Kyung-Tae; Chandra, Vishal; Seol, Hye-Sil; Noh, Woo-Chul; Kim, Eun-Kyu; Park, Joobae; Bae, Chang-Dae; Hong, Kyeong-Man

    2014-01-01

    Background The level of proliferation activity is a strong prognostic or predictive indicator in breast cancer, but its optimal measurement is still in debate, necessitating new proliferation markers. In the present study, the prognostic significance of the CKAP2-positive cell count (CPCC), a new proliferation marker, was evaluated, and the results were compared with those for the mitotic activity index (MAI). Methods This study included 375 early-stage breast cancer samples collected from two institutions between 2000 and 2006. Immunohistochemical staining was performed using a CKAP2 monoclonal antibody. Cox proportional hazard regression models were fitted to determine the association between the CPCC and relapse-free survival (RFS) amongst three groups formed on the basis of the CPCC or MAI value: groups 2 and 3 showing the middle and highest values, respectively, and group 1 the lowest. Results After adjustment for age, T stage, N stage, HER2 status, estrogen receptor status, progesterone receptor status, institution, and year of surgical resection, the CPCC was associated with a significantly worse RFS {hazard ratio [HR]  = 4.10 (95% CI: 1.64–10.29) for group 2; HR  = 4.35 (95% CI: 2.04–10.35) for group 3}. Moreover, its prognostic significance was similar to or higher than that based on the MAI {HR  = 2.05 (95% CI: 0.94–4.65) for group 2; HR  = 2.35 (95% CI: 1.09–5.10) for group 3}. In subgroup analyses, the CPCC showed a prognostic significance in the luminal A and triple-negative subgroups, but not in the HER2-positive subgroup. Conclusions Chromatin CKAP2 is an independent prognostic marker for RFS in early-stage breast cancer, and could potentially replace the MAI in clinical evaluation of proliferation activity. Additionally, our study results suggest that the prognostic significance of proliferation activity differs among the various subgroups of breast cancer. PMID:24887265

  18. Prognostic significance of urinary NGAL in chronic kidney disease

    PubMed Central

    Patel, Munna Lal; Sachan, Rekha; Misra, Ravi; Kamal, Ritul; Shyam, Radhey; Sachan, Pushpalata

    2015-01-01

    Background Chronic kidney disease (CKD) is a worldwide public health problem. Recently urinary NGAL (uNGAL) has been proven to be a useful (potentially ideal) biomarker for early detection of CKD. The aim of the present study was to examine the correlation of uNGAL with severity of renal impairment in CKD and to evaluate its prognostic value in these subjects. Methods This was a prospective study carried out over a period of 24 months in subjects with CKD due to primary chronic glomerulonephritis. New cases of CKD stage II, III, IV aged between 18 and 65 years were enrolled as per KDIGO (Kidney Disease: Improving Global Outcomes) guidelines 2012. A total of 90 subjects completed the study up to the end-point. The primary follow-up end-point was 18 months, or decreased glomerular filtration rate of less than 15 mL/min. Secondary follow-up end-point was the number of subjects who expired during this period. Results Multiple regression model of estimated glomerular filtration rate showed significant associations with log uNGAL (β=0.38, P<0.001), Ca×PO4 (β=0.60, P<0.001), hemoglobin (β=0.37, P<0.001), urine protein (β=0.34, P<0.001), serum albumin (β=0.48, P<0.001), and systolic blood pressure (β=0.76, P<0.001). Receiver operator curve for uNGAL considering the progression of CKD showed area under the curve for uNGAL was 0.878 (95% confidence interval: 0.68–0.96). Cut-off value for uNGAL was log 3.5 unit with a sensitivity of 93.08% and specificity of 71.43% for predicting the progression of CKD. Kaplan–Meier survival curve showed that patients with log uNGAL levels <3.51 unit had a survival rate of 71.4% while patients with NGAL level >3.51 unit had a renal survival rate of 14.7%. Conclusion Our study result showed that uNGAL has a positive correlation with disease severity which signifies the prognostic importance of uNGAL in CKD. PMID:26508883

  19. Hypoxia inducible BHLHB2 is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma

    SciTech Connect

    Wang, Weibin; Reiser-Erkan, Carolin; Michalski, Christoph W.; Raggi, Matthias C.; Quan, Liao; Yupei, Zhao; Friess, Helmut; Erkan, Mert; Kleeff, Joerg

    2010-10-22

    Research highlights: {yields} The expression and function of BHLHB2 (DEC1/SHARP2) in pancreatic cancer is unknown. {yields} Hypoxia and serum starvation induces BHLHB2 expression in pancreatic ductal adenocarcinoma. {yields} BHLHB2 inhibition in pancreatic cancer cell line SU86.86 increases ED50 of gemcitabine 2.8-fold. {yields} BHLHB2 is an independent prognostic factor in multivariable cox analysis with a hazard ratio of 2:4. -- Abstract: Aims: The cyclic adenosine monophosphate-inducible basic helix-loop-helix (bHLH) domain containing class-B2 transcriptional factor BHLHB2 is differentially expressed in a number of human malignancies. In the present study, the expression, regulation, functions and prognostic impact of BHLHB2 in pancreatic cancer were investigated. Methods: Expression analyses were carried out in tissues of the normal pancreas (n = 10) and pancreatic ductal adenocarcinoma (n = 77) as well as in eight pancreatic cancer cell lines using quantitative RT-PCR, semiquantitative immunohistochemistry, and immunoblot analyses. In vitro functional experiments were conducted using siRNA transfection, hypoxia, serum starvation, apoptosis induction with gemcitabine and actinomycin-D, and invasion assays. Survival analysis was performed using the Kaplan-Meier method. Prognostic factors were determined in a multivariable analysis using a Cox proportional hazards model. Results: BHLHB2 mRNA and protein expressions were strongly induced by hypoxia and by serum starvation in pancreatic cancer cell lines. BHLHB2 silencing with RNAi had no significant effects on growth and invasion but increased apoptosis resistance against gemcitabine by reducing caspace-3 cleavage. In BHLHB2 silenced cells the ED50 of gemcitabine increased from 13.95 {+-} 1.353 to 38.70 {+-} 5.262 nM (p < 0.05). Ex vivo, the weak/absent nuclear staining in normal pancreatic ducts and acinar cells was replaced by moderate to strong nuclear/cytoplasmic staining in PanIN lesions and pancreatic cancer

  20. Interleukin-33 in human gliomas: Expression and prognostic significance

    PubMed Central

    GRAMATZKI, DOROTHEE; FREI, KARL; CATHOMAS, GIERI; MOCH, HOLGER; WELLER, MICHAEL; MERTZ, KIRSTEN DIANA

    2016-01-01

    Interleukin-33 (IL-33) is a nuclear and pleiotropic cytokine with regard to its cellular sources and its actions. IL-33 is involved in the pathogenesis of brain diseases. Several factors account for the tumorigenicity of human gliomas, including cytokines and their receptors. The present study assessed the expression and prognostic significance of IL-33 in human astroglial brain tumors. Protein levels of IL-33 were determined by immunohistochemistry using a tissue microarray containing 95 human gliomas. mRNA expression data of IL-33, as well as of its receptors, IL-1 receptor-like 1 protein and IL-1 receptor accessory protein (IL1RAcP), were obtained from The Cancer Genome Atlas database. IL-33 protein was expressed heterogeneously in tumor tissue, but was, however, not detected in normal brain tissue. There was no differential IL-33 protein expression by tumor grade, while IL-33 protein expression was associated with inferior survival in patients with recurrent glioblastomas. Interrogations of the TCGA database indicated that mRNA expression of IL-33 and the IL-33 receptors was heterogeneous, and that IL-33 and IL1RAcP mRNA levels were correlated with the tumor grade. Elevated IL-33 mRNA levels were associated with the inferior survival of glioblastoma patients. Therefore, IL-33 may play an important role in the pathogenesis and prognosis of human gliomas. PMID:27347163

  1. Proliferative activity is a significant prognostic factor in male breast carcinoma.

    PubMed Central

    Pich, A.; Margaria, E.; Chiusa, L.

    1994-01-01

    The proliferative activity of male breast carcinoma has been investigated using the staining of the argyrophilic nucleolar organizer regions (AgNORs), the monoclonal antibody against the proliferating cell nuclear antigen (PC10) and the monoclonal antibody MIB-1 in formalin-fixed, paraffin-embedded specimens from 27 primary male breast carcinomas at diagnosis. A significant correlation was found between survival and AgNOR counts (median of survival 77 months for cases with AgNOR/cell < or = 7.27 but 37 months only for cases with > 7.27 AgNOR/cell; P = 0.001), proliferating cell nuclear antigen scores (median of survival 73 months for cases with proliferating cell nuclear antigen < or = 18.25% versus 41 for cases with proliferating cell nuclear antigen > 18.25%; P = 0.013) and MIB-1 scores (median of survival 73 months for cases with MIB-1 scores < or = 23.5% versus 37 months for cases with MIB-1 scores > 23.5%; P = 0.01). Tumor histological grade was also correlated with prognosis (median of survival 72 months for grade 2 versus 33 months for grade 3 tumors; P = 0.01). Estrogen and progesterone receptors, immunohistochemically detected on paraffin-embedded sections, had no prognostic value. In the multivariate survival analysis, only AgNOR counts (P = 0.007) and tumor size (P = 0.003) had an independent prognostic significance. Our results indicate that methods for assessing the cell proliferation in routinely processed specimens offer significant prognostic information in male breast carcinoma. The finding, together with the lack of prognostic significance for estrogen receptors and progesterone receptors, suggests that male breast carcinoma is biologically different from female breast cancer. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7519830

  2. High Myeloperoxidase Positive Cell Infiltration in Colorectal Cancer Is an Independent Favorable Prognostic Factor

    PubMed Central

    Eppenberger-Castori, Serenella; Zlobec, Inti; Viehl, Carsten T.; Frey, Daniel M.; Nebiker, Christian A.; Rosso, Raffaele; Zuber, Markus; Amicarella, Francesca; Iezzi, Giandomenica; Sconocchia, Giuseppe; Heberer, Michael; Lugli, Alessandro; Tornillo, Luigi; Oertli, Daniel

    2013-01-01

    Background Colorectal cancer (CRC) infiltration by adaptive immune system cells correlates with favorable prognosis. The role of the innate immune system is still debated. Here we addressed the prognostic impact of CRC infiltration by neutrophil granulocytes (NG). Methods A TMA including healthy mucosa and clinically annotated CRC specimens (n = 1491) was stained with MPO and CD15 specific antibodies. MPO+ and CD15+ positive immune cells were counted by three independent observers. Phenotypic profiles of CRC infiltrating MPO+ and CD15+ cells were validated by flow cytometry on cell suspensions derived from enzymatically digested surgical specimens. Survival analysis was performed by splitting randomized data in training and validation subsets. Results MPO+ and CD15+ cell infiltration were significantly correlated (p<0.0001; r = 0.76). However, only high density of MPO+ cell infiltration was associated with significantly improved survival in training (P = 0.038) and validation (P = 0.002) sets. In multivariate analysis including T and N stage, vascular invasion, tumor border configuration and microsatellite instability status, MPO+ cell infiltration proved an independent prognostic marker overall (P = 0.004; HR = 0.65; CI:±0.15) and in both training (P = 0.048) and validation (P = 0.036) sets. Flow-cytometry analysis of CRC cell suspensions derived from clinical specimens showed that while MPO+ cells were largely CD15+/CD66b+, sizeable percentages of CD15+ and CD66b+ cells were MPO−. Conclusions High density MPO+ cell infiltration is a novel independent favorable prognostic factor in CRC. PMID:23734221

  3. KIF23 is an independent prognostic biomarker in glioma, transcriptionally regulated by TCF-4.

    PubMed

    Sun, Lihua; Zhang, Chuanbao; Yang, Zhengxiang; Wu, Yiping; Wang, Hongjun; Bao, Zhaoshi; Jiang, Tao

    2016-04-26

    Kinesin family member 23 (KIF23), a nuclear protein and a key regulator of cellular cytokinesis, has been found to be overexpressed as an oncogene in glioma. However, the prognostic and clinicopathological features of glioma with KIF23 expression was not clear yet. Here, we analyzed KIF23 expression pattern by using whole genome mRNA expression microarray data from Chinese Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn), and found that KIF23 overexpression was significantly associated with high grade glioma as well as the higher mortality in survival analysis (log-rank test, p<0.01). The results of the three other validation datasets showed similar findings. Furthermore, KIF23 also served as an independent prognostic biomarker in glioma patients. Finally, functional assay showed that reduction of KIF23 suppressed glioma cell proliferation both in vivo and vitro. Additionally, we found that KIF23 was regulated by TCF-4 at transcriptionally level. Therefore, this evidence indicates KIF23 over-expression is associated with glioma malignancy and conferred a worse survival time in glioma, which suggests KIF23 is a new novel prognostic biomarker with potential therapeutic implications in glioma. PMID:27013586

  4. The prognostic significance of survivin expression in gallbladder carcinoma.

    PubMed

    Salman, Tarik; Argon, Asuman; Kebat, Tulu; Vardar, Enver; Erkan, Nazif; Alacacıoğlu, Ahmet

    2016-08-01

    Gallbladder cancers (GBC) are characterized by rapid progression, early metastasis, and poor prognosis; the molecular mechanisms of the various signaling pathways involved should be elucidated to develop effective therapies. Survivin, an apoptosis inhibitor protein expressed in the G2/M phase of the cell cycle, plays a role in cell division and affects both cell survival and proliferation. Survivin has been investigated in many types of cancer, and this study aims to examine the relationship of survivin expression in gallbladder cancer patients with clinicopathological features and prognosis. We evaluated demographic characteristics (age, gender), tumor characteristics (histopathological type, differentiation, perineural, and lymphovascular invasion; serosal invasion, surgical margin positivity and lymphocytic response), and Survivin expression immunohistochemically, and we analysed the relationship between these characteristics and prognosis in 47 gallbladder carcinoma cases from 2000 to 2011. Immunohistochemically, while survivin expression was observed in 36 cases, it was absent in 11 cases. Follow-up data were obtained from 32 patients. Two (8.7%) of 23 cases with a Survivin-positive tumor were alive at 74th and 35th months, whereas 5 (%55.6) of nine cases with Survivin-negative tumor were alive at 50th, 89th, 124th, 126th, 131th months. Survivin expression was correlated with short survival (p = 0.043), and the univariate analysis showed that reduced overall survival was associated with age (p = 0.043), male gender (p = 0.038), infiltrative pattern (p = 0.019), lymphovascular invasion (p = 0.004), perineural invasion (p = 0.009), serosal invasion (p = 0.027), ulcer (p = 0.033), and surgical margin positivity (p = 0.022). Despite the low number of patients in our study, the analysis results suggest that survivin positivity might actually be a significant prognostic factor. This finding could be a reference point for targeted treatment studies. However, further

  5. Intra-Gene DNA Methylation Variability Is a Clinically Independent Prognostic Marker in Women’s Cancers

    PubMed Central

    Bartlett, Thomas E.; Jones, Allison; Goode, Ellen L.; Fridley, Brooke L.; Cunningham, Julie M.; Berns, Els M. J. J.; Wik, Elisabeth; Salvesen, Helga B.; Davidson, Ben; Trope, Claes G.; Lambrechts, Sandrina; Vergote, Ignace; Widschwendter, Martin

    2015-01-01

    We introduce a novel per-gene measure of intra-gene DNA methylation variability (IGV) based on the Illumina Infinium HumanMethylation450 platform, which is prognostic independently of well-known predictors of clinical outcome. Using IGV, we derive a robust gene-panel prognostic signature for ovarian cancer (OC, n = 221), which validates in two independent data sets from Mayo Clinic (n = 198) and TCGA (n = 358), with significance of p = 0.004 in both sets. The OC prognostic signature gene-panel is comprised of four gene groups, which represent distinct biological processes. We show the IGV measurements of these gene groups are most likely a reflection of a mixture of intra-tumour heterogeneity and transcription factor (TF) binding/activity. IGV can be used to predict clinical outcome in patients individually, providing a surrogate read-out of hard-to-measure disease processes. PMID:26629914

  6. Prognostic significance of prospectively detected bone marrow micrometastases in esophagogastric cancer: 10-year follow-up confirms prognostic significance.

    PubMed

    Ryan, Paul; Furlong, Heidi; Murphy, Conleth G; O'Sullivan, Finbarr; Walsh, Thomas N; Shanahan, Fergus; O'Sullivan, Gerald C

    2015-08-01

    We have previously reported that most patients with esophagogastric cancer (EGC) undergoing potentially curative resections have bone marrow micrometastases (BMM). We present 10-year outcome data of patients with EGC whose rib marrow was examined for micrometastases and correlate the findings with treatment and conventional pathologic tumor staging. A total of 88 patients with localized esophagogastric tumors had radical en-bloc esophagectomy, with 47 patients receiving neoadjuvant (5-fluorouracil/cisplatin based) chemoradiotherapy (CRT) and the remainder being treated with surgery alone. Rib marrow was examined for cytokeratin-18-positive cells. Standard demographic and pathologic features were recorded and patients were followed for a mean 10.04 years. Disease recurrences and all deaths in the follow-up period were recorded. No patients were lost to follow-up. 46 EGC-related and 10 non-EGC-related deaths occurred. Multivariate Cox analysis of interaction of neoadjuvant chemotherapy, nodal status, and BMM positivity showed that the contribution of BMM to disease-specific and overall survival is significant (P = 0.014). There is significant interaction with neoadjvant CRT (P < 0.005), and lymph node positivity (P < 0.001) but BMM positivity contributes to increase in risk of cancer-related death in patients treated with either CRT or surgery alone. Bone marrow micrometastases detected at the time of surgery for EGC is a long-term prognostic marker. Detection is a readily available, technically noncomplex test which offers a window on the metastatic process and a refinement of pathologic staging and is worthy of routine consideration. PMID:25914238

  7. Prognostic significance of RelB overexpression in non‐small cell lung cancer patients

    PubMed Central

    Qin, Hualong; Zhou, Jun; Zhou, Peng; Xu, Jingjing; Tang, Zaixiang

    2016-01-01

    Background Lung cancer is a major public health issue in most countries, including China. The expression of RelB is associated with poor prognosis in diverse cancers. However, whether RelB expression could be an indicator of poor prognosis in non‐small cell lung cancer (NSCLC) is still unclear. Methods The expression of RelB in NSCLC tumor tissue and adjacent non‐neoplastic tissues were examined by immunohistochemistry. Chi‐square or two‐tailed Fisher's exact tests were used to analyze possible associations between qualitative clinicopathological variables and RelB expression. Kaplan–Meier analysis and a Cox regression model were employed to determine independent prognostic factors. Results The expression of RelB was increased in tumor tissue compared with adjacent non‐neoplastic tissue in NSCLC patients. High RelB expression was significantly correlated with degree of differentiation (P = 0.023), depth of tumor invasion (P < 0.001), lymph node metastasis (P = 0.017), distant metastases (P = 0.004), and tumor node metastasis stage (P < 0.001) in patients with NSCLC. NSCLC patients with high RelB expression had significantly shorter overall survival than those with low RelB expression (P < 0.001). Our results indicate that high RelB expression is an independent prognostic factor for patients with NSCLC (P < 0.001). Conclusions High RelB expression could provide a basis for judgment of prognosis in patients with NSCLC. PMID:27385983

  8. Clinical Significance of the Glasgow Prognostic Score for Survival after Colorectal Cancer Surgery.

    PubMed

    Eren, Tunc; Burcu, Busra; Tombalak, Ercument; Ozdemir, Tugrul; Leblebici, Metin; Ozemir, Ibrahim Ali; Ziyade, Sedat; Alimoglu, Orhan

    2016-06-01

    Glasgow prognostic score (GPS) has been found to be a useful tool in various cancer types. Our aim was to evaluate the significance of GPS in patients operated on for colorectal cancer (CRC). Patients with CRC who underwent radical resections between April 2010 and January 2015 were retrospectively evaluated. GPS was estimated based on the preoperative measurement of C-reactive protein and serum albumin levels. Data including demographics, laboratory and pathological parameters, surgical outcomes, and late-term follow-up results were analyzed. The study group of 115 patients consisted of 51 (44 %) women and 64 (56 %) men with a median age of 66 (range 32-91) years. The mean follow-up period was 20 (range 7-41) months. Tumor size and wound infection rates were significantly increased in patients with higher GPS (p = 0.019 and p = 0.003, respectively). According to multivariate analyses, CEA and GPS were found to be independent risk factors significantly effecting mortality (p = 0.001 and p = 0.009, respectively). At the end of the late-term follow-up period, it was detected that cancer-specific survival significantly decreased as the GPS increased (p = 0.016). The GPS is a significant prognostic factor in CRC and should be included in the routine preoperative assessment of all surgically treated CRC patients. PMID:26925798

  9. OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer

    PubMed Central

    Weixler, Benjamin; Cremonesi, Eleonora; Sorge, Roberto; Muraro, Manuele Giuseppe; Delko, Tarik; Nebiker, Christian A.; Däster, Silvio; Governa, Valeria; Amicarella, Francesca; Soysal, Savas D.; Kettelhack, Christoph; von Holzen, Urs W.; Eppenberger-Castori, Serenella; Spagnoli, Giulio C.; Oertli, Daniel; Iezzi, Giandomenica; Terracciano, Luigi; Tornillo, Luigi

    2015-01-01

    Background OX40 is a TNF receptor family member expressed by activated T cells. Its triggering by OX40 ligand promotes lymphocyte survival and memory generation. Anti-OX40 agonistic monoclonal antibodies (mAb) are currently being tested in cancer immunotherapy. We explored the prognostic significance of tumor infiltration by OX40+ cells in a large colorectal cancer (CRC) collective. Methods OX40 gene expression was analyzed in 50 freshly excised CRC and corresponding healthy mucosa by qRT-PCR. A tissue microarray including 657 clinically annotated CRC specimens was stained with anti-OX40, -CD8 and -FOXP3 mAbs by standard immunohistochemistry. The CRC cohort was randomly split into training and validation sets. Correlations between CRC infiltration by OX40+ cells alone, or in combination with CD8+ or FOXP3+ cells, and clinical-pathological data and overall survival were comparatively evaluated. Results OX40 gene expression in CRC significantly correlated with FOXP3 and CD8 gene expression. High CRC infiltration by OX40+ cells was significantly associated with favorable prognosis in training and validation sets in univariate, but not multivariate, Cox regression analysis. CRC with OX40high/CD8high infiltration were characterized by significantly prolonged overall survival, as compared to tumors with OX40low/CD8high, OX40high/CD8low or OX40low/CD8low infiltration in both uni- and multivariate analysis. In contrast, prognostic significance of OX40+ and FOXP3+ cell infiltration was not enhanced by a combined evaluation. Irrespective of TNM stage, CRC with OX40high/CD8high density infiltrates showed an overall survival similar to that of all stage I CRC included in the study. Conclusions OX40high/CD8high density tumor infiltration represents an independent, favorable, prognostic marker in CRC with an overall survival similar to stage I cancers. PMID:26439988

  10. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma

    PubMed Central

    Shen, G H; Ghazizadeh, M; Kawanami, O; Shimizu, H; Jin, E; Araki, T; Sugisaki, Y

    2000-01-01

    The influence of vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) on prognosis and the relationship between VEGF expression and MVD in ovarian carcinoma are not well defined. We studied VEGF expression in parallel with MVD by immunohistochemistry in 94 ovarian tumours (64 malignant, 13 borderline, and 17 benign) and correlated the results with the clinicopathologic prognostic factors of the disease to clarify their significance in this disease. Assessment of VEGF mRNA isoforms by RT-PCR was also performed. Of the malignant, borderline, and benign ovarian tumours respectively, two (3%), four (31%) and 16 (94%) were negative, 31 (48%), seven (54%) and one (6%) had low expressions, and 31 (48%), two (15%) and none (0%) had high expressions of VEGF. There were significant associations between the VEGF expression and disease stage (P = 0.002), histologic grade (P = 0.0004), and patient outcome (P = 0.0002). MVD did not correlate significantly with the clinicopathologic parameters. Likewise, no correlation was found between MVD and VEGF expression. The survival of patients with high VEGF expression was significantly worse than that of patients with low and negative VEGF expression (P = 0.0004). Multivariate analysis revealed that disease stage and VEGF expression were significant and independent prognostic indicators of overall survival time (P = 0.008 and P = 0.006 respectively). These findings suggest that in conjunction with the established clinicopathologic prognostic parameters of ovarian carcinoma, VEGF expression may enhance the predictability of patients at high risk for tumour progression who are potential candidates for further aggressive therapy. © 2000 Cancer Research Campaign PMID:10901370

  11. KiSS-1 expression in oral squamous cell carcinoma and its prognostic significance.

    PubMed

    Shin, Wui-Jung; Cho, Young-Ah; Kang, Kyung-Rim; Kim, Ji-Hoon; Hong, Seong-Doo; Lee, Jae-Il; Hong, Sam-Pyo; Yoon, Hye-Jung

    2016-04-01

    Downregulated expression of KiSS-1 has been correlated with tumor progression, metastasis, and patient prognosis in various human malignancies. However, there is no information regarding the expression of KiSS-1 in oral squamous cell carcinoma (OSCC). Our aims were to examine KiSS-1 expression in OSCC tissue samples and cell lines and to determine its prognostic significance. KiSS-1 expression was significantly lower in lymph node (LN) metastases than in primary tumor tissues. Five of six OSCC cell lines showed absence or relatively low expression of KiSS-1. Correlations between KiSS-1 expression and clinicopathological parameters were statistically assessed. There were significant correlations between KiSS-1 expression and LN metastasis (p = 0.007), TNM stage (p = 0.024), and local recurrence (p = 0.012). In the Kaplan-Meier survival analysis, negative KiSS-1 expression significantly correlated with poorer overall survival (OS) and disease-free survival (DFS) (p = 0.000 and 0.000, respectively). Multivariate analysis using Cox regression modeling revealed that KiSS-1 expression was an independent prognostic factor for both OS and DFS (p = 0.001 and 0.000, respectively). Our findings suggested that KiSS-1 downregulation may play a role in tumor progression and metastasis of OSCC and may be a reliable biomarker for predicting clinical outcome in OSCC. PMID:26809635

  12. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients.

    PubMed

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke; Trapman-Jansen, Anita M A C; Foekens, Renée; Look, Maxime P; Smid, Marcel; van Deurzen, Carolien H M; Span, Paul N; Sweep, Fred C G J; Brask, Julie Benedicte; Timmermans-Wielenga, Vera; Foekens, John A; Martens, John W M; Umar, Arzu

    2016-01-01

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules. PMID:27558661

  13. Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

    PubMed Central

    Liu, Ning Qing; De Marchi, Tommaso; Timmermans, Annemieke; Trapman-Jansen, Anita M. A. C.; Foekens, Renée; Look, Maxime P.; Smid, Marcel; van Deurzen, Carolien H. M.; Span, Paul N.; Sweep, Fred C. G. J.; Brask, Julie Benedicte; Timmermans-Wielenga, Vera; Foekens, John A.; Martens, John W. M.; Umar, Arzu

    2016-01-01

    We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules. PMID:27558661

  14. The Glasgow Prognostic Score (GPS) as a novel and significant predictor of extranodal natural killer/T-cell lymphoma, nasal type.

    PubMed

    Li, Ya-Jun; Jiang, Wen-Qi; Huang, Jia-Jia; Xia, Zhong-Jun; Huang, Hui-Qiang; Li, Zhi-Ming

    2013-05-01

    The Glasgow Prognostic Score (GPS), an inflammation-based prognostic score including C-reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T-cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T-cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more adverse clinical characteristics, lower rates of complete remission (P < 0.001), inferior progression-free survival (PFS, P < 0.001), and inferior overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low-risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL. PMID:23423859

  15. CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer

    PubMed Central

    2012-01-01

    Introduction Tumor infiltrating lymphocytes may indicate an immune response to cancer development, but their significance remains controversial in breast cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte infiltration in a large cohort of invasive early stage breast cancers, and to evaluate its prognostic effect in different breast cancer intrinsic subtypes. Methods Immunohistochemistry for CD8 staining was performed on tissue microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes were counted as intratumoral when in direct contact with tumor cells, and as stromal in adjacent locations. Kaplan-Meier functions and Cox proportional hazards regression models were applied to examine the associations between tumor infiltrating lymphocytes and breast cancer specific survival. Results Among 3403 cases for which immunohistochemical results were obtained, CD8+ tumor infiltrating lymphocytes were identified in an intratumoral pattern in 32% and stromal pattern in 61% of the cases. In the whole cohort, the presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival. Multivariate analysis indicated that the favorable prognostic effect of CD8+ tumor infiltrating lymphocytes was significant only in the core basal intrinsic subgroup (Hazard ratio, HR = 0.35, 95% CI = 0.23-0.54). No association with improved survival was present in those triple negative breast cancers that lack expression of basal markers (HR = 0.99, 95% CI = 0.48-2.04) nor in the other intrinsic subtypes. Conclusions CD8+ tumor infiltrating lymphocytes are an independent prognostic factor associated with better patient survival in basal-like breast cancer, but not in non-basal triple negative breast cancers nor in other intrinsic

  16. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy

    PubMed Central

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol’s efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  17. Circulating Tumour Cells as an Independent Prognostic Factor in Patients with Advanced Oesophageal Squamous Cell Carcinoma Undergoing Chemoradiotherapy.

    PubMed

    Su, Po-Jung; Wu, Min-Hsien; Wang, Hung-Ming; Lee, Chia-Lin; Huang, Wen-Kuan; Wu, Chiao-En; Chang, Hsien-Kun; Chao, Yin-Kai; Tseng, Chen-Kan; Chiu, Tzu-Keng; Lin, Nina Ming-Jung; Ye, Siou-Ru; Lee, Jane Ying-Chieh; Hsieh, Chia-Hsun

    2016-01-01

    The role of circulating tumour cells (CTCs) in advanced oesophageal cancer (EC) patients undergoing concurrent chemoradiotherapy (CCRT) remains uncertain. A negative selection protocol plus flow cytometry was validated to efficiently identify CTCs. The CTC number was calculated and analysed for survival impact. The protocol's efficacy in CTC identification was validated with a recovery rate of 44.6 ± 9.1% and a coefficient of variation of 20.4%. Fifty-seven patients and 20 healthy donors were enrolled. Initial staging, first response to CRT, and surgery after CRT were prognostic for overall survival, with P values of <0.0001, <0.0001, and <0.0001, respectively. The CTC number of EC patients is significantly higher (P = 0.04) than that of healthy donors. Multivariate analysis for disease-specific progression-free survival showed that surgery after response to CCRT, initial stage, and CTC number (≥21.0 cells/mL) played independent prognostic roles. For overall survival, surgery after CCRT, performance status, initial stage, and CTC number were significant independent prognostic factors. In conclusion, a negative selection plus flow cytometry protocol efficiently detected CTCs. The CTC number before CCRT was an independent prognostic factor in patients with unresectable oesophageal squamous cell carcinoma. Further large-scale prospective studies for validation are warranted. PMID:27530152

  18. Immunohistochemical profiles of IDH1, MGMT and P53: practical significance for prognostication of patients with diffuse gliomas.

    PubMed

    Ogura, Ryosuke; Tsukamoto, Yoshihiro; Natsumeda, Manabu; Isogawa, Mizuho; Aoki, Hiroshi; Kobayashi, Tsutomu; Yoshida, Seiichi; Okamoto, Kouichiro; Takahashi, Hitoshi; Fujii, Yukihiko; Kakita, Akiyoshi

    2015-08-01

    Genetic and epigenetic status, including mutations of isocitrate dehydrogenase (IDH) and TP53 and methylation of O(6) -methylguanine-DNA methyltransferase (MGMT), are associated with the development of various types of glioma and are useful for prognostication. Here, using routinely available histology sections from 312 patients with diffuse gliomas, we performed immunohistochemistry using antibodies specific for IDH1 mutation, MGMT methylation status, and aberrant p53 expression to evaluate the possible prognostic significance of these features. With regard to overall survival (OS), univariate analysis indicated that an IDH1-positive profile in patients with glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligoastrocytoma and oligodendroglioma, or a MGMT-negative profile in patients with GBM and AA were significantly associated with a favorable outcome. Multivariate analysis revealed that both profiles were independent factors influencing prognosis. The OS of patients with IDH1-positive/MGMT-negative profiles was significantly longer than that of patients with negative/negative and negative/positive profiles. A p53 profile was not an independent prognostic factor. However, for GBM/AA patients with IDH1-negative/MGMT-negative profiles, p53 overexpression was significantly associated with an unfavorable outcome. Thus, the immunohistochemical profiles of IDH1 and MGMT are of considerable significance in gliomas, and a combination of IDH1, MGMT and p53 profiles may be useful for prognostication of GBM/AA. PMID:25950388

  19. Downregulation of MTSS1 expression is an independent prognosticator in squamous cell carcinoma of the lung

    PubMed Central

    Kayser, G; Csanadi, A; Kakanou, S; Prasse, A; Kassem, A; Stickeler, E; Passlick, B; zur Hausen, A

    2015-01-01

    Background: The metastasis suppressor 1 (MTSS1) is a newly discovered protein putatively involved in tumour progression and metastasis. Material and Methods: Immunohistochemical expression of MTSS1 was analysed in 264 non-small-cell lung carcinomas (NSCLCs). Results: The metastasis suppressor 1 was significantly overexpressed in NSCLC compared with normal lung (P=0.01). Within NSCLC, MTSS1 expression was inversely correlated with pT-stage (P=0.019) and histological grading (P<0.001). NSCLC with MTSS1 downregulation (<20%) showed a significantly worse outcome (P=0.007). This proved to be an independent prognostic factor in squamous cell carcinomas (SCCs; P=0.041), especially in early cancer stages (P=0.006). Conclusion: The metastasis suppressor 1 downregulation could thus serve as a stratifying marker for adjuvant therapy in early-stage SCC of the lung. PMID:25625275

  20. Prognostic significance of metastatic lymph node ratio in squamous cell carcinoma of the cervix

    PubMed Central

    Li, Chen; Liu, Wenhui; Cheng, Yufeng

    2016-01-01

    Purpose Metastatic lymph node ratio (MLNR) was reported to be an important prognostic factor in several tumors. However, depth of primary tumor invasion is also important in cervical cancer prognostic analysis. In this study, the objective was to determine if MLNR can be used to define a high-risk category of patients with squamous cell carcinoma of the cervix (SCC). And we combined MLNR and depth of invasion to investigate whether prognosis of SCC can be predicted better. Patients and methods We performed a retrospective review of patients with SCC who underwent radical hysterectomy and pelvic lymphadenectomy at QiLu Hospital of Shandong University from January 2007 to December 2009. Prognostic factors for disease-free survival (DFS) and overall survival (OS) were identified by univariate and multivariate analyses. Results One hundred and ninety-eight patients met the inclusion criteria and were included in the analysis. By cut-point survival analysis, MLNR cutoff was designed as 0.2. On multivariate analysis, an MLNR >0.2 was associated with a worse OS (hazard ratio [HR] =2.560, 95% CI 1.275–5.143, P=0.008) and DFS (HR =2.404, 95% CI 1.202–4.809, P=0.013). Depth of invasion cutoff was designed as invasion >1/2 cervix wall and was associated with a worse OS (HR =1.806, 95% CI 1.063–3.070, P=0.029) and DFS (HR =1.900, 95% CI 1.101–3.279, P=0.021). In addition, subgroup analysis revealed significant difference in OS and DFS rates between different MLNR categories within the same depth of invasion category (P<0.05), however, not between different depth of invasion categories within the same MLNR category (P>0.05). Conclusion MLNR may be used as the independent prognostic parameter in patients with SCC. Combined MLNR and depth of invasion can predict both OS and DFS better in SCC than one factor. Besides, MLNR appears to be a better prognostic value than depth of invasion for SCC. PMID:27382315

  1. Cathepsin S expression: An independent prognostic factor in glioblastoma tumours--A pilot study.

    PubMed

    Flannery, Thomas; McQuaid, Stephen; McGoohan, Caroline; McConnell, Robert S; McGregor, Gordon; Mirakhur, Meenakshi; Hamilton, Peter; Diamond, James; Cran, Gordon; Walker, Brian; Scott, Christopher; Martin, Lorraine; Ellison, David; Patel, Chirag; Nicholson, Clare; Mendelow, David; McCormick, Derek; Johnston, Patrick G

    2006-08-15

    Cysteine proteinases have been implicated in astrocytoma invasion. We recently demonstrated that cathepsin S (CatS) expression is up-regulated in astrocytomas and provided evidence for a potential role in astrocytoma invasion (Flannery et al., Am J Path 2003;163(1):175-82). We aimed to evaluate the significance of CatS in human astrocytoma progression and as a prognostic marker. Frozen tissue homogenates from 71 patients with astrocytomas and 3 normal brain specimens were subjected to ELISA analyses. Immunohistochemical analysis of CatS expression was performed on 126 paraffin-embedded tumour samples. Fifty-one astrocytoma cases were suitable for both frozen tissue and paraffin tissue analysis. ELISA revealed minimal expression of CatS in normal brain homogenates. CatS expression was increased in grade IV tumours whereas astrocytoma grades I-III exhibited lower values. Immunohistochemical analysis revealed a similar pattern of expression. Moreover, high-CatS immunohistochemical scores in glioblastomas were associated with significantly shorter survival (10 vs. 5 months, p = 0.014). With forced inclusion of patient age, radiation dose and Karnofsky score in the Cox multivariate model, CatS score was found to be an independent predictor of survival. CatS expression in astrocytomas is associated with tumour progression and poor outcome in glioblastomas. CatS may serve as a useful prognostic indicator and potential target for anti-invasive therapy. PMID:16550604

  2. Proposal for a Standardized Pathology Report of Gastroenteropancreatic Neuroendocrine Tumors: Prognostic Significance of Pathological Parameters

    PubMed Central

    Cho, Mee-Yon; Jin, So Young; Kim, Hyunki; Jung, Eun Sun; Kim, Mi-Jung; Kim, Kyoung-Mee; Kim, Woo Ho; Kim, Joon Mee; Kang, Yun Kyung; Choi, Joon Hyuk; Kang, Dae Young; Kim, Youn Wha; Choi, Eun Hee

    2013-01-01

    Background There is confusion in the diagnosis and biological behaviors of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), because of independently proposed nomenclatures and classifications. A standardized form of pathology report is required for the proper management of patients. Methods We discussed the proper pathological evaluation of GEP-NET at the consensus conference of the subcommittee meeting for the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. We then verified the prognostic significance of pathological parameters from our previous nationwide collection of pathological data from 28 hospitals in Korea to determine the essential data set for a pathology report. Results Histological classification, grading (mitosis and/or Ki-67 labeling index), T staging (extent, size), lymph node metastasis, and lymphovascular and perineural invasion were significant prognostic factors and essential for the pathology report of GEP-NET, while immunostaining such as synaptophysin and chromogranin may be optional. Furthermore, the staging system, either that of the 2010 American Joint Cancer Committee (AJCC) or the European Neuroendocrine Tumor Society (ENETS), should be specified, especially for pancreatic neuroendocrine neoplasms. Conclusions A standardized pathology report is crucial for the proper management and prediction of prognosis of patients with GEP-NET. PMID:23837015

  3. Prognostic significance of Ki-67 index value at the primary breast tumor in recurrent breast cancer

    PubMed Central

    NISHIMURA, REIKI; OSAKO, TOMOFUMI; NISHIYAMA, YASUYUKI; TASHIMA, RUMIKO; NAKANO, MASAHIRO; FUJISUE, MAMIKO; TOYOZUMI, YASUO; ARIMA, NOBUYUKI

    2014-01-01

    in the primary tumor as an independent significant factor, particularly in luminal type tumors. The Ki-67 index value in the primary tumor was a significant prognostic factor for OS after disease recurrence. It is, therefore, important to take the Ki-67 index value into consideration for the treatment and follow-up of breast cancer patients. PMID:25279198

  4. Prognostic significance of CXCL12, CXCR4, and CXCR7 in patients with breast cancer

    PubMed Central

    Wu, Wei; Qian, Liyuan; Chen, Xuedong; Ding, Boni

    2015-01-01

    Background: The chemokine CXCL12 and its receptors CXCR4 and CXCR7 play important roles in cancer invasion and metastasis. This study investigated the mRNA expressions of CXCL12, CXCR4, and CXCR7 to illustrate the role of these biomarkers in breast cancer metastasis and prognosis. Methods: The mRNA expressions of CXCL12, CXCR4, and CXCR7 in 115 primary breast cancer and regional lymph node specimens were detected by quantitative reverse-transcription polymerase chain reaction. Survival time was analyzed by Kaplan-Meier survival curves using log-rank test. Univariable and multivariable Cox regression analyses were performed to assess independent prognostic factors for survival. Results: The expression levels of CXCR4 and CXCR7 in breast cancer tissues were significantly higher than that in adjacent normal tissues (P=0.022 and P<0.001, respectively), while the expression level of CXCL12 in breast cancer tissues did not differ from that in adjacent normal tissues (P=0.156). Furthermore, CXCL12 exhibited significant differences in expression between primary tumor and lymph node metastasis tumor (P=0.039). CXCR4 and CXCR7 expressions in metastasis tumor were also higher, although no significant difference was observed (P=0.067 and P=0.054, respectively). Kaplan-Meier survival analysis revealed that patients exhibiting high CXCR4 and CXCR7 expression experienced a shorter survival period compared with those with low expression. When analyzed with a Cox regression model, the expressions of CXCL12, CXCR4 and CXCR7 were independent prognostic factors for overall survival. Conclusions: The mRNA expressions of CXCL12, CXCR4, and CXCR7 play important roles in the progression and metastasis of breast cancer and may act as predictive factors significantly affecting the prognosis. PMID:26722521

  5. Prognostic significance of DNA aneuploidy in diffuse malignant mesothelioma

    SciTech Connect

    Isobe, Hiroshi; Sridhar, K.S.; Doria, R.

    1995-01-01

    DNA ploidy of pepsin digested preparations of 48 paraffin-embedded specimens from 19 patients with histologically confirmed malignant mesothelioma was determined by laser flow cytometry. Eight of the 19 tumors (42%) were diploid and 11 (58%) were aneuploid. Of the aneuploid tumors, only one showed multiploidy. The median survival time of the patients with diploid tumors was 19, 16, and 14 months from the onset of symptoms, diagnosis, and treatment, respectively. The median survival in patients with aneuploid tumors was 8, 7, and 7 months from the onset of first symptoms, diagnosis, and treatment. Thus, patients with diploid tumors lived longer than patients with aneuploid tumors. These results suggest that DNA ploidy analysis may be of prognostic value in malignant mesothelioma. 31 refs., 2 figs., 3 tabs.

  6. Prognostic significance of Dicer expression in hepatocellular carcinoma

    PubMed Central

    ZHANG, LI; WANG, CUIJU; LIU, SHUFENG; ZHAO, YUFEI; LIU, CHAO; GUO, ZHANJUN

    2016-01-01

    Dicer is a RNaseIII endonuclease of the microRNA processing pathway, which is implicated in carcinogenesis of various types of human cancer. The present study assessed the expression level of Dicer in hepatocellular carcinoma (HCC) tissue to evaluate its association with HCC tumorigenesis. A low expression of Dicer was significantly associated with a shorter postoperative survival time of patients with HCC, which was assessed using the log-rank test with Kaplan-Meier survival analysis. Multivariate analysis identified that Dicer expression was an independent predictor for HCC outcome (relative risk, 0.660; 95% confidence interval, 0.506–0.861; P=0.002). A functional assay demonstrated that Dicer overexpression inhibited the proliferation and promoted the apoptosis of HCC cells. In addition, a Transwell assay revealed that Dicer markedly inhibited the migration and invasion of HCC cells. The present findings indicate that Dicer expression modified the outcomes of HCC patients by inhibiting proliferation, promoting apoptosis and inhibiting metastasis of HCC cells. PMID:27313724

  7. FBXW7 acts as an independent prognostic marker and inhibits tumor growth in human osteosarcoma.

    PubMed

    Li, Zhanchun; Xiao, Jie; Hu, Kongzu; Wang, Gang; Li, Maoqiang; Zhang, Jidong; Cheng, Guangqi

    2015-01-01

    F-box and WD repeat domain-containing 7 (FBXW7) is a potent tumor suppressor in human cancers including breast cancer, colorectal cancer, gastric cancer and hepatocellular carcinoma. In this study, we found that the expressions of FBXW7 protein and mRNA levels in osteosarcoma (OS) cases were significantly lower than those in normal bone tissues. Clinical analysis indicated that FBXW7 was expressed at lower levels in OS patients with advanced clinical stage, high T classification and poor histological differentiation. Furthermore, we demonstrated that high expression of FBXW7 was correlated with a better 5-year survival of OS patients. Multivariate Cox regression analysis indicated that FBXW7 was an independent prognostic marker in OS. Our in vitro studies showed that FBXW7 overexpression inhibited cell cycle transition and cell proliferation, and promoted apoptosis in both U2OS and MG-63 cells. In a nude mouse xenograft model, FBXW7 overexpression slowed down tumor growth by inducing apoptosis and growth arrest. Mechanistically, FBXW7 inversely regulated oncoprotein c-Myc and cyclin E levels in both U2OS and MG-63 cells. Together these findings suggest that FBXW7 may serve as a prognostic biomarker and inhibit tumor progression by inducing apoptosis and growth arrest in OS. PMID:25622249

  8. EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma.

    PubMed

    Caudron, Anne; Battistella, Maxime; Feugeas, Jean-Paul; Pages, Cécile; Basset-Seguin, Nicole; Mazouz Dorval, Sarra; Funck Brentano, Elisa; Sadoux, Aurélie; Podgorniak, Marie-Pierre; Menashi, Suzanne; Janin, Anne; Lebbé, Céleste; Mourah, Samia

    2016-08-01

    CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P < 0.05 for both) in primary melanoma patients. CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P < 10(-8) ). Multivariate analysis retained CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P < 0.05 for both). CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker. PMID:27060463

  9. Wilms' tumor gene 1 expression: an independent acute leukemia prognostic indicator following allogeneic hematopoietic SCT.

    PubMed

    Zhao, X-S; Jin, S; Zhu, H-H; Xu, L-P; Liu, D-H; Chen, H; Liu, K-Y; Huang, X-J

    2012-04-01

    To evaluate the prognostic significance of Wilms' tumor gene 1 (WT1) expression for monitoring minimal residual disease and predicting relapse in patients with acute leukemia (AL) following allogeneic hematopoietic SCT (allo-HSCT), the WT1 expression levels of 138 AL patients were measured using real-time quantitative reverse transcription PCR at designed time points after allo-HSCT. All patients were divided into four groups based on the HSCT outcomes and intervention application. A low level of WT1 expression following HSCT indicated a low risk of relapse, whereas WT1 expression >1.05% was indicative of a higher probability of relapse. Only the advanced stage of disease (hazard ratio (HR)=2.73; 95% confidence interval (CI)=1.337-5.573, P=0.006) and a WT1 expression ≥ 0.60% (HR=4.774; 95% CI=2.410-9.459, P=0.000) were associated with lower disease-free survival. Relapse (HR=0.119; 95% CI=0.056-0.250, P=0.000) and a WT1 expression 0.60% (HR=2.771; 95% CI=1.316-5.834, P=0.007) were associated with lower OS. In conclusion, the WT1 expression level is an independent prognostic factor that can predict clinical outcomes for AL patients after HSCT and provide a guide for suitable interventions. PMID:21643023

  10. Serum alpha-fetoprotein surge after the initiation of chemotherapy for non-seminomatous testicular cancer has an adverse prognostic significance.

    PubMed Central

    de Wit, R.; Collette, L.; Sylvester, R.; de Mulder, P. H.; Sleijfer, D. T.; ten Bokkel Huinink, W. W.; Kaye, S. B.; van Oosterom, A. T.; Boven, E.; Stoter, G.

    1998-01-01

    It has been recognized that the tumour markers alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) may show a transient elevation after the initiation of chemotherapy in non-seminomatous testicular cancer. We investigated the prognostic importance of these so-called marker surges in a cohort of patients treated with cisplatin combination chemotherapy between 1983 and 1991. A total of 669 patients were studied. Of 352 patients who had an elevated AFP at the start of treatment and for whom we had data at both day 1 and day 8, 101 (29%) had a surge. Of 317 patients for whom we had data for HCG, 80 patients (25%) had a surge. It was found that an AFP surge was a strong adverse prognostic factor for progression [hazard ratio (HR) 2.28, P=0.005]. There was no statistically significant difference in survival (HR 1.65, P=0.13). There was no prognostic significance of a HCG surge, either for progression or for survival. To investigate whether a surge was an independent prognostic factor for progression and survival, multivariate Cox regression models were fitted using the independent prognostic factors for progression and survival and the surge/decline variable. An AFP surge was retained in the final model for progression. A HCG surge was of no prognostic importance for progression or survival. We conclude that an AFP surge has an adverse prognostic significance, independent of pretreatment characteristics. PMID:9823978

  11. Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas.

    PubMed

    Grange, Florent; Petrella, Tony; Beylot-Barry, Marie; Joly, Pascal; D'Incan, Michel; Delaunay, Michele; Machet, Laurent; Avril, Marie-Francoise; Dalac, Sophie; Bernard, Philippe; Carlotti, Agnes; Esteve, Eric; Vergier, Beatrice; Dechelotte, Pierre; Cassagnau, Elisabeth; Courville, Philippe; Saiag, Philippe; Laroche, Liliane; Bagot, Martine; Wechsler, Janine

    2004-05-15

    Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions. PMID:14726400

  12. Expression and prognostic significance of the polymeric immunoglobulin receptor in esophageal and gastric adenocarcinoma

    PubMed Central

    2014-01-01

    Introduction The polymeric immunoglobulin receptor (PIGR) has been proposed to be a candidate prognostic biomarker in a few cancer forms, and one previous study reported that reduced PIGR expression signifies more aggressive tumours of the distal esophagus and gastroesophageal junction (GEJ). In the present study, we examined the expression, clinicopathological correlates and prognostic significance of PIGR expression in an extended cohort of adenocarcinoma of the upper gastrointestinal tract. Materials and methods Immunohistochemical PIGR expression was examined in a consecutive cohort of patients with surgically resected, radio-chemonaive adenocarcinoma of the esophagus, GE-junction and stomach (n = 173), including paired samples of benign-appearing squamous epithelium (n = 51), gastric mucosa (n = 114), Barrett’s esophagus (BE) or intestinal metaplasia (IM) (n = 57) and lymph node metastases (n = 75). Non-parametric tests were applied to explore associations between PIGR expression in primary tumours and clinicopathological characteristics. Classification and regression tree analysis was applied for selection of prognostic cut-off. The impact of PIGR expression on overall survival (OS) and recurrence-free survival (RFS) was assessed by Kaplan-Meier analysis and hazard ratios (HR) calculated by adjusted and unadjusted Cox proportional hazards modelling. Results PIGR expression was significantly higher in intestinal metaplasia (BE or gastric IM) compared to normal tissues and cancer (p < 0.001). Reduced PIGR expression in primary tumours was significantly associated with more advanced tumour stage (p = 0.002) and inversely associated with involved margins (p = 0.034). PIGR expression did not differ between primary tumours and lymph node metastases. There was no significant difference in PIGR expression between tumours with and without a background of intestinal metaplasia. High PIGR expression was an independent predictor of a

  13. Prognostic Significance of MiR-34a Expression in Patients with Gastric Cancer after Radical Gastrectomy

    PubMed Central

    Hui, Wen-Tao; Ma, Xiao-Bin; Zan, Ying; Wang, Xi-Jing; Dong, Lei

    2015-01-01

    Background: MiR-34a dysregulation has been implicated in tumorigenesis and progression of gastric cancer, but its role in prognosis of patients with gastric cancer remains unknown. The aim of this study was to investigate the expression and prognostic significance of miR-34a in gastric cancer patients after radical gastrectomy. Methods: Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-34a in human gastric cancer cell lines and tissues in 76 patients with gastric adenocarcinoma from China. Results are assessed for association with clinical features and overall survival (OS) using Kaplan–Meier analysis. Prognostic values of miR-34a expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating miR-34a expression was determined using receiver operating characteristic analysis. Results: The results show that the expression level of miR-34a was decreased in human gastric cancer cell lines and tissues, and down-regulated expression of miR-34a was associated with Lauren classification (P = 0.034). Decreased miR-34a expression in gastric cancer tissues was positively correlated with poor OS of gastric cancer patients (P = 0.013). Further multivariate Cox regression analysis suggested that miR-34a expression was an independent prognostic indicator for gastric cancer (P = 0.027). Applying the prognostic value of miR-34a expression to tumor node metastasis (TNM) stage system showed a better prognostic value in patients with gastric cancer than miR-34a expression (P = 0.0435) or TNM stage (P = 0.0249) alone. Conclusion: The results reinforce the critical role for the down-regulated miR-34a expression in gastric cancer and suggest that miR-34a could be a prognostic indicator for this disease. PMID:26415802

  14. Prognostic significance of lymphangiogenesis in pharyngolaryngeal carcinoma patients

    PubMed Central

    2010-01-01

    Background Lymphatic vessel spread is considered a major route for head and neck squamous cell carcinoma metastasis. Formation of new lymphatic vessels could facilitate the process, raising the malignant potential of these tumours. Recent identification of lymphatic markers allows the study of the lymphangiogenesis phenomenon. We searched for molecular events involved in the lymphangiogenic process that could have prognostic value in laryngeal/pharyngeal carcinoma patients. Methods 104 paraffin-embedded pharyngeal/laryngeal tumour samples were studied. Immunohistochemical analysis of podoplanin and double immunofluorescence analysis of Ki-67 and D2-40 were performed. Lymph vessel density (inside the tumour mass, at its periphery or considered as a whole) and the presence of tumour emboli inside lymphatics were recorded. The proliferative state of endothelial lymphatic cells was evaluated. Results Lymphatic vessels were detected inside the tumour mass (75%) and in the surrounding tissue (80%); some of them in a proliferative state. Tumour emboli were detected in a high proportion of the cases (45%). Lymphatic vessel density was higher in the pharyngeal cases (p = 0.0029), in greater size (p = 0.039), more advanced stage primary tumours (p = 0.006) and in carcinomas of patients with affected nodes (p = 0.019). The presence of tumour emboli and a high global vessel density were indicators of poor prognosis (recorded as death from tumour) in the laryngeal group (p = 0.015 and p = 0.027, respectively), but notably not in the pharyngeal one. Interestingly, high global vessel density showed a negative prognostic value among pathologically staged N0 laryngeal carcinomas (p = 0.03). Conclusions The lymphangiogenic process correlated with aggressive tumour features (pN category, tumour size, tumour stage), but might play different roles in tumours arising from different anatomic sites. Our results suggest that detection of tumour emboli and assessment of global vessel

  15. Prognostic Significance of POLE Proofreading Mutations in Endometrial Cancer

    PubMed Central

    Church, David N.; Stelloo, Ellen; Nout, Remi A.; Valtcheva, Nadejda; Depreeuw, Jeroen; ter Haar, Natalja; Noske, Aurelia; Amant, Frederic; Wild, Peter J.; Lambrechts, Diether; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Smit, Vincent T. H. B. M.; Creutzberg, Carien L.; Bosse, Tjalling

    2015-01-01

    Background: Current risk stratification in endometrial cancer (EC) results in frequent over- and underuse of adjuvant therapy, and may be improved by novel biomarkers. We examined whether POLE proofreading mutations, recently reported in about 7% of ECs, predict prognosis. Methods: We performed targeted POLE sequencing in ECs from the PORTEC-1 and -2 trials (n = 788), and analyzed clinical outcome according to POLE status. We combined these results with those from three additional series (n = 628) by meta-analysis to generate multivariable-adjusted, pooled hazard ratios (HRs) for recurrence-free survival (RFS) and cancer-specific survival (CSS) of POLE-mutant ECs. All statistical tests were two-sided. Results: POLE mutations were detected in 48 of 788 (6.1%) ECs from PORTEC-1 and-2 and were associated with high tumor grade (P < .001). Women with POLE-mutant ECs had fewer recurrences (6.2% vs 14.1%) and EC deaths (2.3% vs 9.7%), though, in the total PORTEC cohort, differences in RFS and CSS were not statistically significant (multivariable-adjusted HR = 0.43, 95% CI = 0.13 to 1.37, P = .15; HR = 0.19, 95% CI = 0.03 to 1.44, P = .11 respectively). However, of 109 grade 3 tumors, 0 of 15 POLE-mutant ECs recurred, compared with 29 of 94 (30.9%) POLE wild-type cancers; reflected in statistically significantly greater RFS (multivariable-adjusted HR = 0.11, 95% CI = 0.001 to 0.84, P = .03). In the additional series, there were no EC-related events in any of 33 POLE-mutant ECs, resulting in a multivariable-adjusted, pooled HR of 0.33 for RFS (95% CI = 0.12 to 0.91, P = .03) and 0.26 for CSS (95% CI = 0.06 to 1.08, P = .06). Conclusion: POLE proofreading mutations predict favorable EC prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors. This novel biomarker may help to reduce overtreatment in EC. PMID:25505230

  16. Prognostic Significance of Preoperative Albumin-Globulin Ratio in Patients with Upper Tract Urothelial Carcinoma

    PubMed Central

    Zhou, Li-Qun; He, Zhi-Song; Shen, Cheng; He, Qun; Li, Jun; Liu, Li-Bo; Wang, Cong; Chen, Xiao-Yu; Fan, Yu; Hu, Shuai; Zhang, Lei; Han, Wen-Ke; Jin, Jie

    2015-01-01

    Background Preoperative albumin-globulin ratio (AGR) reflects both malnutrition and systemic inflammation in cancer patients. In particular, systemic inflammation has been reported to contribute to tumor progression and poor oncological outcome in various malignancies. However, the prognostic value of preoperative AGR in upper tract urothelial carcinoma (UTUC) has not been examined. Methods We retrospectively reviewed medical data of 187 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). AGR was calculated as [AGR = albumin/(serum total protein—albumin)]. The associations of preoperative AGR with clinicopathologic characteristics and prognosis were assessed. Multivariate analyses using Cox regression models were performed to determine the independent prognostic factors. Results The median (IQR) preoperative AGR was 1.50 (1.30–1.70), and the optimal cutoff value was determined to be 1.45 according to the receiver operating curve analysis. Low AGR was significantly associated with female gender, high CKD stage and tumor grade (P < 0.05). Eighty-three patients died before the follow-up endpoint. Kaplan-Meier analysis showed that an AGR < 1.45 predicted significantly poorer overall and cancer-specific survivals compared to an AGR ≥ 1.45 (P < 0.001 and P = 0.008, respectively). Multivariate analyses showed that an AGR < 1.45 was an independent risk factor for poorer overall and cancer-specific survivals (P = 0.002 and P = 0.015, respectively). Conclusions Preoperative AGR can act as an effective biomarker with easy accessibility for evaluating the prognosis of patients with UTUC. AGR should be applied in UTUC patients for risk stratification and determination of optimal therapeutic regimens. PMID:26681341

  17. Primary tumor regression speed after radiotherapy and its prognostic significance in nasopharyngeal carcinoma: a retrospective study

    PubMed Central

    2014-01-01

    Background To observe the primary tumor (PT) regression speed after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) and evaluate its prognostic significance. Methods One hundred and eighty-eight consecutive newly diagnosed NPC patients were reviewed retrospectively. All patients underwent magnetic resonance imaging and fiberscope examination of the nasopharynx before RT, during RT when the accumulated dose was 46–50 Gy, at the end of RT, and 3–4 months after RT. Results Of 188 patients, 40.4% had complete response of PT (CRPT), 44.7% had partial response of PT (PRPT), and 14.9% had stable disease of PT (SDPT) at the end of RT. The 5-year overall survival (OS) rates for patients with CRPT, PRPT, and SDPT at the end of RT were 84.0%, 70.7%, and 44.3%, respectively (P < 0.001, hazard ratio [HR] = 2.177, 95% confidence interval [CI] = 1.480-3.202). The 5-year failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates also differed significantly (87.8% vs. 74.3% vs. 52.7%, P = 0.001, HR = 2.148, 95% CI, 1.384-3.333; 91.7% vs. 84.7% vs. 66.1%, P = 0.004, HR = 2.252, 95% CI = 1.296-3.912). The 5-year local relapse–free survival (LRFS) rates were not significantly different (95.8% vs. 86.0% vs. 81.8%, P = 0.137, HR = 1.975, 95% CI, 0.976-3.995). By multivariate analyses, the PT regression speed at the end of RT was the only independent prognostic factor of OS, FFS, and DMFS (P < 0.001, P = 0.001, and P = 0.004, respectively). The 5-year FFS rates for patients with CRPT during RT and CRPT only at the end of RT were 80.2% and 97.1%, respectively (P = 0.033). For patients with persistent PT at the end of RT, the 5-year LRFS rates of patients without and with boost irradiation were 87.1% and 84.6%, respectively (P = 0.812). Conclusions PT regression speed at the end of RT was an independent prognostic factor of OS, FFS, and DMFS in NPC patients. Immediate strengthening treatment may be provided to patients with poor

  18. Expression of mitochondrial transcription factor A in endometrial carcinomas: clinicopathologic correlations and prognostic significance.

    PubMed

    Toki, Naoyuki; Kagami, Seiji; Kurita, Tomoko; Kawagoe, Toshinori; Matsuura, Yusuke; Hachisuga, Toru; Matsuyama, Atsuji; Hashimoto, Hiroshi; Izumi, Hiroto; Kohno, Kimitoshi

    2010-04-01

    Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA. This study was conducted to elucidate the clinicopathologic and prognostic significance of mtTFA in patients with endometrial carcinoma. This study investigated the relationship between the immunohistochemical expression of mtTFA and various clinicopathological variables in 276 endometrial carcinomas, including 245 endometrioid adenocarcinomas and 31 nonendometrioid carcinomas (21 serous carcinomas and 10 clear cell adenocarcinomas). Both uni- and multivariate regression analyses were performed. The mtTFA labeling index of endometrioid adenocarcinomas ranged from 0% to 98%, with a median value of 32%, which was selected as the cut-off point for mtTFA expression. The mtTFA expression in endometrioid adenocarcinomas was significantly associated with the surgical stage, myometrial invasion, lymphovascular space invasion, cervical invasion, and lymph node metastasis. In contrast, no correlation between clinicopathologic variables and mtTFA expression was found in nonendometrioid carcinomas. Correlation analysis between mtTFA and p53 expression by using the Pearson test showed significant correlation in endometrioid adenocarcinomas (P = 0.007), but no significant correlation in nonendometrioid carcinomas (P = 0.947). A univariate survival analysis showed that the 10-year overall survival rate of the patients with mtTFA-positive endometrioid adenocarcinoma was significantly worse than that of patients with mtTFA-negative endometrioid adenocarcinoma (80.8% vs. 93.8%, P = 0.012). However, the multivariate analysis revealed that mtTFA expression in endometrioid adenocarcinomas was no independent prognostic factor. The positive mtTFA expression is a useful maker for progression of the tumors and the poor prognosis of the patients in endometrioid adenocarcinomas. PMID:20232213

  19. Prognostic significance of inflammatory factors expression by stroma from breast carcinomas.

    PubMed

    Fernandez-Garcia, Belen; Eiro, Noemi; Miranda, Maria-Angeles; Cid, Sandra; González, Luis O; Domínguez, Francisco; Vizoso, Francisco J

    2016-08-01

    The aim of this work was to evaluate the expression and clinical relevance of some cytokines in breast carcinomas. An immunohistochemical study using tissue arrays and specific antibodies against interleukin 1β (IL-1β), IL-6, IL-10, IL-17, interferon β (IFNβ) and nuclear factor kappa B (NFκB) was performed in 108 breast carcinomas. Most studied cytokines were mainly expressed by cancer cells but also by stromal cells as cancer-associated fibroblasts (CAFs) or mononuclear inflammatory cells (MICs). Global expression (score) of IL-1β and IL-17 was positively associated with histological grade; human epidermal growth factor receptor 2-positive tumors showed a higher global expression of IFNβ but a lower global expression of NFκB; and node-negative tumors showed a higher global expression of IL-6. High score of IL-6 was significantly associated with both longer relapse free-survival (RFS) and overall survival (OS). Moreover, the expression of IL-1β by each stromal cells (CAFs and MICs) was significantly associated with both longer RFS and OS, whereas the expression of IL-10 by these cells was significantly associated with both shorter RFS and OS. However, the combination of IL-1β, IL-6 and IL-10 expression by MICs reached an important association with prognosis and improved our previously reported prognostic signification based on the matrix metalloprotease 11 status by MICs. The combination of IL-1β, IL-6 and IL-10 expression by MICs was significant and independently associated with distant RFS in a multivariate analysis. Therefore, the combination of the expression of IL-1β, IL-6 and IL-10 may serve as promising biomarkers of MICs with prognostic significance, contributing to a better characterization of breast carcinomas microenvironment. PMID:27207649

  20. Hypoxia-inducible factor 1 alpha in high-risk breast cancer: an independent prognostic parameter?

    PubMed Central

    Gruber, Günther; Greiner, Richard H; Hlushchuk, Ruslan; Aebersold, Daniel M; Altermatt, Hans J; Berclaz, Gilles; Djonov, Valentin

    2004-01-01

    Background Hypoxia-inducible factor 1 alpha (hif-1α) furnishes tumor cells with the means of adapting to stress parameters like tumor hypoxia and promotes critical steps in tumor progression and aggressiveness. We investigated the role of hif-1α expression in patients with node-positive breast cancer. Methods Tumor samples from 77 patients were available for immunohistochemistry. The impact of hif-1α immunoreactivity on survival endpoints was determined by univariate and multivariate analyses, and correlations to clinicopathological characteristics were determined by cross-tabulations. Results hif-1α was expressed in 56% (n = 43/77) of the patients. Its expression correlated with progesterone receptor negativity (P = 0.002). The Kaplan–Meier curves revealed significantly shorter distant metastasis-free survival (DMFS) (P = 0.04, log-rank) and disease-free survival (DFS) (P = 0.04, log-rank) in patients with increased hif-1α expression. The difference in overall survival (OS) did not attain statistical significance (5-year OS, 66% without hif-1α expression and 55% with hif-1α expression; P = 0.21). The multivariate analysis failed to reveal an independent prognostic value for hif-1α expression in the whole patient group. The only significant parameter for all endpoints was the T stage (T3/T4 versus T1/T2: DMFS, relative risk = 3.16, P = 0.01; DFS, relative risk = 2.57, P = 0.03; OS, relative risk = 3.03, P = 0.03). Restricting the univariate and multivariate analyses to T1/T2 tumors, hif-1α expression was a significant parameter for DFS and DMFS. Conclusions hif-1α is expressed in the majority of patients with node-positive breast cancer. It can serve as a prognostic marker for an unfavorable outcome in those with T1/T2 tumors and positive axillary lymph nodes. PMID:15084243

  1. Kinesin family member 14: an independent prognostic marker and potential therapeutic target for ovarian cancer.

    PubMed

    Thériault, Brigitte L; Pajovic, Sanja; Bernardini, Marcus Q; Shaw, Patricia A; Gallie, Brenda L

    2012-04-15

    The novel oncogene KIF14 (kinesin family member 14) shows genomic gain and overexpression in many cancers including OvCa (ovarian cancer). We discovered that expression of the mitotic kinesin KIF14 is predictive of poor outcome in breast and lung cancers. We now determine the prognostic significance of KIF14 expression in primary OvCa tumors, and evaluate KIF14 action on OvCa cell tumorigenicity in vitro. Gene-specific multiplex PCR and real-time QPCR were used to measure KIF14 genomic (109 samples) and mRNA levels (122 samples) in OvCa tumors. Association of KIF14 with clinical variables was studied using Kaplan-Meier survival and Cox regression analyses. Cellular effects of KIF14 overexpression (stable transfection) and inhibition (stable shRNA knockdown) were studied by proliferation (cell counts), survival (Annexin V immunocytochemistry) and colony formation (soft-agar growth). KIF14 genomic gain (>2.6 copies) was present in 30% of serous OvCas, and KIF14 mRNA was elevated in 91% of tumors versus normal epithelium. High KIF14 in tumors independently predicted for worse outcome (p = 0.03) with loss of correlation with proliferation marker expression and increased rates of recurrence. Overexpression of KIF14 in OvCa cell lines increased proliferation and colony formation (p < 0.01), whereas KIF14 knockdown induced apoptosis and dramatically reduced colony formation (p < 0.05). Our findings indicate that KIF14 mRNA is an independent prognostic marker in serous OvCa. Dependence of OvCa cells on KIF14 for maintenance of in vitro colony formation suggests a role of KIF14 in promoting a tumorigenic phenotype, beyond its known role in proliferation. PMID:21618518

  2. Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia.

    PubMed

    Staffas, Anna; Kanduri, Meena; Hovland, Randi; Rosenquist, Richard; Ommen, Hans Beier; Abrahamsson, Jonas; Forestier, Erik; Jahnukainen, Kirsi; Jónsson, Ólafur G; Zeller, Bernward; Palle, Josefine; Lönnerholm, Gudmar; Hasle, Henrik; Palmqvist, Lars; Ehrencrona, Hans

    2011-11-24

    Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information. PMID:21967978

  3. Prognostic Significance and Functional Role of CEP57 in Prostate Cancer1

    PubMed Central

    Mang, Josef; Korzeniewski, Nina; Dietrich, Dimo; Sailer, Verena; Tolstov, Yanis; Searcy, Sam; von Hardenberg, Jost; Perner, Sven; Kristiansen, Glen; Marx, Alexander; Roth, Wilfried; Herpel, Esther; Grüllich, Carsten; Popeneciu, Valentin; Pahernik, Sascha; Hadaschik, Boris; Hohenfellner, Markus; Duensing, Stefan

    2015-01-01

    We have recently shown that centrosomal protein 57 (CEP57) is overexpressed in a subset of human prostate cancers. CEP57 is involved in intracellular transport processes, and its overexpression causes mitotic defects as well as abnormal microtubule nucleation and bundling. In the present study, we further characterized the prognostic and functional role of CEP57 in prostate cancer. Unexpectedly, we found that high CEP57 expression is an independent prognostic factor for a more favorable biochemical recurrence-free survival in two large patient cohorts. To reconcile this finding with the ability of CEP57 to cause cell division errors and thus potentially promote malignant progression, we hypothesized that alterations of microtubule-associated transport processes, in particular nuclear translocation of the androgen receptor (AR), may play a role in our finding. However, CEP57 overexpression and microtubule bundling had, surprisingly, no effect on the nuclear translocation of the AR. Instead, we found a significant increase of cells with disarranged microtubules and a cellular morphology suggestive of a cytokinesis defect. Because mitotic dysfunction leads to a reduced daughter cell formation, it can explain the survival benefit of patients with increased CEP57 expression. In contrast, we show that a reduced expression of CEP57 is associated with malignant growth and metastasis. Taken together, our findings underscore that high CEP57 expression is associated with mitotic impairment and less aggressive tumor behavior. Because the CEP57-induced microtubule stabilization had no detectable effect on AR nuclear translocation, our results furthermore suggest that microtubule-targeting therapeutics used in advanced prostate cancer such as docetaxel may have modes of action that are at least in part independent of AR transport inhibition. PMID:26692530

  4. Nuclear PARP1 expression and its prognostic significance in breast cancer patients.

    PubMed

    Mazzotta, Annalisa; Partipilo, Giulia; De Summa, Simona; Giotta, Francesco; Simone, Giovanni; Mangia, Anita

    2016-05-01

    Poly(adenosine diphosphate [ADP]-ribose) polymerase 1 (PARP1) plays important roles in DNA damage response pathways and is often overexpressed in various human tumors. Currently, the use of PARP inhibitors for breast cancer (BC) therapy is the subject of debate, and there is an urgent need to understand much the expression and prognostic role of the PARP1 protein. The aim was to investigate the clinicopathological and prognostic significance of PARP1 in BC patients. The PARP1 and breast cancer susceptibility gene 1 (BRCA1) protein expressions were evaluated in 114 BCs by immunohistochemistry. Disease-free survival (DFS) and overall survival (OS) were determined based on the Kaplan-Meier method. Our results showed that nuclear PARP1 expression was significantly associated with peritumoral vascular invasion (P = 0.046), chemotherapeutic treatment (P = 0.026), oestrogen receptor (ER; P = 0.013), human epidermal growth factor receptor 2 (HER2; P = 0.003) and BRCA1 (P < 0.001) expression. Survival analyses showed a significant association with clinical outcome in the subgroup of ER-negative patients (P = 0.017 for DFS and P = 0.048 for OS) and in the subgroup of patients treated with chemotherapeutic agents (P = 0.042 for DFS and P = 0.046 for OS). A significant correlation was also found for DFS in patients characterized by tumors without peritumoral vascular invasion (P = 0.022). More importantly, multivariate analyses revealed that high nuclear PARP1 expression was associated with decreased DFS (P = 0.012) and OS (P = 0.026). In conclusion, PARP1 expression may be used as an independent prognostic factor in BC patients. In addition, this study demonstrated that high PARP1 expression may represent a marker of poorer prognosis both for patients with worse clinical outcome and in less aggressive clinical conditions. PMID:26614429

  5. Prognostic significance of β2-adrenergic receptor expression in malignant melanoma.

    PubMed

    Shimizu, Akira; Kaira, Kyoichi; Mori, Keita; Kato, Madoka; Shimizu, Kimihiro; Yasuda, Masahito; Takahashi, Ayumi; Oyama, Tetsunari; Asao, Takayuki; Ishikawa, Osamu

    2016-05-01

    Recent studies cite β2-adrenergic receptor (β2AR) antagonists as novel therapeutic agents for melanoma, as they may reduce the disease progression. The β2AR has shown to be expressed in malignant melanoma. However, it remains unclear whether the β2AR expression has a clinical and pathological significance in patients with cutaneous malignant melanoma. We herein conducted a clinicopathological study to investigate the protein expression of β2AR in malignant melanoma of the skin and its prognostic significance. One hundred thirty-three patients with surgically resected cutaneous malignant melanoma were evaluated. Tumor sections were stained by immunohistochemistry for β2AR, Ki-67, the microvessel density (MVD) determined by CD34, and p53. β2AR was highly expressed in 44.4 % (59 out of 133) of the patients. The expression of β2AR was significantly associated with the tumor thickness, ulceration, T factor, N factor, disease stage, tumor size, cell proliferation (Ki-67), and MVD (CD34). Using Spearman's rank test, the β2AR expression was correlated with Ki-67 (r = 0.278; 95 % CI, 0.108 to 0.432; P = 0.001), CD34 (r = 0.445; 95 %CI, 0.293 to 0.575; P < 0.001), and the tumor size (r = 0.226; 95 % CI, 0.053 to 0.386; P = 0.008). Using a univariate analysis, the tumor thickness, ulceration, disease stage, β2AR, Ki-67, and CD34 had a significant relationship with the overall and progression-free survivals. A multivariable analysis confirmed that β2AR was an independent prognostic factor for predicting a poor overall survival (HR 1.730; 95 % CI 1.221-2.515) and progression-free survival (HR 1.576; 95 % CI 1.176-2.143) of malignant melanoma of the skin. β2AR can serve as a promising prognostic factor for predicting a worse outcome after surgical treatment and may play an important role in the development and aggressiveness of malignant melanoma. PMID:26596834

  6. TPX2 in human clear cell renal carcinoma: Expression, function and prognostic significance

    PubMed Central

    CHEN, QI; CAO, BIN; NAN, NING; WANG, YU; ZHAI, XU; LI, YOUFANG; CHONG, TIE

    2016-01-01

    Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein. TPX2 is considered to be an important gene in tumorigenesis; however, the particular function of TPX2 in the development of human renal cell carcinoma (RCC) is unknown. In the present study, the expression, function and prognostic significance of TPX2 in human RCC was analyzed. A total of 286 tissue samples from patients with RCC who had undergone nephrectomies were utilized. Subsequently, the expression of TPX2 protein was investigated using immunohistochemistry and western blotting, and TPX2 mRNA expression was examined using reverse transcription-quantitative polymerase chain reaction. To establish the effect of TPX2 on the proliferation and invasion of the RCC cells, TPX2 expression was increased by stable transfection with a TPX2 vector and TPX2 expression was decreased using small interfering RNA. Proliferation of the RCC cells was analyzed using a WST-1 assay and an animal xenograft model with BALB/c nude mice, whilst invasion of the RCC cells was examined using a Matrigel-coated invasion chamber. It was demonstrated that TPX2 expression was significantly higher in the RCC tissues compared with normal kidney tissues (P<0.05). Furthermore, TPX2 expression was associated with tumor size, histological grade and tumor stage (P<0.05), and was observed to markedly increase the proliferation and invasion of the RCC cells. It may be concluded that the expression of TPX2 is significantly upregulated in RCC tissue, subsequently increasing the proliferative and invasive ability of RCC cells. Therefore, the protein may serve as a therapeutic target and independent prognostic factor in the treatment of human RCC. PMID:27123144

  7. Prognostic Significance of Carbonic Anhydrase IX Expression in Cancer Patients: A Meta-Analysis

    PubMed Central

    van Kuijk, Simon J. A.; Yaromina, Ala; Houben, Ruud; Niemans, Raymon; Lambin, Philippe; Dubois, Ludwig J.

    2016-01-01

    Hypoxia is a characteristic of many solid tumors and an adverse prognostic factor for treatment outcome. Hypoxia increases the expression of carbonic anhydrase IX (CAIX), an enzyme that is predominantly found on tumor cells and is involved in maintaining the cellular pH balance. Many clinical studies investigated the prognostic value of CAIX expression, but most have been inconclusive, partly due to small numbers of patients included. The present meta-analysis was therefore performed utilizing the results of all clinical studies to determine the prognostic value of CAIX expression in solid tumors. Renal cell carcinoma was excluded from this meta-analysis due to an alternative mechanism of upregulation. 958 papers were identified from a literature search performed in PubMed and Embase. These papers were independently evaluated by two reviewers and 147 studies were included in the analysis. The meta-analysis revealed strong significant associations between CAIX expression and all endpoints: overall survival [hazard ratio (HR) = 1.76, 95% confidence interval (95%CI) 1.58–1.98], disease-free survival (HR = 1.87, 95%CI 1.62–2.16), locoregional control (HR = 1.54, 95%CI 1.22–1.93), disease-specific survival (HR = 1.78, 95%CI 1.41–2.25), metastasis-free survival (HR = 1.82, 95%CI 1.33–2.50), and progression-free survival (HR = 1.58, 95%CI 1.27–1.96). Subgroup analyses revealed similar associations in the majority of tumor sites and types. In conclusion, these results show that patients having tumors with high CAIX expression have higher risk of locoregional failure, disease progression, and higher risk to develop metastases, independent of tumor type or site. The results of this meta-analysis further support the development of a clinical test to determine patient prognosis based on CAIX expression and may have important implications for the development of new treatment strategies. PMID:27066453

  8. The ABO Blood Group is an Independent Prognostic Factor in Patients With Resected Non-small Cell Lung Cancer

    PubMed Central

    Fukumoto, Koichi; Taniguchi, Tetsuo; Usami, Noriyasu; Kawaguchi, Koji; Fukui, Takayuki; Ishiguro, Futoshi; Nakamura, Shota; Yokoi, Kohei

    2015-01-01

    Background The ABO blood group is reported to be associated with the incidence and patient survival for several types of malignancies. We conducted a retrospective study to evaluate the prognostic significance of the ABO blood group in patients with resected non-small cell lung cancer (NSCLC). Methods A total of 333 patients (218 men and 115 women) with resected NSCLC were included in this study. In addition to age, sex, smoking status, preoperative serum carcinoembryonic antigen (CEA) level, operative procedure, histology of tumors, pathological stage (p-stage), and adjuvant therapy, the association between the ABO blood group and survival was explored. Results The 5-year overall and disease-free survival rates were 83.0% and 71.6% for blood group O, 67.2% and 62.3% for blood group A, 68.8% and 68.8% for blood group B and 69.2% and 65.3% for blood group AB, respectively. A multivariate analysis for overall survival showed the ABO blood group (group A vs. group O: HR 2.47, group AB vs. group O: HR 3.62) to be an independent significant prognostic factor, in addition to age, sex, smoking status, p-stage, and serum CEA level. A multivariate analysis for disease-free survival also showed the ABO blood group to be an independent significant prognostic factor. Conclusions The ABO blood group is an independent prognostic factor in patients with resected NSCLC. Studies of other larger cohorts are therefore needed to confirm the relationship between the ABO blood group and the prognosis among patients with resected NSCLC. PMID:25483106

  9. Sarcopenia is an independent prognostic factor in male patients with diffuse large B-cell lymphoma.

    PubMed

    Nakamura, Nobuhiko; Hara, Takeshi; Shibata, Yuhei; Matsumoto, Takuro; Nakamura, Hiroshi; Ninomiya, Soranobu; Kito, Yusuke; Kitagawa, Junichi; Kanemura, Nobuhiro; Goto, Naoe; Shiraki, Makoto; Miyazaki, Tatsuhiko; Takeuchi, Tamotsu; Shimizu, Masahito; Tsurumi, Hisashi

    2015-12-01

    Sarcopenia reportedly predicts poor outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL). However, because previous studies only involved elderly patients, it is difficult to generalize these results to all patients with DLBCL. We retrospectively analyzed 207 patients with DLBCL who received the R-CHOP or R-THP-COP regimen between June 2004 and May 2014. Sarcopenia was measured by the analysis of CT images at the L3 level before treatment. The surface of muscular tissues was selected according to the CT Hounsfield unit. This value was normalized for stature in order to calculate the L3 skeletal muscle index (L3 SMI, cm(2)/m(2)). Median age at diagnosis in the 121 males and 86 females was 67 years (range, 19-86 years). The sex-specific cutoffs for the L3 SMI were determined by receiver operator curve (ROC) analysis. Sarcopenic patients were older than non-sarcopenic patients, with a median age of 70 and 65 years, respectively (p < 0.001). Other International Prognostic Index factors were not significantly different when comparing sarcopenic and non-sarcopenic patients. With a median follow-up of 50.4 months, the 3-year overall survival (OS) was 70 % in the sarcopenic group and 85 % in the non-sarcopenic group (p = 0.0260). In a subgroup analysis by gender, there was a significant difference in the OS when comparing sarcopenic and non-sarcopenic patients in males but not in females (p = 0.0003, p = 0.4440, respectively). Sarcopenia is an independent prognostic factor in male patients with DLBCL. PMID:26385388

  10. Prognostic Significance of Nuclear β-Catenin Expression in Patients with Colorectal Cancer from Iran

    PubMed Central

    Nazemalhosseini Mojarad, Ehsan; Kashfi, Seyed Mohammad Hossein; Mirtalebi, Hanieh; Almasi, Shohre; Chaleshi, Vahid; Kishani Farahani, Roya; Tarban, Peyman; Molaei, Mahsa; Zali, Mohammad Reza; J.K. Kuppen, Peter

    2015-01-01

    Background: Beta catenin plays a key role in cancer tumorigenesis. However, its prognostic significance in patients with colorectal cancer (CRC) remains controversial. It has been demonstrated that 90% of all tumors have a mutation in individual components of multiple oncogenes in Wnt/β-catenin pathway. Accumulation of nuclear β-catenin in cytoplasm leads to uncontrolled cell proliferation. Thus, nuclear β-catenin accumulation may be a valuable biomarker associated with invasion, metastasis and poor prognosis of CRC. Objectives: In this study the prognostic value of beta catenin expression in 165 Iranian CRC patients was evaluated. Patients and Methods: In this cross sectional retrospective study immunohistochemistry analyses of formalin-fixed paraffin-embedded (FFPE) tumor tissues were performed to characterize the expression of nuclear β-catenin in a series of 165 Iranian patients with colorectal carcinoma. Heat-induced antigen retrieval using the microwave method was applied for all staining procedures. Staining was scored independently by two observers, and a high level of concordance (90%) was achieved. Statistical analysis was done using the SPSS software for Windows, version 13.0.0 (SPSS Inc., Chicago, IL). Two-tailed P < 0.05 was considered statistically significant. Results: The patients consisted of 85 males and 80 females. Eighty-eight patients had primary tumor of the rectum and sigmoid, while 77 patients had primary tumor of the colon. The mean period of follow-up was 47.2 ± 10 months and the median period of follow-up was 38 months (range 6 - 58) for each patient. Of 165 tumors, 32 tumors (19.39 %) showed expression of β-catenin and 133 (80.6 %) were negative for β-catenin expression. Based on our findings the distribution of Microsatellite Instability (MSI) status differed between patients with nuclear β-catenin positive and negative tumors and this difference was significant (P = 0.001). Patients with nuclear β-catenin positive expression

  11. Coexpression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

    PubMed Central

    Jia, Wei; Wang, Wei; Ji, Chu-shu; Niu, Jun-yang; Lv, Ya-jing; Zhou, Hang-cheng; Hu, Bing

    2016-01-01

    Background Both periostin (PN) and epidermal growth factor receptor (EGFR) can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC) still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. Patients and methods In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ2 or Kruskal–Wallis method. Spearman’s rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan–Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS) and overall survival (OS). Results The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044), differentiation grade (P=0.003), venous invasion (P=0.010), invasion depth (P=0.007), lymphatic metastasis (P=0.000), and tumor stage (P=0.000). The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000), invasion depth (P=0.022), and tumor stage (P=0.000). Kaplan–Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000) and DFS (P=0.000), which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS in the ESCC patients (P<0.05). Moreover, the risk of death for the ESCC patients with low expression of two biomarkers and high expression of single biomarker was 0.243 times (P=0.000) and 0.503 times (P=0.030), respectively, than that for

  12. Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.

    PubMed

    Laurinavicius, Arvydas; Plancoulaine, Benoit; Rasmusson, Allan; Besusparis, Justinas; Augulis, Renaldas; Meskauskas, Raimundas; Herlin, Paulette; Laurinaviciene, Aida; Abdelhadi Muftah, Abir A; Miligy, Islam; Aleskandarany, Mohammed; Rakha, Emad A; Green, Andrew R; Ellis, Ian O

    2016-04-01

    Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity. PMID:26818835

  13. Immunohistologic detection of estrogen receptor alpha in canine mammary tumors: clinical and pathologic associations and prognostic significance.

    PubMed

    Nieto, A; Peña, L; Pérez-Alenza, M D; Sánchez, M A; Flores, J M; Castaño, M

    2000-05-01

    Eighty-nine canine mammary tumors and dysplasias of 66 bitches were investigated to determine the immunohistochemical expression of classical estrogen receptor (ER-alpha) and its clinical and pathologic associations and prognostic value. A complete clinical examination was performed and reproductive history was evaluated. After surgery, all animals were followed-up for 18 months, with clinical examinations every 3-4 months. ER-alpha expression was higher in tumors of genitally intact and young bitches (P < 0.01, P < 0.01) and in animals with regular estrous periods (P = 0.03). Malignant tumors of the bitches with a previous clinical history of pseudopregnancy expressed significantly more ER-alpha (P = 0.04). Immunoexpression of ER-alpha decreased significantly with tumor size (P = 0.05) and skin ulceration (P = 0.01). Low levels of ER-alpha were significantly associated with lymph node involvement (P < 0.01). Malignant tumors had lower ER-alpha expression than did benign tumors (P < 0.01). Proliferation index measured by proliferating cell nuclear antigen immunostaining was inversely correlated with ER-alpha scores (P = 0.05) in all tumors. Low ER-alpha levels in primary malignant tumors were significantly associated with the occurrence of metastases in the follow-up (P = 0.03). Multivariate analyses were performed to determine the prognostic significance of some follow-up variables. ER-alpha value, Ki-67 index, and age were independent factors that could predict disease-free survival. Lymph node status, age, and ER-alpha index were independent prognostic factors for the overall survival. The immunohistochemical detection of ER-alpha in canine mammary tumors is a simple technique with prognostic value that could be useful in selecting appropriate hormonal therapy. PMID:10810988

  14. Prognostic significance of survivin expression in renal cell cancer and its correlation with radioresistance.

    PubMed

    Lei, Yu; Geng, Zhang; Guo-Jun, Wu; He, Wang; Jian-Lin, Yuan

    2010-11-01

    Survivin, an important inhibitor of apoptosis, has been found to play an important role in the initiation, progression, and chemoradioresistance of human malignancies. Previously, we have reported that upregulation of survivin in oral squamous cell carcinoma correlates with poor prognosis and chemoresistance. The aim of this study was to assess prognostic significance of survivin protein expression in RCC and analyze its correlation with radiosensitivity of RCC cells. RT-PCR and Western blot assays were performed to detect survivin mRNA and protein expression in normal human kidney epithelial cell line (HKEC) or RCC cell lines. The expression of survivin mRNA in RCC and corresponding nontumor kidney tissues was also detected by RT-PCR. Immunohistochemistry was performed to determine survivin protein expression in 75 cases of RCC tissue samples. Moreover, the association of survivin protein expression with clinicopathogical factors and prognosis of RCC patients was statistically analyzed. Small interfering RNA was used to knockdown the endogenous survivin expression in RCC cell line (ACHN) and evaluate the effects of survivin knockdown on proliferation, apoptosis, and radiosensitivity of RCC cell line. RCC cells showed sufficient expression of survivin mRNA and protein, but the expression of survivin gene was not detected in normal HKEC. Moreover, the expression level of survivin mRNA in RCC tissues was significantly higher than that in corresponding nontumor kidney tissues. The immunostaining of survivin protein was mainly located in cytoplasm of RCC tumor cells. Tumor pathological stage (P = 0.028), grade (P = 0.004), and lymph node metastasis (P = 0.017) of RCC patients were significantly correlated with survivin protein expression. In addition, patients with high survivin levels had a significantly shorter overall survival than those with low levels (P < 0.001), and the expression of survivin protein was an independent prognostic factor for RCC patients (P = 0

  15. Prognostic significance of Ki-67 antigen expression in extranodal natural killer/T-cell lymphoma, nasal type.

    PubMed

    Jiang, Li; Li, Pengfei; Wang, Hua; Liu, Jun; Zhang, Xinke; Qiu, Huijuan; Zhang, Bei

    2014-10-01

    Extranodal natural killer (NK)/T-cell lymphoma, nasal-type (ENKTL) is a clinically heterogeneous disease with poor prognosis and requires risk stratification in affected patients. Recent studies have shown that Ki-67 may serve as a prognostic marker in certain types of lymphoma. We analyzed Ki-67 expression and its correlation with prognosis in 182 patients with ENKTL from January 2002 to June 2013. The patients were classified into two groups through a median value: low (<60%) versus high Ki-67 (≥60%). High Ki-67 expression was more common in patients with B symptoms (p=0.02), bulky disease (p=0.001), and extraupper aerodigestive tract NK/T-cell lymphoma (p=0.001). High Ki-67 expression was significantly associated with poor overall survival (p<0.0001) and progression-free survival (p<0.0001). For patients with low-risk IPI or KPI, Ki-67 at diagnosis could contribute to distinguish patients with favorable outcomes from those with poor outcomes. The results of multivariate analysis showed that the high Ki-67 expression is an independent prognostic factor for overall survival and progression-free survival. (OS, p=0.001; PFS, p=0.003). Our data showed that Ki-67 is an effective prognostic indicator of survival in ENKTL patients. This prognostic index may be helpful in identifying high-risk patients with ENKTL. PMID:25204411

  16. Prognostic significance of phosphorylated RON in esophageal squamous cell carcinoma.

    PubMed

    Hui, Marco K C; Lai, Kenneth K Y; Chan, Kwok Wah; Luk, John M; Lee, Nikki P; Chung, Yvonne; Cheung, Leo C; Srivastava, Gopesh; Tsao, Sai Wah; Tang, Johnny C; Law, Simon

    2012-09-01

    Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer. RON is a transmembrane receptor overexpressed in various cancers; however, the clinical significance of its phosphorylated form (pRON) is not fully deciphered. This report is the first to investigate the expression and clinical significance of pRON in human ESCC. Quantitative polymerase chain reaction revealed an up-regulation of RON mRNA in 70% (7/10) of ESCC tissues when compared to the adjacent nontumor tissues. An overexpression of pRON protein was found in most of the ESCC cell lines studied (4/5) when compared to two non-neoplastic esophageal epithelial cells using immunoblot. In 64 ESCC tissues, pRON was localized at the cell membrane, cytoplasm and nucleus in 15 (23.4%), 63 (98.4%) and 61 (95.3%) cases using immunohistochemistry. Patients having high expression of cytoplasmic pRON significantly associated with shorter median survival when compared to those with low expression (25.41 months vs. 14.43 months), suggesting cytoplasmic pRON as a potential marker for poor prognosis in ESCC patients. PMID:22086736

  17. Prognostic Significance of Polymer Coatings in Zotarolimus-Eluting Stents.

    PubMed

    Iqbal, M Bilal; Nadra, Imad J; Din, Jehangir N; Hendry, Cara; Ding, Lillian; Fung, Anthony; Aymong, Eve; Chan, Albert W; Hodge, Steven; Robinson, Simon D; Della Siega, Anthony

    2016-03-01

    Polymer coatings on drug-eluting stents (DES) serve as a vehicle for delivery of antirestenotic drugs. Whether they influence outcomes for contemporary DES is unknown. The evolution of polymer coatings for zotarolimus-eluting stents (ZES) provides a natural experiment that facilitates such analysis. The Resolute ZES (R-ZES) uses the same antirestenotic drug as the Endeavor ZES (E-ZES) but has a more biocompatible polymer with enhanced drug release kinetics. However, there are limited data on the real-world comparative efficacy of R-ZES and the preceding E-ZES. Thus, we analyzed 17,643 patients who received either E-ZES or R-ZES from 2008 to 2014 from the British Columbia Cardiac Registry. A total of 9,869 patients (56%) received E-ZES and 7,774 patients (44%) received R-ZES. Compared with E-ZES, R-ZES was associated with lower 2-year mortality (4.1% vs 6.4%, p <0.001) and 2-year target vessel revascularization (TVR; 6.8% vs 10.7%, p <0.001). R-ZES use was an independent predictor of lower mortality rate and TVR. This was confirmed in propensity-matched analyses for 2-year mortality (hazard ratio [HR] 0.59, 95% CI 0.49 to 0.71, p <0.001) and 2-year TVR (HR 0.86, 95% CI 0.75 to 0.98, p = 0.032). Instrumental variable analyses demonstrated R-ZES to be associated with lower 2-year mortality (Δ = -2.2%, 95% CI -4.3% to -0.2%, p = 0.032) and 2-year TVR (Δ = -3.3% to 95% CI -6.1% to -0.7%, p = 0.015). Acknowledging the limitations of observational analyses, this study has shown that R-ZES was associated with lower long-term TVR and mortality. These data are reassuring for the newer R-ZES and demonstrate how polymer coatings may influence the clinical performance of DES with wider implications for future DES development and design. PMID:26796194

  18. Clinical Significance of the Prognostic Nutritional Index for Predicting Short- and Long-Term Surgical Outcomes After Gastrectomy

    PubMed Central

    Lee, Jee Youn; Kim, Hyoung-Il; Kim, You-Na; Hong, Jung Hwa; Alshomimi, Saeed; An, Ji Yeong; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong-Bai

    2016-01-01

    Abstract To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy. Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer. We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups. Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212–1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760–10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221–1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985–1.325, P = 0.078). PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence. PMID:27149460

  19. Prognostic Significance of Frontal QRS-T Angle in Patients with Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Li, Sheng-Na; Zhang, Xin-Lin; Cai, Guo-Long; Lin, Ruo-Wei; Jiang, He; Chen, Jian-Zhou; Xu, Biao; Huang, Wei

    2016-01-01

    Background: Current risk stratification of idiopathic dilated cardiomyopathy (IDC) lacks sufficient sensitivity and specificity. The objective of this study was to investigate the predictive role of frontal QRS-T angles in IDC. Methods: A prospective study with 509 IDC patients was performed from February 2008 to December 2013 in the Affiliated Drum Tower Hospital, Nanjing University School of Medicine. Baseline values and changes in QRS-T angles were recorded. Follow-up was conducted every 6 months. Analyses by Cox Proportional Hazards model were performed to evaluate the association between QRS-T angle and outcomes. The primary outcome of interest was all-cause mortality. Results: During a median follow-up of 34 months, 90 of 316 patients with QRS-T angles >90° died compared to 31 of 193 patients with QRS-T angles ≤90° (hazard ratio [HR] =2.4, P < 0.001). Cardiac death was more prevalent in patients with a wide QRS-T angle (HR = 2.4, P < 0.001), similar to heart failure rehospitalization (HR = 2.5, P < 0.001). After adjustment for potential prognostic factors, the QRS-T angle was independently associated with all-cause mortality (HR = 2.5, P < 0.05), cardiac mortality (HR = 1.9, P < 0. 05), and heart failure rehospitalization (HR = 2.3, P < 0.01). Optimized therapy significantly narrowed the frontal QRS-T angle (100.9 ± 53.4° vs. 107.2 ± 54.4°, P < 0.001). The frontal QRS-T angle correlated well with established risk factors, such as left ventricular ejection fraction, brain natriuretic peptide, and New York Heart Association functional class. Conclusions: The frontal QRS-T angle is a powerful predictor of all-cause mortality, cardiac mortality, and worsening heart failure in IDC patients, independent of well-established prognostic factors. Optimized therapy significantly narrows the QRS-T angle, which might be an indicator of medication compliance, but this requires further investigation. PMID:27503013

  20. Role and prognostic significance of the epithelial-mesenchymal transition factor ZEB2 in ovarian cancer

    PubMed Central

    Prislei, Silvia; Martinelli, Enrica; Zannoni, Gian Franco; Petrillo, Marco; Filippetti, Flavia; Mariani, Marisa; Mozzetti, Simona; Raspaglio, Giuseppina; Scambia, Giovanni; Ferlini, Cristiano

    2015-01-01

    ZEB2 is a key factor in epithelial-mesenchymal transition (EMT), a program controlling cell migration in embryonic development and adult tissue homeostasis. We demonstrated a role of ZEB2 in migration and anchorage-independent cell growth in ovarian cancer, as shown by ZEB2 silencing. We found that the RNA-binding protein HuR bound the 3′UTR of ZEB2 mRNA, acting as a positive regulator of ZEB2 protein expression. In Hey ovarian cell line, HuR silencing decreased ZEB2 and ZEB1 nuclear expression and impaired migration. In hypoglycemic conditions ZEB2 expression decreased, along with ZEB1, vimentin and cytoplasmic HuR, and a reduced cellular migration ability was observed. Analysis of ZEB2 and HuR expression in ovarian cancers revealed that nuclear ZEB2 is localized in tumor leading edge and co-localizes with cytoplasmic HuR. In a series of 143 ovarian cancer patients high expression of ZEB2 mRNA significantly correlated with a poor prognosis in term of both overall survival and progression- free survival. Moreover, at immunohistochemical evaluation, we found that prognostic significance of ZEB2 protein relies on its nuclear expression and co-localization with cytoplasmic HuR. In conclusion our findings indicated that nuclear ZEB2 may enhance progression of EMT transition and acquisition of an aggressive phenotype in ovarian cancer. PMID:26136338

  1. Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma.

    PubMed

    Saito, Yoichi; Ohnishi, Koji; Miyashita, Azusa; Nakahara, Satoshi; Fujiwara, Yukio; Horlad, Hasita; Motoshima, Takanobu; Fukushima, Satoshi; Jinnin, Masatoshi; Ihn, Hironobu; Takeya, Motohiro; Komohara, Yoshihiro

    2015-12-01

    CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on macrophages, including lymph node sinus macrophages. Animal studies suggest that CD169(+) macrophages in lymph nodes have properties in preventing cancers. In order to determine the significance of CD169(+) macrophages in patients with malignant melanoma, we evaluated tissue samples from 93 patients to investigate CD169 expression in regional lymph nodes (RLN) and determine the relationship of this expression with overall survival and various clinicopathologic factors. Higher densities of CD169(+) cells were significantly associated with longer overall survival (P = 0.001). A multivariate analysis showed that the density of CD169(+) cells was an independent prognostic factor, with higher densities correlating with higher density of CD8(+) cytotoxic T cells within tumor sites. High CD169 expression in macrophages could be stimulated by IFNα in vitro, and in RLNs, IFNα-producing macrophages and CD303(+) plasmacytoid dendritic cells were identified surrounding CD169(+) macrophages. These data suggest that IFNα-stimulated CD169(+) macrophages in RLNs are closely involved in T-cell-mediated antitumor immunity and may be a useful marker for assessing the clinical prognosis and monitoring antitumor immunity in patients with malignant melanoma. PMID:26297710

  2. Clinical and prognostic significance of serum transforming growth factor-beta1 levels in patients with pancreatic ductal adenocarcinoma

    PubMed Central

    Zhao, J.; Liang, Y.; Yin, Q.; Liu, S.; Wang, Q.; Tang, Y.; Cao, C.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate of 5%. Biomarkers for the early detection of pancreatic cancer are urgently needed. Transforming growth factor-beta1 (TGF-β1) is elevated in the tissues and plasma of patients with PDAC. However, no studies systemically report prognostic significance of plasma TGF-β1 levels in PDAC. In the present study, we assessed the prognostic significance of serum TGF-β levels in patients with PDAC. TGF-β levels were determined in serum from 146 PDAC patients, and 58 patients with benign pancreatic conditions. Regression models were used to correlate TGF-β levels to gender, age, stage, class, and metastasis. Survival analyses were performed using multivariate Cox models. Serum levels of TGF-β1 distinguished PDAC from benign pancreatic conditions (P<0.001) and healthy control subjects (P<0.001). Serum levels of TGF-β also distinguished tumor stage (P=0.002) and lymph node metastasis (P=0.001). High serum levels of TGF-β1 were significantly correlated with reduced patient survival. Multivariate analysis revealed that TGF-β1, lymph node metastasis and tumor stage were independent factors for PDAC survival. Our results indicate that serum TGF-β1 may be used as a potential prognostic marker for PDAC. PMID:27464025

  3. Prognostic significance of Helix pomatia lectin and c-erbB-2 oncoprotein in human breast cancer.

    PubMed Central

    Thomas, M.; Noguchi, M.; Fonseca, L.; Kitagawa, H.; Kinoshita, K.; Miyazaki, I.

    1993-01-01

    We investigated the prognostic significance of Helix pomatia lectin (HPA) staining on disease-free and overall survival in 120 primary breast carcinomas. HPA staining was present in 58 (48%) of these carcinomas. It was significantly associated with axillary lymph node metastases (P < 0.001) and c-erbB-2 expression (P < 0.01). A univariate study revealed that disease-free and overall survival were significantly correlated with clinical stage, tumour size, axillary lymph node metastases. HPA staining and c-erbB-2 expression. In a multivariate study, all previous prognostic indicators except HPA staining and c-erbB-2 expression were independent factors. However, stratifying the patients on the basis of HPA and c-erbB-2 status suggested that HPA +/c-erbB-2+ status was predictive of a higher incidence of axillary lymph node metastases (P = 0.000001) and a poorer overall (P < 0.0002) and a shorter disease-free (P < 0.000006) survival when compared with the other subgroups, although this combination did not provide any additional prognostic information for overall (P = 0.3544) or disease-free (P = 0.7152) survival by a multivariate analysis. For patients in whom axillary lymph node dissection has not been performed, therefore, HPA and c-erbB-2 status seems to be a powerful tool to discriminate subpopulations with a high recurrence risk and shorter survival who should undergo more aggressive therapy. PMID:8102537

  4. Ventricular arrhythmias in dilated cardiomyopathy as an independent prognostic hallmark. Italian Multicenter Cardiomyopathy Study (SPIC) Group.

    PubMed

    De Maria, R; Gavazzi, A; Caroli, A; Ometto, R; Biagini, A; Camerini, F

    1992-06-01

    Prevalence and characteristics of ventricular arrhythmias (VA) on Holter monitoring were evaluated in 218 patients with invasively documented idiopathic dilated cardiomyopathy to clarify their relation to pump dysfunction, and their prognostic role. VA were observed in 205 patients (94%) and were high grade (ventricular pairs or tachycardia) in 130 (60%). No simple or multiform ventricular premature complexes were present in 88 patients (group 1; 41%), ventricular pairs in 63 (group 2; 32%), and ventricular tachycardia in 67 (group 3; 27%). Only echocardiographic right ventricular dimensions (p less than 0.05) and prevalence of VA during effort (8% in group 1, 15% in group 2, and 14% in group 3; p = 0.0005) differed significantly between groups. VA severity, and number of ventricular premature beats and tachycardia episodes were not correlated to right/left ventricular dimensions and pump function indexes. During a mean follow-up of 29 +/- 16 months, 27 patients died from cardiac events, and 16 received transplants. Three-year survival probability was lower in groups 2 (0.82) and 3 (0.81) than in group 1 (0.94). By Cox multivariate analysis, VA severity (p less than 0.01) was a major independent predictor of prognosis after markers of ventricular dysfunction such as left ventricular ejection fraction (p less than 0.001) and stroke work index (p less than 0.001). PMID:1590236

  5. MALDI-imaging reveals thymosin beta-4 as an independent prognostic marker for colorectal cancer

    PubMed Central

    Gemoll, Timo; Strohkamp, Sarah; Schillo, Katharina; Thorns, Christoph; Habermann, Jens K.

    2015-01-01

    DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for direct analysis of multiple proteins in tissue sections while maintaining the cellular and molecular integrity. We compared diploid and aneuploid colon cancer tissues against normal mucosa of the colon by means of IMS. DNA image cytometry determined the ploidy status of tissue samples that were subsequently subjected to MALDI-IMS. After obtaining protein profiles through direct analysis of tissue sections, a discovery and independent validation set were used to predict ploidy status by applying proteomic classification algorithms [Supervised Neural Network (SNN) and Receiver Operating Characteristic (ROC)]. Five peaks (m/z 2,395 and 4,977 for diploid vs. aneuploid comparison as well as m/z 3,376, 6,663, and 8,581 for normal mucosa vs. carcinoma comparison) were significant in both SNN and ROC analysis. Among these, m/z 4,977 was identified as thymosin beta 4 (Tβ-4). Tβ-4 was subsequently validated in clinical samples using a tissue microarray to predict overall survival in colon cancer patients. PMID:26556858

  6. Echocardiography and pulmonary embolism severity index have independent prognostic roles in pulmonary embolism.

    PubMed

    Sanchez, Olivier; Trinquart, Ludovic; Planquette, Benjamin; Couturaud, Francis; Verschuren, Franck; Caille, Vincent; Meneveau, Nicolas; Pacouret, Gérard; Roy, Pierre-Marie; Righini, Marc; Perrier, Arnaud; Bertoletti, Laurent; Parent, Florence; Lorut, Christine; Meyer, Guy

    2013-09-01

    We analysed a cohort of patients with normotensive pulmonary embolism (PE) in order to assess whether combining echocardiography and biomarkers with the pulmonary embolism severity index (PESI) improves the risk stratification in comparison to the PESI alone. The PESI was calculated in normotensive patients with PE who also underwent echocardiography and assays of cardiac troponin I and brain natriuretic peptide. 30-day adverse outcome was defined as death, recurrent PE or shock. 529 patients were included, 25 (4.7%, 95% CI 3.2-6.9%) had at least one outcome event. The proportion of patients with adverse events increased from 2.1% in PESI class I-II to 8.4% in PESI class III-IV, and to 14.3% in PESI class V (p<0.001). In PESI class I-II, the rate of outcome events was significantly higher in patients with abnormal values of biomarkers or right ventricular dilatation. In multivariate analysis, the PESI (class III-IV versus I-II, OR 3.1, 95% CI 1.2-8.3; class V versus I-II, OR 5.5, 95% CI 1.5-25.5 and echocardiography (right ventricular/left ventricular ratio, OR (for an increase of 0.1) 1.3, 95% CI 1.1-1.5) were independent predictors of an adverse outcome. In patients with normotensive PE, biomarkers and echocardiography provided additional prognostic information to the PESI. PMID:23258789

  7. Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma

    PubMed Central

    Mima, Kosuke; Sukawa, Yasutaka; Li, Tingting; Yasunari, Mika; Zhang, Xuehong; Wu, Kana; Meyerhardt, Jeffrey A.; Fuchs, Charles S.

    2014-01-01

    Background Colorectal carcinoma (CRC) represents a group of histopathologically and molecularly heterogeneous diseases, which may contain signet-ring cell component and/or mucinous component to a varying extent under pathology assessment. However, little is known about the prognostic significance of those components, independent of various tumor molecular features. Methods Utilizing a molecular pathological epidemiology database of 1,336 rectal and colon cancers in the Nurses’ Health Study and the Health Professionals Follow-up Study, we examined patient survival according to the proportion of signet-ring cell and mucinous components in CRCs. Cox proportional hazards models were used to compute hazard ratio (HR) for mortality, adjusting for potential confounders including stage, microsatellite instability, CpG island methylator phenotype, LINE-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Results Compared to CRC without signet-ring cell component, 1–50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 1.40 [95 % confidence interval (CI) 1.02–1.93], and >50 % signet-ring cell component was associated with multivariate CRC-specific mortality HR of 4.53 (95 % CI 2.53–8.12) (Ptrend > 0.0001). Compared to CRC without mucinous component, neither 1–50 % mucinous component (multivariate HR 1.04; 95 % CI 0.81–1.33) nor >50 % mucinous component (multivariate HR 0.82; 95 % CI 0.54–1.23) was significantly associated with CRC-specific mortality (Ptrend < 0.57). Conclusions Even a minor (50 % or less) signet-ring cell component in CRC was associated with higher patient mortality, independent of various tumor molecular and other clinicopathological features. In contrast, mucinous component was not associated with mortality in CRC patients. PMID:25326395

  8. Pretreatment serum lactate dehydrogenase is an independent prognostic factor for patients receiving neoadjuvant chemotherapy for locally advanced cervical cancer.

    PubMed

    Li, Jing; Wu, Miao-Fang; Lu, Huai-Wu; Chen, Qing; Lin, Zhong-Qiu; Wang, Li-Juan

    2016-08-01

    For locally advanced cervical cancer (LACC), hypoxia is a characteristic property. This study aimed to investigate whether baseline lactic dehydrogenase (LDH) level, which is a marker of hypoxia, had clinical value in determining neoadjuvant chemotherapy (NACT) response and prognosis for LACC patients. The study cohort included 418 patients with a median follow-up of 37.5 months. Cox proportional hazards models were used to assess the prognostic value of baseline LDH levels. Multivariate logistic regression analysis was performed to identify independent predictors of complete response after NACT. Backward stepwise selection with the Akaike information criterion was used to identify factors that could be entered into the multivariate regression model. Compared with patients with LDH levels <252.0 μ/L, patients with LDH levels ≥252.0 μ/L were more likely to have an elevated level of squamous cell carcinoma antigen, lymphatic vascular space involvement, lymph node metastasis, and positive parametrium and achieved lower complete remission rates. Baseline LDH levels ≥252.0 μ/L was an independent prognosticator for recurrence-free survival (adjusted hazard ratio [HR], 3.56; 95% confidence interval [CI] 2.22-5.69; P < 0.0001) and cancer-specific survival (adjusted HR, 3.08; 95% CI, 1.89-5.01; P < 0.0001). The predictive value of baseline LDH value remained significant in the subgroup analysis. LDH level ≥252.0 μ/L was identified as an independent predictor of complete remission after NACT (adjusted odds ratio [OR], 0.29; 95% CI, 0.15-0.58; P < 0.0001). Baseline LDH ≥252.0 μ/L is an independent prognostic predictor for patients receiving neoadjuvant chemotherapy for LACC. It helps distinguish patients with different prognosis and select patients who are more likely to benefit from NACT. PMID:27350066

  9. Stromal Palladin Expression Is an Independent Prognostic Factor in Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Sato, Daisuke; Tsuchikawa, Takahiro; Mitsuhashi, Tomoko; Hatanaka, Yutaka; Marukawa, Katsuji; Morooka, Asami; Nakamura, Toru; Shichinohe, Toshiaki; Matsuno, Yoshihiro; Hirano, Satoshi

    2016-01-01

    It has been clear that cancer-associated fibroblasts (CAFs) in the tumor microenvironment play an important role in pancreatic ductal adenocarcinoma (PDAC) progression. However, how CAFs relate to the patients’ prognosis and the effects of chemoradiation therapy (CRT) has not been fully investigated. Tissue microarrays (TMAs) representing 167 resected PDACs without preoperative treatment were used for immunohistochemical studies (IHC) of palladin, α-smooth muscle actin (SMA), and podoplanin. Correlations between the expression levels of these markers and clinicopathological findings were analyzed statistically. Whole sections of surgical specimens from PDACs with and without preoperative CRT, designated as the chemotherapy-first group (CF, n = 19) and the surgery-first group (SF, n = 21), respectively, were also analyzed by IHC. In TMAs, the disease-specific survival rate (DSS) at 5 years for all 167 cases was 23.1%. Seventy cases (41.9%) were positive for palladin and had significantly lower DSS (p = 0.0430). α-SMA and podoplanin were positive in 167 cases (100%) and 131 cases (78.4%), respectively, and they were not significantly associated with DSS. On multivariable analysis, palladin expression was an independent poor prognostic factor (p = 0.0243, risk ratio 1.60). In the whole section study, palladin positivity was significantly lower (p = 0.0037) in the CF group (5/19) with a significantly better DSS (p = 0.0144) than in the SF group (16/22), suggesting that stromal palladin expression is a surrogate indicator of the treatment effect after chemoradiation therapy. PMID:27023252

  10. The prognostic significance of surface dipeptidylpeptidase IV (CD26) expression in B-cell chronic lymphocytic leukemia.

    PubMed

    Matuszak, Magdalena; Lewandowski, Krzysztof; Czyż, Anna; Kiernicka-Parulska, Jolanta; Przybyłowicz-Chalecka, Anna; Jarmuż-Szymczak, Małgorzata; Lewandowska, Maria; Komarnicki, Mieczysław

    2016-08-01

    A number of factors related to B-cell chronic lymphocytic leukemia (B-CLL) patients' prognosis have been identified. However, still some factors better reflecting disease activity in individual cases are explored. The study aimed to evaluate prognostic significance of dipeptidylpeptidase IV/CD26 expression on B-CLL cells and its relationship with other well established prognostic factors. The study included 94 patients with newly diagnosed B-CLL and involved analysis of clinical, laboratory, flow-cytometry and cytogenetic data. Detailed analysis showed that CD26 expression on B-CLL cells correlates with Rai's clinical stage of the disease at diagnosis (p=0.034), β2-microglobulin concentration (p=0.012), lactic acid dehydrogenase activity (p=0.045) and absolute lymphocytes' count (p=0.027) in the blood. The multivariate analysis revealed that time to treatment (TTT) was significantly influenced by Rai clinical stage, LDH activity in blood and CD26 expression on B-CLL cell's. Moreover, in the multivariate analysis restricted to the group of patients with documented cytogenetic risk (n=36) CD26 expression, Rai clinical stage and cytogenetic profile remained their independent impact on TTT. The results of our study indicate that the CD26 expression should be incorporated in B-CLL patients risk assessment along with well known prognostic factors, since it seems to have a relationship with the tumor mass and influences TTT. PMID:27376546

  11. Preoperative Plasma Fibrinogen Level Represents an Independent Prognostic Factor in a Chinese Cohort of Patients with Upper Tract Urothelial Carcinoma

    PubMed Central

    Jin, Jie; Zhou, Li-Qun; He, Zhi-Song; Shen, Cheng; He, Qun; Li, Jun; Liu, Li-Bo; Wang, Cong; Chen, Xiao-Yu; Fan, Yu; Hu, Shuai; Zhang, Lei; Yu, Wei; Han, Wen-Ke

    2016-01-01

    Background Increased plasma fibrinogen is thought to contribute to tumor progression and metastasis. The association of plasma fibrinogen with clinicopathological characteristics, and the optimal cutoff with an ideal predictive value has not been fully determined in patients with upper tract urothelial carcinoma (UTUC). We aimed to investigate the clinical significance of this parameter in a Chinese cohort of patients with UTUC. Methods A retrospective study was conducted to analyze the clinical data of 184 operable UTUC patients in a Chinese cohort with a high incidence of chronic kidney disease (CKD). An optimal cutoff was set for further analysis according to validated web-based software. The associations of plasma fibrinogen with clinicopathological characteristics and survival were assessed. Multivariate analyses were performed to determine the independent prognostic factors. Results Elevated plasma fibrinogen was significantly associated with tumor necrosis, lymph node involvement, and a higher preoperative CKD stage, pathological tumor stage and grade (all P < 0.05). Kaplan-Meier analysis showed that plasma fibrinogen ≥ 3.54 g/L predicted a poorer overall and cancer-specific survival than < 3.54 g/L (P < 0.001 for both). Multivariate analyses revealed that elevated preoperative plasma fibrinogen was an independent negative prognostic factor for overall survival (HR = 2.026; 95% CI: 1.226–3.349; P = 0.006) and cancer-specific survival (HR = 1.886; 95% CI: 1.019–3.490; P = 0.043). Conclusions Increased plasma fibrinogen was an independent prognostic risk factor for poor outcomes in UTUC. This parameter may serve as an effective biomarker with easy accessibility for evaluating prognosis for patients with UTUC. PMID:26930207

  12. Prognostic significance of X-ray cross-complementing gene 1 expression in gastric cancer

    PubMed Central

    Wang, Jian; Wang, Tongshan; Xu, Jun; Chen, WenJiao; Shi, Wei; Cheng, Jianfeng

    2016-01-01

    Objective The aim of this study is to identify the prognostic significance of X-ray cross-complementing gene 1 (XRCC1) in patients with gastric cancer undergoing surgery and platinum-based adjuvant chemotherapy. Methods Immunohistochemistry (IHC) was used to evaluate XRCC1 protein expression profiles on surgical specimens of 612 gastric cancer patients. The relationship between XRCC1 expression and existing prognostic factors, platinum-based adjuvant chemotherapy, disease-free survival (DFS) and overall survival (OS) were analyzed. Results Among 612 patients staged Ⅱ/Ⅲ in our study, 182 (29.74%) were evaluated as XRCC1 IHC positive. XRCC1 expression was not significantly related to OS (P = 0.347) or DFS (P = 0.297). Compared with surgery only, platinum-based adjuvant chemotherapy significantly improved the OS (P = 0.031). And the patients with negative XRCC1 expression benefited more from platinum-based adjuvant chemotherapy (P = 0.049). Multivariate analysis demonstrated that tumor size, T category, N category, vascular or nerve invasion and platinum-based chemotherapy were good prognostic factors for OS (P < 0.05). Though XRCC1 plays an important role in DNA repair pathways, no significant relationship is found in XRCC1 expression and OS among gastric cancer in our study. Conclusions XRCC1 might be an alternative prognostic marker for the patients of gastric cancer after radical resection. The patients with negative XRCC1 expression can benefit more from platinum-based adjuvant chemotherapy.

  13. Bioinformatics analyses of significant prognostic risk markers for thyroid papillary carcinoma.

    PubMed

    Min, Xiao-Shan; Huang, Peng; Liu, Xu; Dong, Chao; Jiang, Xiao-Lin; Yuan, Zheng-Tai; Mao, Lin-Feng; Chang, Shi

    2015-09-01

    This study was aimed to identify the prognostic risk markers for thyroid papillary carcinoma (TPC) by bioinformatics. The clinical data of TPC and their microRNAs (miRNAs) and genes expression profile data were downloaded from The Cancer Genome Atlas. Elastic net-Cox's proportional regression hazards model (EN-COX) was used to identify the prognostic associated factors. The receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) curve were used to screen the significant prognostic risk miRNA and genes. Then, the target genes of the obtained miRNAs were predicted followed by function prediction. Finally, the significant risk genes were performed literature mining and function analysis. Total 1046 miRNAs and 20531 genes in 484 cases samples were identified after data preprocessing. From the EN-COX model, 30 prognostic risk factors were obtained. Based on the 30 risk factors, 3 miRNAs and 11 genes were identified from the ROC and KM curves. The target genes of miRNA-342 such as B-cell CLL/lymphoma 2 (BCL2) were mainly enriched in the biological process related to cellular metabolic process and Disease Ontology terms of lymphoma. The target genes of miRNA-93 were mainly enriched in the pathway of G1 phase. Among the 11 prognostic risk genes, v-maf avian musculoaponeurotic fibrosarcoma oncogene homologue F (MAFF), SRY (sex-determining region Y)-box 4 (SOX4), and retinoic acid receptor, alpha (RARA) encoded transcription factors. Besides, RARA was enriched in four pathways. These prognostic markers such as miRNA-93, miRNA-342, RARA, MAFF, SOX4, and BCL2 may be used as targets for TPC chemoprevention. PMID:25908172

  14. Prognostic Significance of Premature Atrial Complexes Burden in Prediction of Long-Term Outcome

    PubMed Central

    Lin, Chin-Yu; Lin, Yenn-Jiang; Chen, Yun-Yu; Chang, Shih-Lin; Lo, Li-Wei; Chao, Tze-Fan; Chung, Fa-Po; Hu, Yu-Feng; Chong, Eric; Cheng, Hao-Min; Tuan, Ta-Chuan; Liao, Jo-Nan; Chiou, Chuen-Wang; Huang, Jin-Long; Chen, Shih-Ann

    2015-01-01

    Background The prognostic significance of premature atrial complex (PAC) burden is not fully elucidated. We aimed to investigate the relationship between the burden of PACs and long-term outcome. Methods and Results We investigated the clinical characteristics of 5371 consecutive patients without atrial fibrillation (AF) or a permanent pacemaker (PPM) at baseline who underwent 24-hour electrocardiography monitoring between January 1, 2002, and December 31, 2004. Clinical event data were retrieved from the Bureau of National Health Insurance of Taiwan. During a mean follow-up duration of 10±1 years, there were 1209 deaths, 1166 cardiovascular-related hospitalizations, 3104 hospitalizations for any reason, 418 cases of new-onset AF, and 132 PPM implantations. The optimal cut-off of PAC burden for predicting mortality was 76 beats per day, with a sensitivity of 63.1% and a specificity of 63.5%. In multivariate analysis, a PAC burden >76 beats per day was an independent predictor of mortality (hazard ratio: 1.384, 95% CI: 1.230 to 1.558), cardiovascular hospitalization (hazard ratio: 1.284, 95% CI: 1.137 to 1.451), new-onset AF (hazard ratio: 1.757, 95% CI: 1.427 to 2.163), and PPM implantation (hazard ratio: 2.821, 95% CI: 1.898 to 4.192). Patients with frequent PAC had increased risk of mortality attributable to myocardial infarction, heart failure, and sudden cardiac death. Frequent PACs increased risk of PPM implantation owing to sick sinus syndrome, high-degree atrioventricular block, and/or AF. Conclusions The burden of PACs is independently associated with mortality, cardiovascular hospitalization, new-onset AF, and PPM implantation in the long term. PMID:26316525

  15. Serum Matrix Metalloproteinase-7 is an independent prognostic biomarker in advanced bladder cancer

    PubMed Central

    2014-01-01

    Background Urine markers have been studied extensively but there is a lack of blood prognostic markers in bladder cancer. MMP-7 is produced by stromal cells and by tumor cells and is overexpressed in a variety of epithelial and mesenchymal tumors. In this study, we assessed with an immunoassay we developed, the prognostic value of serum MMP-7 in a series of patients with advanced bladder cancer. Methods Serum samples were collected from 56 patients with advanced bladder cancer who were treated at the Montpellier Cancer Institute between March 2003 and December 2004. MMP-7 was quantified in serum samples by using a homogeneous sandwich fluoroimmunoassay we developed based on the time resolved amplified cryptate emission (TRACE) technology. Results The median overall survival of the study population was 2.2 years (95% CI, 1.4 to 3.0) with 1- and 5-year survival rates of 73% (95% CI, 59% to 82%) and 25% (95% CI, 14% to 37%), respectively. High MMP-7 serum levels were associated with poor survival. Using a cut-off value of 11.5 ng/mL, the median overall survival was 3.0 years (95% CI, 1.5 to 5.1) for patients with MMP-7 serum level <11.5 ng/mL and 1.3 years (95% CI, 0.8 to 2.5) for patients with serum level ?11.5 ng/mL. Multivariate analysis identified high MMP-7 serum concentration as an independent prognostic factor for survival in patients with advanced bladder cancer (R?=?2.1, 95% CI, 1.1 to 4.4). Conclusions Our results show that the MMP-7 serum concentration is an independent prognostic factor in patients with locally advanced and or metastatic bladder cancer. PMID:25984271

  16. Prognostic significance of tissue miR-345 downregulation in non-small cell lung cancer

    PubMed Central

    Chen, Liming; Li, Xiaojie; Chen, Xiaojun

    2015-01-01

    Background: MiRNAs might function as oncogenes or tumor suppressor genes in the tumorigenesis process. Dysregulation of miR-345 is a frequent event in many types of human cancers. However, the tissue miR-345 expression level in non-small cell lung cancer (NSCLC) and its potential clinical significance remains unknown. Materials and methods: Real-time PCR was conducted to evaluate the expression level of miR-345 in NSCLC tissues as well as cell lines. Then the association between tissue miR-345 expression level and clinical outcome was investigated. Results: The expression level of miR-345 was significantly decreased in NSCLC tissues and cell lines compared with the controls (P<0.05; P<0.01). Tissue miR-345 expression level was associated with various clinicopathological parameters including LN metastasis (P=0.012), distant metastasis (P=0.007), TNM stage (P=0.008) and grade (P=0.030). In addition, the NSCLC patients in thelow tissue miR-345 expression group had significantly shorter 5-year overall survival time than those in the high tissue miR-345expression group (P=0.016). Multivariate analysis showed that tissue miR-345 was an independent risk factor for NSCLC (HR=3.921, 95% CI: 2.285-10.540; P=0.008). Conclusions: The expression level of miR-345 was reduced in NSCLC tissues and cell lines. Low tissue miR-345 expression was associated with progression and poor prognosis of NSCLC, indicating that tissue miR-345 may serve as a novel prognostic marker in NSCLC. PMID:26885027

  17. Severe muscle depletion in patients on the liver transplant wait list: its prevalence and independent prognostic value.

    PubMed

    Tandon, Puneeta; Ney, Michael; Irwin, Ivana; Ma, Mang M; Gramlich, Leah; Bain, Vincent G; Esfandiari, Nina; Baracos, Vickie; Montano-Loza, Aldo J; Myers, Robert P

    2012-10-01

    As detected by cross-sectional imaging, severe muscle depletion, which is termed sarcopenia, holds promise for prognostication in patients with cirrhosis. Our aims were to describe the prevalence and predictors of sarcopenia in patients with cirrhosis listed for liver transplantation (LT) and to determine its independent prognostic significance for the prediction of waiting-list mortality. Adults listed for LT who underwent abdominal computed tomography/magnetic resonance imaging within 6 weeks of activation were retrospectively identified. The exclusions were hepatocellular carcinoma, acute liver failure, prior LT, and listing for multivisceral transplantation or living related LT. Sixty percent of the 142 eligible patients were male, the median age was 53 years, and the median Model for End-Stage Liver Disease (MELD) score at listing was 15. Forty-one percent were sarcopenic; sarcopenia was more prevalent in males versus females (54% versus 21%, P < 0.001) and increased with the Child-Pugh class (10% for class A, 34% for class B, and 54% for class C, P = 0.007). Male sex, the dry-weight body mass index (BMI), and Child-Pugh class C cirrhosis (but not the MELD score) were independent predictors of sarcopenia. Sarcopenia was an independent predictor of mortality (hazard ratio = 2.36, 95% confidence interval = 1.23-4.53) after adjustments for age and MELD scores. In conclusion, sarcopenia is associated with increased waiting-list mortality and is poorly predicted by subjective nutritional assessment tools such as BMI and subjective global assessment. If this is validated in larger studies, the objective assessment of sarcopenia holds promise for prognostication in this patient population. PMID:22740290

  18. Prognostic significance of hyponatremia among ambulatory patients with heart failure and preserved and reduced ejection fractions.

    PubMed

    Bavishi, Chirag; Ather, Sameer; Bambhroliya, Arvind; Jneid, Hani; Virani, Salim S; Bozkurt, Biykem; Deswal, Anita

    2014-06-01

    Hyponatremia in heart failure (HF) is an established predictor of adverse outcomes in hospitalized patients with reduced ejection fraction (EF). However, there is a paucity of data in ambulatory patients with HF with preserved ejection fraction (HFpEF). We examined the prevalence, risk factors, and long-term outcomes of hyponatremia (serum sodium ≤135 mEq/L) in ambulatory HFpEF and HF with reduced EF (HFrEF) in a national cohort of 8,862 veterans treated in Veterans Affairs clinics. Multivariable logistic regression models were used to identify factors associated with hyponatremia, and multivariable Cox proportional hazard models were used for analysis of outcomes. The cohort consisted of 6,185 patients with HFrEF and 2,704 patients with HFpEF with a 2-year follow-up. Hyponatremia was present in 13.8% and 12.9% patients in HFrEF and HFpEF, respectively. Hyponatremia was independently associated with younger age, diabetes, lower systolic blood pressure, anemia, body mass index <30 kg/m(2), and spironolactone use, whereas African-American race and statins were inversely associated. In multivariate analysis, hyponatremia remained a significant predictor of all-cause mortality in both HFrEF (hazards ratio [HR] 1.26, 95% confidence interval [CI] 1.11 to 1.44, p <0.001) and HFpEF (HR 1.40, 95% CI 1.12 to 1.75, p = 0.004) and a significant predictor of all-cause hospitalization in patients with HFrEF (HR 1.18, 95% CI 1.07 to 1.31, p = 0.001) but not in HFpEF (HR 1.08, 95% CI 0.92 to 1.27, p = 0.33). In conclusion, hyponatremia is prevalent at a similar frequency of over 10% in ambulatory patients with HFpEF and HFrEF. Hyponatremia is an independent prognostic marker of mortality across the spectrum of patients with HFpEF and HFrEF. In contrast, it is an independent predictor for hospitalization in patients with HFrEF but not in patients with HFpEF. PMID:24837261

  19. Prognostic Significance of Survivin Expression in Osteosarcoma Patients: A Meta-Analysis

    PubMed Central

    Liu, Yugang; Teng, Zhaowei; Wang, Ying; Gao, Pengfei; Chen, Junli

    2015-01-01

    Background Osteosarcoma is the most common primary bone malignancy and has poor prognosis. Survivin has been identified as an independent prognostic factor for a majority of cancers. In the present study, we evaluated the effect of survivin expression on the clinical outcome of osteosarcoma patients. Material/Methods Online electronic databases were searched for related articles published between 2000 and 2015. Odds ratio (OR) and risk ratio (RR) with their 95% confidence intervals (CI) were employed to calculate the significance. Results Overall, a total of 20 relevant studies were selected, including 1030 patients. No significant heterogeneity was observed among included studies (P>0.01, I2<50%). Survivin was expressed in 68.6% of all cases. Our results show that survivin expression increased the 5-year overall survival (RR=0.48, 95% CI=0.32–0.71, P=0.0002) and rate of postoperative recurrence (RR=1.80, 95% CI=1.09–2.97, P=0.02). It was associated with the grade of osteosarcoma (Enneking clinical stage, IIb–III vs. I–IIa: OR=5.26, 95% CI=3.76–7.34, P<0.00001; Price’s grade, III vs. I+II: OR=2.04, 95% CI=1.16–3.61, P=0.01), metastasis, and soft tissue invasion of osteosarcoma (OR=6.25, 95% CI=3.74–10.45, P<0.00001; OR=6.15, 95% CI=3.74–10.11, P<0.00001). No relationship was found between survivin expression and sex, age, or tumor size in patients with osteosarcoma. Conclusions Our results suggest that survivin can function as a new diagnostic biomarker for osteosarcoma and be used as a reference index to determine pathology classification of osteosarcoma, providing new targets for gene therapy of osteosarcoma. PMID:26408642

  20. Validation and Recalibration of Two Multivariable Prognostic Models for Survival and Independence in Acute Stroke

    PubMed Central

    Teece, Lucy; Dennis, Martin S.; Roffe, Christine

    2016-01-01

    Introduction Various prognostic models have been developed for acute stroke, including one based on age and five binary variables (‘six simple variables’ model; SSVMod) and one based on age plus scores on the National Institutes of Health Stroke Scale (NIHSSMod). The aims of this study were to externally validate and recalibrate these models, and to compare their predictive ability in relation to both survival and independence. Methods Data from a large clinical trial of oxygen therapy (n = 8003) were used to determine the discrimination and calibration of the models, using C-statistics, calibration plots, and Hosmer-Lemeshow statistics. Methods of recalibration in the large and logistic recalibration were used to update the models. Results For discrimination, both models functioned better for survival (C-statistics between .802 and .837) than for independence (C-statistics between .725 and .735). Both models showed slight shortcomings with regard to calibration, over-predicting survival and under-predicting independence; the NIHSSMod performed slightly better than the SSVMod. For the most part, there were only minor differences between ischaemic and haemorrhagic strokes. Logistic recalibration successfully updated the models for a clinical trial population. Conclusions Both prognostic models performed well overall in a clinical trial population. The choice between them is probably better based on clinical and practical considerations than on statistical considerations. PMID:27227988

  1. Moderate level of HER2 expression and its prognostic significance in breast cancer with intermediate grade.

    PubMed

    Ignatov, Tanja; Eggemann, Holm; Burger, Elke; Fettke, Franziska; Costa, Serban Dan; Ignatov, Atanas

    2015-06-01

    Overexpression of human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive marker of response to anti-HER2 therapy in breast cancer. Our goal was to analyze the prognostic significance of moderate expression of HER2 in breast cancer with intermediate differentiation grade. We performed a multicenter retrospective register study of 8494 patients with primary non-metastatic breast cancer admitted between 2000 and 2011 to eight Clinics in Saxony-Anhalt, federal state of Germany. Patients were divided into three groups according to their HER2 score: 4073 were classified as HER2 negative (HER2 0 and 1+), 822 HER2 moderate (HER2 2+/HER2), and 1238 HER2 positive (HER2 3+ or HER2 2+/HER2+). HER2-positive cases were excluded from analysis. Tumors with moderate HER2 (HER2 2+) expression demonstrated an aggressive behavior and worse patient survival compared with HER2 0 and 1+ status. HER2 2+ status was associated with shorter median overall survival (OS) (P < 0.0001) in breast cancer patients with an intermediate grade of differentiation. Comparing low-grade and high-grade tumors, HER2 moderate expression did not significantly influence patient survival. In multivariate analysis after adjustment for other prognostic factors HER2 2+ status remained an unfavorable prognostic factor for OS (HR 1.224, 95 % CI 1.059-1.415, P = 0.006) in breast cancer patients with an intermediate grade of differentiation. HER2 2+ status is an unfavorable prognostic factor regarding the OS of breast cancer patients with intermediate grade of differentiation and could be used to identify patients, who may benefit from adjuvant therapy. PMID:25926338

  2. Prognostic significance of RNA-dependent protein kinase (PKR) on non-small cell lung cancer patients

    PubMed Central

    Pataer, Abujiang; Raso, Maria Gabriela; Correa, Arlene M; Behrens, Carmen; Tsuta, Koji; Solis, Luisa; Fang, Bingliang; Roth, Jack A.; Wistuba, Ignacio I.; Swisher, Stephen G.

    2011-01-01

    Purpose The role of RNA-dependent protein kinase (PKR) in antiviral defence mechanisms and in cellular differentiation, growth, and apoptosis is well known, but the role of PKR in human lung cancer remains poorly understood. To explore the role of PKR in human lung cancer, we evaluated PKR’s expression in tissue microarray specimens from both non-small cell lung cancer (NSCLC) and normal human bronchial epithelium tissue. Experimental Design Tissue microarray samples (TMA-1) from 231 lung cancers were stained with PKR antibody and validated on TMA-2 from 224 lung cancers. Immunohistochemical expression score was quantified by three pathologists independently. Survival probability was computed by the Kaplan-Meier method. Results The NSCLC cells showed lower levels of PKR expression than normal bronchial epithelium cells did. We also found a significant association between lower levels of PKR expression and lymph node metastasis. We found that loss of PKR expression is correlated with a more aggressive behavior, and that a high PKR expression predicts a subgroup of patients with a favorable outcome. Univariate and multivariate Cox proportional hazards regression models showed that a lower level of PKR expression was significantly associated with shorter survival in NSCLC patients. We further validated and confirmed that PKR to be a powerful prognostic factor in TMA-2 lung cancer (HR=0.22, P<0.0001). Conclusions Our findings first indicate that PKR expression is an independent prognostic variable in NSCLC patients. PMID:20930042

  3. Long-term prognostic significance of M mode echocardiography in young men after myocardial infarction.

    PubMed Central

    Eriksson, S. V.; Caidahl, K.; Hamsten, A.; de Faire, U.; Rehnqvist, N.; Lindvall, K.

    1995-01-01

    OBJECTIVE--To evaluate the power of measurements of left ventricular size and function for predicting long term (82 month) mortality by performing echocardiography in 97 men who had survived an acute myocardial infarction. SETTING--University hospital specialising in cardiology. PARTICIPANTS--97 consecutive male patients who had survived a myocardial infarction. MAIN OUTCOME MEASURES--The additive prognostic value of functional measurements to that provided by primary risk factors (smoking habits and lipoprotein levels), radiological heart size, exercise capacity, and number of major coronary arteries with haemodynamically significant stenoses was evaluated. An echo index was calculated from three echocardiographic variables (yielding one score point each if: left ventricular diameter at the end of diastole (LVDD) > or = 5.7 cm, left ventricular fractional shortening < or = 24%, and E point-separation (EPSS) > or = 10 mm). MAIN OUTCOME--17 cardiac deaths occurred during follow up. RESULTS--Univariate analysis showed that treatment with loop diuretics for heart failure (P < 0.01), LVDD (P < 0.01), left ventricular diameter at the end of systole (LVDS) (P < 0.001), left atrial diameter (P < 0.001), fractional shortening (P < 0.05), and echo index (P < 0.001) were all associated with cardiac death. Angiographically determined regional wall motion disturbances (P < 0.005) and angiographic ejection fraction (P < 0.001) were also associated with cardiac death, as was the number of major coronary arteries with significant stenosis (P < 0.05). When all significant echocardiographic variables from univariate analysis were entered into Cox proportional hazards survival analysis, LVDS and left atrial diameter contributed independently to the prediction of cardiac death. If angiographic data were also entered into the model, the echo index made an independent contribution to the prediction of cardiac death. CONCLUSIONS--Among young male patients with a previous myocardial

  4. Bayesian Test of Significance for Conditional Independence: The Multinomial Model

    NASA Astrophysics Data System (ADS)

    de Morais Andrade, Pablo; Stern, Julio; de Bragança Pereira, Carlos

    2014-03-01

    Conditional independence tests (CI tests) have received special attention lately in Machine Learning and Computational Intelligence related literature as an important indicator of the relationship among the variables used by their models. In the field of Probabilistic Graphical Models (PGM)--which includes Bayesian Networks (BN) models--CI tests are especially important for the task of learning the PGM structure from data. In this paper, we propose the Full Bayesian Significance Test (FBST) for tests of conditional independence for discrete datasets. FBST is a powerful Bayesian test for precise hypothesis, as an alternative to frequentist's significance tests (characterized by the calculation of the \\emph{p-value}).

  5. Serum HE4: An Independent Prognostic Factor in Non-Small Cell Lung Cancer

    PubMed Central

    Lamy, Pierre-Jean; Plassot, Carine; Pujol, Jean-Louis

    2015-01-01

    Human epididymis secretory protein 4 (HE4) is a secreted glycosylated protein encoded by the WAP four-disulfide core domain 2 (WFDC2) gene, located on a chromosome 20 segment that is frequently amplified in many cancers. This study aimed at determining serum HE4 prognostic value in non-small cell lung cancer (NSCLC), following the REMARK guidelines. Serum samples from 346 consecutive patients with histologically proven and previously untreated NSCLC and 41 patients with benign pulmonary disease were collected at the Montpellier-Nimes Academic Hospital. Work-up investigations performed to determine the disease characteristics and treatment algorithms were congruent with international guidelines. HE4 levels in serum were measured with an ELISA test (Fujirebio Diagnostics) that uses two monoclonal antibodies, 2H5 and 3D8, against the C-WFDC domain of HE4. The area under the ROC curve (i.e., overall ability of HE4 to discriminate between controls and patients) was 0.78 (95% confidence interval [CI], 0.738–0.821; z test P <0.0001). Serum HE4 levels were significantly higher in patients with worse performance status, advanced TNM stage and positive nodal status. In the Cox model, overall survival was shorter in patients with high pretreatment serum HE4 (above 140 pmol/L) than in patients with serum H4 level ≤ 140 pmol/L [median survival: 17.7 weeks (95% CI, 11.9 to 24.9) and 46.4 weeks (95% CI, 38.6 to 56.3), respectively; hazard ratio: 1.48 (95% CI, 1.12 to 1.95) for high HE4; adjusted P = 0.0057]. High serum HE4 level at diagnosis is an independent determinant of poor prognosis in NSCLC. PMID:26030627

  6. Prognostics

    NASA Technical Reports Server (NTRS)

    Goebel, Kai; Vachtsevanos, George; Orchard, Marcos E.

    2013-01-01

    Knowledge discovery, statistical learning, and more specifically an understanding of the system evolution in time when it undergoes undesirable fault conditions, are critical for an adequate implementation of successful prognostic systems. Prognosis may be understood as the generation of long-term predictions describing the evolution in time of a particular signal of interest or fault indicator, with the purpose of estimating the remaining useful life (RUL) of a failing component/subsystem. Predictions are made using a thorough understanding of the underlying processes and factor in the anticipated future usage.

  7. Genomic deletion of chromosome 12p is an independent prognostic marker in prostate cancer

    PubMed Central

    Kluth, Martina; Ahrary, Ramin; Hube-Magg, Claudia; Ahmed, Malik; Volta, Heinke; Schwemin, Catina; Steurer, Stefan; Wittmer, Corinna; Wilczak, Waldemar; Burandt, Eike; Krech, Till; Adam, Meike; Michl, Uwe; Heinzer, Hans; Salomon, Georg; Graefen, Markus; Koop, Christina; Minner, Sarah; Simon, Ronald; Sauter, Guido; Schlomm, Thorsten

    2015-01-01

    Deletion of 12p is a recurrent alteration in prostate cancer, but the prevalence and clinical consequences of this alteration have not been studied in detail. Dual labeling fluorescence in situ hybridization using probes for 12p13 (CDKN1B; p27) and centromere 12 as a reference was used to successfully analyze more than 3700 prostate cancers with clinical follow-up data assembled in a tissue microarray format. CDKN1B was selected as a probe because it is located in the center of the deletion, which spans > 10 Mb and includes > 50 genes in 80% of cancers with 12p deletion. Deletion of 12p was found in 13.7% of cancers and included 13.5% heterozygous and 0.2% homozygous deletions. 12p deletion were linked to advanced tumor stage (p < 0.0001), high Gleason grade (p < 0.0001), rapid tumor cell proliferation (p < 0.0001), lymph node metastasis (p = 0.0004), and biochemical recurrence (p = 0.0027). Multivariate analysis including pT stage (p < 0.0001), Gleason grade (p < 0.0001), pN status (p = 0.0001), preoperative PSA levels (p = 0.0001), and resection margin status (p = 0.0001) revealed an independent prognostic value of 12p deletion (p = 0.0014). Deletion of 12p was unrelated to the ERG fusion status. Deletion of 12p was only marginally linked to reduced p27 expression, which by itself was unrelated to clinical outcome. This argues against p27 as the key target gene of 12p deletions. In summary, the results of our study demonstrate that 12p deletion is frequent in prostate cancer and provides independent prognostic information. 12p deletion analysis alone, or in combination with other prognostic parameters may thus have clinical utility. PMID:26293672

  8. Prognostic significance of intraoperative macroscopic serosal invasion finding when it shows a discrepancy in pathologic result gastric cancer

    PubMed Central

    Kang, Sang Yull; Park, Ho Sung

    2016-01-01

    Purpose Depth of wall invasion is an important prognostic factor in patients with gastric cancer, whereas the prognostic significance of intraoperative macroscopic serosal invasion (mSE) findings remain unclear when they show a discrepancy in pathologic findings. This study, therefore, assessed the prognostic significance of mSE. Methods Data from cohort of 2,835 patients with resectable gastric cancer who underwent surgery between 1990 and 2010 were retrospectively reviewed. Results The overall accuracy of mSE and pathologic results was 83.4%. The accuracy of mSE was 75.5% in pT2. On the other hand, the accuracy of pT3 dropped to 24.5%. According to mSE findings (+/–), the 5-year disease-specific survival (DSS) rate differed significantly in patients with pT2 (+; 74.2% vs. –; 92.0%), pT3 (+; 76.7% vs. –; 91.8%) and pT4a (+; 51.3% vs. –; 72.8%) (P < 0.001 each), but not in patients with T1 tumor. Multivariate analysis showed that mSE findings (hazard ratio [HR], 2.275; 95% confidence interval [CI], 1.148–4.509), tumor depth (HR, 6.894; 95% CI, 2.325–20.437), nodal status (HR, 5.206; 95% CI, 2.298–11.791), distant metastasis (HR, 2.881; 95% CI, 1.388–6.209), radical resection (HR, 2.002; 95% CI, 1.017–3.940), and lymphatic invasion (HR, 2.713; 95% CI, 1.424–5.167) were independent predictors of 5-year DSS rate. Conclusion We observed considerable discrepancies between macroscopic and pathologic diagnosis of serosal invasion. However, macroscopic diagnosis of serosal invasion was independently prognostic of 5-year DSS. It suggests that because the pathologic results could not be perfect and the local inflammatory change with mSE(+) could affect survival, a combination of mSE(+/–) and pathologic depth may be predictive of prognosis in patients with gastric cancer. PMID:27186569

  9. ARID1A expression in early stage colorectal adenocarcinoma: an exploration of its prognostic significance.

    PubMed

    Lee, Lik Hang; Sadot, Eran; Ivelja, Sinisa; Vakiani, Efsevia; Hechtman, Jaclyn F; Sevinsky, Christopher J; Klimstra, David S; Ginty, Fiona; Shia, Jinru

    2016-07-01

    ARID1A is a chromatin remodeling gene that is mutated in a number of cancers including colorectal carcinoma (CRC). Loss of ARID1A has been associated with an adverse outcome in some types of cancer. However, literature data have not been consistent. Major limitations of some outcome studies include small sample size and heterogeneous patient population. In this study, we evaluated the prognostic value of ARID1A in a homogeneous group of early stage CRC patients, a population where prognostic markers are particularly relevant. We collected a retrospective series of 578 stage I or II CRCs. All patients underwent surgery with curative intent and without neoadjuvant or adjuvant therapy. ARID1A expression was analyzed by immunohistochemistry using tissue microarray. We found ARID1A loss in 49 of 552 analyzable tumors (8.9%). Compared with the ARID1A-retained group, cases with ARID1A loss were associated with female sex (P<.001), mismatch-repair protein deficiency (P<.001), poor differentiation (P<.001), lymphovascular invasion (P=.001), and higher pT stage (P=.047). However, at a median follow-up of 49months, ARID1A loss did not correlate with overall, disease-specific, or recurrence-free survival. This is the first systematic analysis to evaluate the prognostic significance of ARID1A in stage I/II CRCs, and our data indicate that ARID1A loss lacks prognostic significance in this population despite its association with other adverse features. Such data are clinically relevant, as efforts are ongoing in identifying markers that can detect the small but significant subset of early stage CRCs that will have a poor outcome. PMID:26980037

  10. Prognostic significance of oncogenic markers in ductal carcinoma in situ of the breast: a clinicopathologic study.

    PubMed

    Altintas, Sevilay; Lambein, Kathleen; Huizing, Manon T; Braems, Geert; Asjoe, Fernando Tjin; Hellemans, Hilde; Van Marck, Eric; Weyler, Joost; Praet, Marleen; Van den Broecke, Rudy; Vermorken, Jan B; Tjalma, Wiebren A

    2009-01-01

    Ductal carcinoma in situ (DCIS) is a heterogeneous malignant condition of the breast with an excellent prognosis. Until recently mastectomy was the standard treatment. As the results of the National Surgical Adjuvant Breast and Bowel Project-17 trial and the introduction of the Van Nuys Prognostic Index (VNPI) less radical therapies are used. Objectives are to identify clinicopathologic and biologic factors that may predict outcome. Cases of DCIS diagnosed in two Belgian University Centers were included. Paraffin-embedded material and Hematoxylin and Eosin stained slides of DCIS cases were reviewed and tumor size, margin width, nuclear grade, and comedo necrosis were assessed. Molecular markers (estrogen receptor, progesterone receptor, HER1-4, Ki67, and c-myc) were assayed immunohistochemically. Applied treatment strategies were correlated with the prospective use of the VNPI score. Kaplan-Meier survival plots were generated with log-rank significance and multiple regression analysis was carried out using Cox proportional hazards regression analysis; 159 patients were included with a median age of 54 years (range 29-78); 141 had DCIS and 18 DCIS with microinvasion. The median time of follow-up was 54 months (range 5-253). Twenty-three patients developed a recurrence (14.5%). The median time to recurrence was 46 months (range 5-253). Before the introduction of the VNPI, 37.5% of the DCIS patients showed a recurrence while thereafter 6.7% recurred (p < 0.005). Two recurrences occurred in the VNPI group I (7.1%); seven in the VNPI group II (8.5%) (median time to recurrence 66.3 months) and 14 in the VNPI group III (28.5%) (median time to recurrence 40.2 months) (disease-free survival [DFS]: p < 0.05). A Cox proportional hazards regression analysis indicated that tumor size, margin width, pathologic class, and age were independent predictors of recurrence, but none of the studied molecular markers showed this. Overexpression of HER4 in the presence of HER3 was found

  11. Prognostic significance of pretreatment albumin/globulin ratio in patients with hepatocellular carcinoma

    PubMed Central

    Deng, Yan; Pang, Qing; Miao, Run-Chen; Chen, Wei; Zhou, Yan-Yan; Bi, Jian-Bin; Liu, Su-Shun; Zhang, Jing-Yao; Qu, Kai; Liu, Chang

    2016-01-01

    Background Pretreatment nutritional and immunological statuses play an indispensable role in predicting the outcome of patients with various types of malignancies. The purpose of this study is to evaluate the predictive value of albumin/globulin ratio (AGR) in overall survival (OS) and recurrence in patients with hepatocellular carcinoma (HCC) following radical hepatic carcinectomy. Patients and methods This retrospective study included a total of 172 patients with HCC with complete medical and follow-up information between 2002 and 2012. AGR was calculated according to the following formula: AGR = albumin/globulin. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value. The associations of AGR with clinicopathological characteristics and prognosis were assessed. Further multivariate analysis using Cox regression model and subgroup analysis was performed to evaluate the predictive value. Results Receiver operating characteristic curve determined 37.65, 31.99, and 1.48 as the optimal cutoff values of albumin, globulin, and AGR in terms of 5-year OS or death, respectively. On the basis of the cutoff value of AGR, all the patients were divided, respectively, into low-AGR (n=105) and high-AGR (n=67) groups. AGR was found to be significantly correlated with age, cancer embolus, international normalized ratio, and postoperative outcome (P<0.05). Hepatitis B virus infection (hazard ratio [HR]: 2.125; 95% confidence interval [CI]: 1.285–3.153), tumor node metastasis stage (HR: 1.656; 95% CI: 1.234–2.223), serum albumin (HR: 0.546; 95% CI: 0.347–0.857), and AGR (HR: 0.402; 95% CI: 0.233–0.691) were independent predictors of OS via univariate and multivariate survival analyses. However, alpha-fetoprotein (HR: 1.708; 95% CI: 1.027–2.838), tumor node metastasis stage (HR: 1.464; 95% CI: 1.078–1.989), and AGR (HR: 0.493; 95% CI: 0.293–0.828) functioned as independent risk variables for predicting recurrence. Moreover

  12. Prognostic significance of phosphorylated 4E-binding protein 1 in non-small cell lung cancer

    PubMed Central

    Lee, Hyoun Wook; Lee, Eun Hee; Lee, Ji Hyun; Kim, Jeong-Eun; Kim, Seok-Hyun; Kim, Tae Gyu; Hwang, Sang Won; Kang, Kyung Woo

    2015-01-01

    Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) results in release of eIF4E, which sequentially relieves translational repression and enhances oncogenic protein synthesis. We assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in non-small cell lung cancer (NSCLC) and its correlation with clinicopathological parameters and patient survival. In addition, we investigated whether phosphorylation site made a difference in outcome. Tissue microarray blocks were generated from 73 NSCLC samples and immunohistochemically stained for p-4E-BP1 Thr37/46 and p-4E-BP1 Thr70. Both p-4E-BP1 Thr37/46 and p-4E-BP1 Thr70 were more highly expressed in squamous cell carcinoma than in adenocarcinoma (P = 0.006 and P = 0.003, respectively). Expression of p-4E-BP1 Thr70 was higher in tumours with a diameter larger than 3 cm (P = 0.024) and nodal metastasis (P = 0.053). High p-4E-BP1 Thr70 expression significantly correlated with worse overall survival (P = 0.001) and was an independent prognostic factor (hazard ratio 2.64, P = 0.004). p-4E-BP1 Thr37/46 had no prognostic significance. Phosphorylation site affected the prognostic significance of p-4E-BP1. p-4E-BP1 Thr70 is a candidate biomarker to predict poor prognosis in patients with NSCLC. PMID:26097581

  13. Predictive Significance of a New Prognostic Score for Patients With Diffuse Large B-Cell Lymphoma in the Interim-Positron Emission Tomography Findings

    PubMed Central

    Kong, Yu; Qu, Lili; Li, Yuekai; Liu, Dai; Lv, Xuemin; Han, Jiankui

    2016-01-01

    Abstract We hypothesized that the objective treatment response of patients with diffuse large B-cell lymphoma (DLBCL) was affected by many factors such as pathophysiological, biological, and pharmaceutical mechanisms. This retrospective study aimed to evaluate the predictive significance of clinical prognostic factors and interim fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), and to find a new prognostic predictor significantly associated with DLBCL patients’ outcome. A total of 105 adult patients with DLBCL were reviewed. Each patient underwent an interim 18F-FDG PET/CT scan after the second chemotherapy cycle. The visual method based on the Deauville 5-point scale was used to evaluate the interim-PET/CT scans. The relationships among the prognostic factors, the 3-year progression-free survival (PFS) rate and overall survival (OS) rate were analyzed with Kaplan–Meier plots. The predictive value of the newly constructed prognostic score was analyzed with multivariate analysis (Cox proportional hazard regression model). The visual analysis showed statistically significant differences in both PFS and OS between the patients with a negative interim-PET/CT and those with a positive interim-PET/CT. Advanced age, advanced stage, and DLBCL subtype were also significantly associated with outcome. A new prognostic score that composed of the above 4 factors was obtained. New prognostic score stratified patients into 4 risk groups with 3-year PFS of 98.5%, 73.9%, 11.1%, and 0%, and 3-year OS of 100%, 91.3%, 55.6%, and 0% (P < 0.001 for PFS and OS). Multivariate analysis showed that the new prognostic score had the greatest ability to predict relapse (P < 0.001) and death (P < 0.001). In DLBCL patients, interim 18F-FDG PET/CT can provide significant independent prognostic information. Our work illustrates that the new prognostic score has the strongest potential for accurately prognostication, for

  14. Progress on the cardiotoxicity of sunitinib: Prognostic significance, mechanism and protective therapies.

    PubMed

    Yang, Yi; Bu, Peili

    2016-09-25

    Tyrosine kinase inhibitors (TKIs) are multi-targeted anti-cancer agents effective in the treatment of renal cell carcinoma (RCC), imatinib-resistant gastrointestinal stromal tumor (GIST) and pancreatic cancer (PC). Targeting and inhibiting a wide range of oncogenically relevant receptor tyrosine kinases (RTKs), TKIs have been the golden standard treatment of several types of cancer. The cardiotoxicity of TKIs, however, has also emerged alongside their anti-cancer potencies and has attracted research attention. Over the past few years significant progress has been made in developing a deeper understanding of aspects such as extent of cardiotoxicity, prognostic implications and survival predictions, toxicological mechanisms, and potential cardioprotective therapies. In this review we focus on a typical TKI sunitinib and summarize the up-to-date knowledge of sunitinib-induced cardiac abnormalities reported in clinical studies, weighing their implications of prognostic values. We also examine recent findings in underlying mechanisms, and development of potential cardioprotective agents. PMID:27531228

  15. Oxygen-modifying treatment with ARCON reduces the prognostic significance of hemoglobin in squamous cell carcinoma of the head and neck

    SciTech Connect

    Hoogsteen, Ilse J. . E-mail: i.hoogsteen@rther.umcn.nl; Pop, Lucas A.M.; Marres, Henri A.M.; Hoogen, Franciscus J.A. van den; Kaanders, Johannes H.A.M.

    2006-01-01

    Purpose: To evaluate the prognostic significance of hemoglobin (Hb) levels measured before and during treatment with accelerated radiotherapy with carbogen and nicotinamide (ARCON). Methods and Materials: Two hundred fifteen patients with locally advanced tumors of the head and neck were included in a phase II trial of ARCON. This treatment regimen combines accelerated radiotherapy for reduction of repopulation with carbogen breathing and nicotinamide to reduce hypoxia. In these patients, Hb levels were measured before, during, and after radiotherapy. Results: Preirradiation and postirradiation Hb levels were available for 206 and 195 patients respectively. Hb levels below normal were most frequently seen among patients with T4 (p < 0.001) and N2 (p < 0.01) disease. Patients with a larynx tumor had significantly higher Hb levels (p < 0.01) than other tumor sites. During radiotherapy, 69 patients experienced a decrease in Hb level. In a multivariate analysis there was no prognostic impact of Hb level on locoregional control, disease-free survival, and overall survival. Primary tumor site was independently prognostic for locoregional control (p = 0.018), and gender was the only prognostic factor for disease-free and overall survival (p < 0.05). High locoregional control rates were obtained for tumors of the larynx (77%) and oropharynx (72%). Conclusion: Hemoglobin level was not found to be of prognostic significance for outcome in patients with squamous cell carcinoma of the head and neck after oxygen-modifying treatment with ARCON.

  16. CLIF–SOFA score and SIRS are independent prognostic factors in patients with hepatic encephalopathy due to alcoholic liver cirrhosis

    PubMed Central

    Jeong, Jin Hee; Park, In Sung; Kim, Dong Hoon; Kim, Seong Chun; Kang, Changwoo; Lee, Soo Hoon; Kim, Tae Yun; Lee, Sang Bong

    2016-01-01

    Abstract Hepatic encephalopathy (HE) is a complication associated with worst prognosis in decompensated liver cirrhosis (LC) patients. Previous studies have identified prognostic factors for HE, and recent studies reported an association between systemic inflammatory response syndrome (SIRS) and liver disease. This study aimed to identify prognostic factors for 30-day mortality in alcoholic LC patients with HE who visited the emergency department (ED). This was a retrospective study of alcoholic LC patients with HE from January 1, 2010, to April 30, 2015. The baseline characteristics, complications of portal hypertension, laboratory values, Child–Pugh class, Model for End-stage Liver Disease (MELD) score, chronic liver failure-sequential organ failure assessment (CLIF–SOFA) score, and SIRS criteria were assessed. The presence of 2 or more SIRS criteria was considered SIRS. The primary outcomes were 30-day mortality and prognostic factors for patients with HE visiting the ED. In total, 105 patients who met the inclusion criteria were analyzed. Overall, the 30-day mortality rate was 6.7% (7 patients). Significant variables were hepatorenal syndrome, international normalized ratio, white blood cell count, total bilirubin level, MELD score CLIF–SOFA score, and SIRS in univariate analysis. CLIF–SOFA score and SIRS were the significant factors in the multivariate analysis (hazard ratio 5.56, 15.98; 95% confidence interval 1.18–26.18, 1.58–161.37; P = 0.03, P = 0.02). The mortality rates differed according to the CLIF–SOFA score (P < 0.01). The CLIF–SOFA score and SIRS in alcoholic LC patients with HE visiting the ED are independent predictors of 30-day mortality. PMID:27367990

  17. Predictive and prognostic significance of circulating endothelial cells in advanced non-small cell lung cancer patients.

    PubMed

    Yuan, Dong-mei; Zhang, Qin; Lv, Yan-ling; Ma, Xing-qun; Zhang, Yan; Liu, Hong-bing; Song, Yong

    2015-11-01

    The aim of this study was to evaluate the predictive and prognostic values of circulating endothelial cells (CECs) in patients with advanced non-small cell lung cancer (NSCLC). A total of 102 newly diagnosed advanced NSCLC patients were enrolled in this study. The amount of CECs was enumerated by flow cytometry (CD45- CD31+ CD146+) at baseline. CEC counts of 56 patients were detected before and after two cycles of chemotherapy. We correlated the baseline and reduction of CECs after therapy with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The CEC level was significantly higher in advanced NSCLC patients, ranging from 57 to 1300 cells/10(5) cells (mean ± SD = 299 ± 221 cells/10(5) cells), than in patients with benign lesions (205 ± 97 cells/10(5) cells) and healthy volunteers (117 ± 33 cells/10(5) cells). When the cutoff value of CEC counts was 210 cells/10(5) cells, there was no significant association between CEC counts and OR/PFS/OS of the enrolled patients. However, patients with CEC response after chemotherapy have more chances to achieve OR (P < 0.001), and such patients showed longer PFS (P = 0.048) and OS (P = 0.018) than those without CEC response. In the multivariate analysis, the independent prognostic roles of brain metastasis (HR 6.165, P = 0.001), and CEC response (HR 0.442, P = 0.044) were found. The CEC counts could be considered as diagnostic biomarker for advanced NSCLC patients. And the reduction of CECs after treatment might be more ideal than the baseline CEC counts as a predictive or prognostic factor in patients treated with chemotherapy or anti-angiogenic therapy. PMID:26084612

  18. The prognostic significance of Smad3, Smad4, Smad3 phosphoisoform expression in esophageal squamous cell carcinoma.

    PubMed

    Cho, Soo Youn; Ha, Sang Yun; Huang, Song-Mei; Kim, Jeong Hoon; Kang, Myung Soo; Yoo, Hae-Yong; Kim, Hyeon-ho; Park, Cheol-Keun; Um, Sung-Hee; Kim, Kyung-Hee; Kim, Seok-Hyung

    2014-11-01

    Smad3 functions as an integrator of diverse signaling, including transforming growth factor β signaling and the function of Smad3 is complexly regulated by differential phosphorylation at various sites of Smad3. Despite the importance of Smad3 and its various phosphoisoforms, their prognostic significance has rarely been studied. In this study, we demonstrated the prognostic significance of Smad3, its phosphoisoforms, and Smad4 expression by immunohistochemistry in 126 esophageal squamous cell carcinomas. The phosphoisoforms of Smad3 studied in this article included phosphorylation at C-terminal (pSmad3C)(Ser(423/425)) and phosphorylation at the linker region (pSmad3L)(Ser(213)). High expression of Smad3 was associated with shorter overall survival. Co-existence of high expression of pSmad3L(S213) and low expression of pSmad3C(S423/425) were associated with advanced N stage and an independent prognostic factor for overall [hazard ratio (HR) 2.03, 95 % confidence interval (CI) (1.10-3.75), p = 0.023] and disease-free survival [HR 2.41, 95 % CI (1.32-4.39), p = 0.004]. In conclusion, co-existence of high pSmad3L(Ser(213)) expression and low pSmad3C(Ser(423/425)) expression can be considered as immunohistochemical biomarkers for predicting prognosis as well as future therapeutic targets. In addition, our results of combinatory effect of differential phosphorylation of Smad3 on prognosis suggest the mode of action of Smad3 might be logically determined by its phosphorylation pattern. PMID:25267569

  19. Prognostic breast cancer signature identified from 3D culture model accurately predicts clinical outcome across independent datasets

    SciTech Connect

    Martin, Katherine J.; Patrick, Denis R.; Bissell, Mina J.; Fournier, Marcia V.

    2008-10-20

    One of the major tenets in breast cancer research is that early detection is vital for patient survival by increasing treatment options. To that end, we have previously used a novel unsupervised approach to identify a set of genes whose expression predicts prognosis of breast cancer patients. The predictive genes were selected in a well-defined three dimensional (3D) cell culture model of non-malignant human mammary epithelial cell morphogenesis as down-regulated during breast epithelial cell acinar formation and cell cycle arrest. Here we examine the ability of this gene signature (3D-signature) to predict prognosis in three independent breast cancer microarray datasets having 295, 286, and 118 samples, respectively. Our results show that the 3D-signature accurately predicts prognosis in three unrelated patient datasets. At 10 years, the probability of positive outcome was 52, 51, and 47 percent in the group with a poor-prognosis signature and 91, 75, and 71 percent in the group with a good-prognosis signature for the three datasets, respectively (Kaplan-Meier survival analysis, p<0.05). Hazard ratios for poor outcome were 5.5 (95% CI 3.0 to 12.2, p<0.0001), 2.4 (95% CI 1.6 to 3.6, p<0.0001) and 1.9 (95% CI 1.1 to 3.2, p = 0.016) and remained significant for the two larger datasets when corrected for estrogen receptor (ER) status. Hence the 3D-signature accurately predicts breast cancer outcome in both ER-positive and ER-negative tumors, though individual genes differed in their prognostic ability in the two subtypes. Genes that were prognostic in ER+ patients are AURKA, CEP55, RRM2, EPHA2, FGFBP1, and VRK1, while genes prognostic in ER patients include ACTB, FOXM1 and SERPINE2 (Kaplan-Meier p<0.05). Multivariable Cox regression analysis in the largest dataset showed that the 3D-signature was a strong independent factor in predicting breast cancer outcome. The 3D-signature accurately predicts breast cancer outcome across multiple datasets and holds prognostic

  20. [Prognostic significance of syncope in patients with Wolff-Parkinson-White syndrome].

    PubMed

    Auricchio, A; Klein, H; Trappe, H J; Troester, J

    1990-12-01

    The prognostic value of syncope in symptomatic patients with Wolff-Parkinson-White syndrome (WPW) is unknown. Therefore, in order to evaluate the sensibility, specificity, positive and negative predictive value of syncope and compare those values with the one obtained for the shortest RR interval (less than or equal to 250 msec) as well as for the anterograde refractory period of the accessory pathway (less than 270 msec), we reviewed the clinical and electrophysiological data of 158 symptomatic patients with WPW. Fourty-eight patients (30%) reported at least one episode of syncope, and 24 out of 158 patients experienced an aborted sudden death, probably due to rapid conduction via the accessory pathway during atrial fibrillation. Syncope has poor sensibility but high specificity in recognizing an aborted sudden death. However, the syncope demonstrated it had a lower prognostic value when compared with other electrophysiological parameters in correctly identifying patients with a history of ventricular tachycardia and/or fibrillation. In conclusion, the data of this study propose the symptom "syncope" as a frequent event in the history of symptomatic patients with WPW referred to electrophysiological study. Generally its presence does not correctly identify patients who experienced an aborted sudden death. Furthermore, its prognostic value is significantly lower than a shorter RR interval (less than or equal to 250 msec) during atrial fibrillation and an anterograde effective refractory period less than 270 msec. PMID:2083811

  1. Peripheral blood CD4/CD19 cell ratio is an independent prognostic factor in classical Hodgkin lymphoma.

    PubMed

    Gaudio, Francesco; Perrone, Tommasina; Mestice, Anna; Curci, Paola; Giordano, Annamaria; Delia, Mario; Pastore, Domenico; Specchia, Giorgina

    2014-07-01

    Classical Hodgkin lymphoma (cHL) is characterized by the presence of tumoral cells in a rich background of T and B cells, macrophages and other inflammatory cells. The contribution of these non-tumoral cells to the pathogenesis of HL is still poorly understood. In our study we evaluated the prognostic significance of peripheral blood B, T and natural killer (NK) cells at diagnosis in 118 immunocompetent patients with cHL treated at our institution between January 2006 and December 2010. Fifty-four (46%) were male and 64 (54%) female. Median age at diagnosis was 33 years (range 15-82), and 71 patients (60%) presented an advanced stage (IIB-IV), 54 (46%) had bulky disease and 55 (47%) presented B symptoms. At the end of treatment, 94 patients (80%) had a complete response (CR) and 24 (20%) had a partial response. After a median follow-up of 54 months, 18 patients (15%) had relapsed. The variables that had a negative impact on progression-free survival (PFS) at univariate analysis were advanced stage, bone marrow involvement, International Prognostic Score (IPS) ≥ 3, positive interim positron emission tomography (int-PET), NK cells < 200/μL, CD19 cells < 85/μL, CD3/CD19 ratio ≥ 13 and CD4/CD19 ratio ≥ 10. At multivariate analysis, advanced stage, positive int-PET and CD4/CD19 ratio ≥ 10 were independent prognostic factors of PFS. New biological markers could be predictive of the response to treatment and survival in cHL. A CD4/CD19 ratio ≥ 10 seems to be associated with a worse outcome. PMID:24164533

  2. Prognostic significance of discoidin domain receptor 2 (DDR2) expression in ovarian cancer

    PubMed Central

    Fan, Yi; Xu, Zhe; Fan, Jin; Huang, Liu; Ye, Ming; Shi, Kun; Huang, Zheng; Liu, Yaqiong; He, Langchi; Huang, Jiezhen; Wang, Yibin; Li, Qiufeng

    2016-01-01

    Increasing evidence has suggested that discoidin domain receptor 2 (DDR2) plays an important role in cancer development and metastasis. However, the correlation between DDR2 expression and clinical outcome in ovarian cancer has not been investigated. In this study, DDR2 expression was examined by Real-time PCR in surgically resected ovarian cancer and normal ovary tissues. Besides, DDR2 expression was analyzed immunohistochemically in 103 ovarian cancer patients, and the correlation between DDR2 expression with clinicopathologic factors was analyzed. The result showed that DDR2 mRNA expression was upregulated in ovarian cancer tissues compared with normal ovary tissues. Statistical analysis revealed that DDR2 expression correlated with tumor stage (P = 0.008) and peritoneal metastasis (P = 0.009). Patients with high DDR2 expression showed poorer 5-year overall survival (P = 0.005), and DDR2 remained an independent prognostic marker for OS (P = 0.013) in multivariate analysis. Our results suggest that DDR2 might be closely associated with ovarian cancer progression and metastasis. Its high expression may serve as a potential prognostic biomarker in human ovarian cancer. PMID:27398168

  3. The expression level of HJURP has an independent prognostic impact and predicts the sensitivity to radiotherapy in breast cancer

    SciTech Connect

    Hu, Zhi; Huang, Ge; Sadanandam, Anguraj; Gu, Shenda; Lenburg, Marc E; Pai, Melody; Bayani, Nora; Blakely, Eleanor A; Gray, Joe W; Mao, Jian-Hua

    2010-06-25

    Introduction: HJURP (Holliday Junction Recognition Protein) is a newly discovered gene reported to function at centromeres and to interact with CENPA. However its role in tumor development remains largely unknown. The goal of this study was to investigate the clinical significance of HJURP in breast cancer and its correlation with radiotherapeutic outcome. Methods: We measured HJURP expression level in human breast cancer cell lines and primary breast cancers by Western blot and/or by Affymetrix Microarray; and determined its associations with clinical variables using standard statistical methods. Validation was performed with the use of published microarray data. We assessed cell growth and apoptosis of breast cancer cells after radiation using high-content image analysis. Results: HJURP was expressed at higher level in breast cancer than in normal breast tissue. HJURP mRNA levels were significantly associated with estrogen receptor (ER), progesterone receptor (PR), Scarff-Bloom-Richardson (SBR) grade, age and Ki67 proliferation indices, but not with pathologic stage, ERBB2, tumor size, or lymph node status. Higher HJURP mRNA levels significantly decreased disease-free and overall survival. HJURP mRNA levels predicted the prognosis better than Ki67 proliferation indices. In a multivariate Cox proportional-hazard regression, including clinical variables as covariates, HJURP mRNA levels remained an independent prognostic factor for disease-free and overall survival. In addition HJURP mRNA levels were an independent prognostic factor over molecular subtypes (normal like, luminal, Erbb2 and basal). Poor clinical outcomes among patients with high HJURP expression werevalidated in five additional breast cancer cohorts. Furthermore, the patients with high HJURP levels were much more sensitive to radiotherapy. In vitro studies in breast cancer cell lines showed that cells with high HJURP levels were more sensitive to radiation treatment and had a higher rate of apoptosis

  4. Upregulation of nemo-like kinase is an independent prognostic factor in colorectal cancer

    PubMed Central

    Zhang, Wei; He, Jian; Du, Yan; Gao, Xian-Hua; Liu, Yan; Liu, Qi-Zhi; Chang, Wen-Jun; Cao, Guang-Wen; Fu, Chuan-Gang

    2015-01-01

    AIM: To investigate the expression and oncogenic role of nemo-like kinase (NLK) in colorectal cancer. METHODS: Expression of NLK protein was assessed by immunohistochemistry in tissue specimens from 56 cases of normal colorectal mucosa, 51 cases of colorectal adenoma, and 712 cases of colorectal cancer. In addition, NLK expression was knocked down using a lentivirus carrying NLK small hairpin RNA in colorectal cancer cells. Cell viability methylthiazoletetrazolium assays, colony formation assays, flow cytometry cell cycle assays, Transwell migration assays, and gene expression assays were performed to explore its role on proliferation and migration of colorectal cancer. RESULTS: Expression of NLK protein progressively increased in tissues from the normal mucosa through adenoma to various stages of colorectal cancer. Overexpression of NLK protein was associated with advanced tumor-lymph node-metastasis stages, poor differentiation, lymph node and distant metastases, and a higher recurrence rate of colorectal cancer (P < 0.05). Multivariate analyses showed that NLK expression was an independent prognostic factor to predict overall survival (hazard ratio 2.57, 95% confidence interval: 1.66-3.98; P < 0.001) and disease-free survival (hazard ratio 1.96, 95% confidence interval: 1.40-2.74: P < 0.001) of colorectal cancer patients. Furthermore, knockdown of NLK expression in colorectal cancer cell lines reduced cell viability, colony formation, and migration, and arrested tumor cells at the G0/G1 phase of the cell cycle. At the gene level, knockdown of NLK expression inhibited matrix metalloproteinase-2 expression in colorectal cancer cells. CONCLUSION: NLK overexpression is an independent prognostic factor in colorectal cancer and knockdown of NLK expression inhibits colorectal cancer progression and metastasis. PMID:26269673

  5. The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia

    PubMed Central

    Ouillette, Peter; Collins, Roxane; Shakhan, Sajid; Li, Jinghui; Li, Cheng; Shedden, Kerby; Malek, Sami N.

    2011-01-01

    Purpose To further our understanding of the biology and prognostic significance of various chromosomal 13q14 deletions in CLL. Experimental Design We have analyzed data from SNP 6.0 arrays to define the anatomy of various 13q14 deletions in a cohort of 255 CLL patients and have correlated two subsets of 13q14 deletions (type I: exclusive of RB1 and type II: inclusive of RB1) with patient survival. Further, we have measured the expression of the 13q14-resident microRNAs by Q-PCR in 242 CLL patients and subsequently assessed their prognostic significance. We have sequenced all coding exons of RB1 in patients with monoallelic Rb1 deletion and have sequenced the 13q14-resident miR locus in all patients. Results Large 13q14 (type II) deletions were detected in ~20% of all CLL patients and were associated with shortened survival. A strong association between 13q14 type II deletions and elevated genomic complexity, as measured through CLL-FISH or SNP 6.0 array profiling, was identified, suggesting that these lesions may contribute to CLL disease evolution through genomic destabilization. Sequence and copy number analysis of the RB1 gene identified a small CLL subset that is RB1 null. Finally, neither the expression levels of the 13q14-resident microRNAs nor the degree of 13q14 deletion, as measured through SNP 6.0 array-based copy number analysis, had significant prognostic importance. Conclusions Our data suggest that the clinical course of CLL is accelerated in patients with large (type II) 13q14 deletions that span the RB1 gene, therefore justifying routine identification of 13q14 subtypes in CLL management. PMID:21890456

  6. Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma.

    PubMed

    Jin, Haojie; Zhang, Yurong; You, Haiyan; Tao, Xuemei; Wang, Cun; Jin, Guangzhi; Wang, Ning; Ruan, Haoyu; Gu, Dishui; Huo, Xisong; Cong, Wenming; Qin, Wenxin

    2015-01-01

    Kynurenine 3-monooxygenase (KMO) is a pivotal enzyme in the kynurenine pathway of tryptophan degradation and plays a critical role in Huntington's and Alzheimer's diseases. This study aimed to examine the expression of KMO in human hepatocellular carcinoma (HCC) and investigate the relationship between its expression and prognosis of HCC patients. We first analyzed KMO expression in 120 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), and 205 clinical HCC specimens using immunohistochemistry (IHC). Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. The results of IHC analysis showed that KMO expression was significantly higher in HCC tissues than that in normal liver tissues (all p < 0.05). Survival and recurrence analyses showed that KMO was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR) (both p<0.01). And in vitro studies revealed that KMO positively regulated proliferation, migration, and invasion of HCC cells. These results suggest that KMO exhibits tumor-promoting effects towards HCC and it may serve as a novel prognostic marker in HCC. PMID:26099564

  7. Prognostic significance of carcinoembryonic antigen in colorectal carcinoma. Serum levels before and after resection and before recurrence.

    PubMed

    Chu, D Z; Erickson, C A; Russell, M P; Thompson, C; Lang, N P; Broadwater, R J; Westbrook, K C

    1991-03-01

    The use of carcinoembryonic antigen was evaluated in 425 patients with a mean follow-up of 48 months. The preoperative and postoperative carcinoembryonic antigen levels were predictive of recurrence and survival independent of the tumor stage. In a multivariate regression analysis of age, location, tumor stage, and preoperative and postoperative carcinoembryonic antigen levels, the latter three factors were significant prognostic variables with respect to the adjusted survival. Recurrent disease was found in 42% of patients, excluding patients with stage IV disease. The carcinoembryonic antigen level at recurrence was greater than 5 ng/mL in 79% of the patients and in 89% of the intra-abdominal recurrences. Carcinoembryonic antigen level at recurrence was not predictive of postrecurrence survival except in the subgroup of locoregional disease. The life span in patients with liver and lung metastases was not influenced by carcinoembryonic antigen level at recurrence. Preoperative and postoperative carcinoembryonic antigen levels can indicate a poorer prognostic group of patients with colorectal cancer who may benefit from adjuvant treatment. The carcinoembryonic antigen at recurrence can be used effectively to diagnose intra-abdominal recurrences and project survival after development of local/regional disease. PMID:1998473

  8. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma

    PubMed Central

    Hedner, Charlotta; Borg, David; Nodin, Björn; Karnevi, Emelie; Jirström, Karin; Eberhard, Jakob

    2016-01-01

    Background Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR) and 3 (HER3), as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma. Methods Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology. Results and Discussion High EGFR expression was an independent risk factor for shorter overall survival (OS), whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods. PMID:26844548

  9. Prognostic significance of two lipid metabolism enzymes, HADHA and ACAT2, in clear cell renal cell carcinoma.

    PubMed

    Zhao, Zuohui; Lu, Jiaju; Han, Liping; Wang, Xiaoqing; Man, Quanzhan; Liu, Shuai

    2016-06-01

    Renal cell carcinoma (RCC) is one of the leading causes of cancer mortality in adults, but there is still no acknowledged biomarker for its prognostic evaluation. Our previous proteomic data had demonstrated the dysregulation of some lipid metabolism enzymes in clear cell RCC (ccRCC). In the present study, we elucidated the expression of two lipid metabolism enzymes, hydroxyl-coenzyme A dehydrogenase, alpha subunit (HADHA) and acetyl-coenzyme A acetyltransferase 2 (ACAT2), using Western blotting analysis, then assessed the prognostic potential of HADHA and ACAT2 using immunohistochemistry (IHC) on a tissue microarray of 145 ccRCC tissues. HADHA and ACAT2 were downregulated in ccRCC (P < 0.05); further IHC analysis revealed that HADHA expression was significantly associated with tumor grade, stage, size, metastasis, and cancer-specific survival (P = 0.004, P < 0.001, P < 0.001, P = 0.049, P < 0.001, respectively) and ACAT2 expression was significantly associated with tumor stage, size, and cancer-specific survival (P < 0.001, P = 0.001, P < 0.001, respectively). In addition, a strong correlation was found between HADHA and ACAT2 expression (R = 0.655, P < 0.001). Further univariate survival analysis demonstrated that high stage, big tumor size, metastasis, and HADHA and ACAT2 down-expression were associated with poorer prognosis on cancer-specific survival (P = 0.007, P = 0.005, P = 0.006, P < 0.001, P = 0.001, respectively), and multivariate analysis revealed that HADHA, stage, and metastasis were identified as independent prognostic factors for cancer-specific survival in patients with ccRCC (P = 0.018, P = 0.046, P = 0.001, respectively). Collectively, these findings indicated that HADHA could serve as a promising prognostic marker in ccRCC, which indicated lipid metabolism abnormality might be involved in ccRCC tumorigenesis. PMID:26715271

  10. Prognostic Significance of Invasive Tumor Front in Oral Squamous Cell Carcinoma.

    PubMed

    Patil, Shankargouda; Augustine, Dominic; Rao, Roopa S

    2016-01-01

    Tumor, Node, and Metastasis (TNM) classification dictates treatment planning for oral squamous cell carcinoma (OSCC). This system stages tumor on the principle that smaller size tumors have a better prognosis than larger tumors with local or distant spread. It has been brought to light that many tumors with similar clinical staging show different clinical behavior and growth patterns. This results in difficulty in predicting the prognosis for patients with OSCC on the basis of clinical staging alone.(1) How to cite this article: Patil S, Augustine D, Rao RS. Prognostic Significance of Invasive Tumor Front in Oral Squamous Cell Carcinoma. J Contemp Dent Pract 2016;17(1):1-2. PMID:27084854

  11. Prognostic significance of adverse events in patients with hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Granito, Alessandro; Marinelli, Sara; Negrini, Giulia; Menetti, Saverio; Benevento, Francesca; Bolondi, Luigi

    2016-01-01

    Sorafenib is the standard treatment for patients with hepatocellular carcinoma (HCC) with advanced stage disease. Although its effectiveness has been demonstrated by randomized clinical trials and confirmed by field practice studies, reliable markers predicting therapeutic response have not yet been identified. Like other tyrosine kinase inhibitors, treatment with sorafenib is burdened by the development of adverse effects, the most frequent being cutaneous toxicity, diarrhoea, arterial hypertension and fatigue. In recent years, several studies have analysed the correlation between off-target effects and sorafenib efficacy in patients with HCC. In this review, an overview of the studies assessing the prognostic significance of sorafenib-related adverse events is provided. PMID:26929785

  12. The Prognostic Significance of the Hedgehog Signaling Pathway in Colorectal Cancer.

    PubMed

    Papadopoulos, Vassilis; Tsapakidis, Konstantinos; Riobo Del Galdo, Natalia A; Papandreou, Christos N; Del Galdo, Francesco; Anthoney, Alan; Sakellaridis, Nikos; Dimas, Konstantinos; Kamposioras, Konstantinos

    2016-06-01

    Despite significant advances in the management of colorectal cancer (CRC) the identification of new prognostic biomarkers continues to be a challenge. Since its initial discovery, the role of the Hedgehog (Hh) signaling pathway in carcinogenesis has been extensively studied. We herein review and comment on the prognostic significance of the Hh signaling pathway in CRC. The differential expression of Hh pathway components between malignant and nonmalignant conditions as well as correlation of Hh activation markers with various clinicopathological parameters and the effect on disease-free survival, overall survival, and disease recurrence in patients with CRC is summarized and discussed. According to the studies reviewed herein the activation of the Hh pathway seems to be correlated with adverse clinicopathological features and worse survival. However, to date study results show significant variability with regard to the effect on outcomes. Such results need to be interpreted carefully and emphasize the need for further well designed studies to characterize the actual influence of the Hh pathway in CRC prognosis. PMID:27032873

  13. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer.

    PubMed

    Kolin, David L; Sy, Keiyan; Rotondo, Fabio; Bassily, Mena N; Kovacs, Kalman; Brezden-Masley, Christine; Streutker, Catherine J; Yousef, George M

    2014-09-01

    The prognosis of patients following surgery for gastric cancer is often poor and is estimated using traditional clinicopathological parameters, which can be inaccurate predictors of future survival. Kallikreins are a group of serine proteases, which are differentially expressed in many human tumors and are being investigated as potential cancer biomarkers. This study assessed the prognostic utility of human tissue kallikrein-like peptidases 6 and 10 (KLK6 and KLK10) and correlated their expression with histopathological and clinical parameters in gastric cancer. We constructed a gastric tumor tissue microarray from 113 gastrectomy specimens and quantified KLK6 and KLK10 expression using immunohistochemistry. To overcome the problem of inter-observer variability and subjectivity in immunohistochemistry interpretation, a whole-slide scanned image of the tissue microarray was analyzed using an automated algorithm to quantify staining intensity. KLK6 expression was positively correlated with nodal involvement (p=0.002) and was predictive of advanced-stage disease (p<0.05). Kaplan-Meier survival curves revealed that tumors expressing high levels of KLK6 were significantly associated with significantly lower overall survival (p=0.04). KLK10 overexpression was also a predictor of advanced-stage disease (p<0.01), but was not significantly correlated with lymph node involvement or survival period. Our results show the potential ability of KLK6 as a prognostic marker for gastric cancer. PMID:25153389

  14. Prognostic and Clinicopathological Significance of Transducer-Like Enhancer of Split 1 Expression in Gastric Cancer

    PubMed Central

    Lee, Ji-Hye; Son, Myoung-Won; Kim, Kyung-Ju; Oh, Mee-Hye; Cho, Hyundeuk; Lee, Hyun Ju; Jang, Si-Hyong

    2016-01-01

    Purpose Transducer-like enhancer of split 1 (TLE1) is a member of the Groucho/TLE family of transcriptional co-repressors that regulate the transcriptional activity of numerous genes. TLE1 is involved in the tumorigenesis of various tumors. We investigated the prognostic significance of TLE1 expression and its association with clinicopathological parameters in gastric cancer (GC) patients. Materials and Methods Immunohistochemical analysis of six tissue microarrays was performed to examine TLE1 expression using 291 surgically resected GC specimens from the Soonchunhyang University Cheonan Hospital between July 2006 and December 2009. Results In the non-neoplastic gastric mucosa, TLE1 expression was negative. In GC, 121 patients (41.6%) were positive for TLE1. The expression of TLE1 was significantly associated with male gender (P=0.021), less frequent lymphatic (P=0.017) or perineural invasion (P=0.029), intestinal type according to the Lauren classification (P=0.024), good histologic grade (P<0.001), early pathologic T-stage (P=0.012), and early American Joint Committee on Cancer stage (P=0.022). In the Kaplan-Meier analysis, the TLE1 expression was significantly associated with longer disease-free (P=0.022) and overall (P=0.001) survival rates. Conclusions We suggested that TLE1 expression is a good prognostic indicator in GCs. PMID:27104023

  15. The Expression and Prognostic Significance of Retinoic Acid Metabolising Enzymes in Colorectal Cancer

    PubMed Central

    Brown, Gordon T.; Cash, Beatriz Gimenez; Blihoghe, Daniela; Johansson, Petronella; Alnabulsi, Ayham; Murray, Graeme I.

    2014-01-01

    significantly associated with prognosis both in the total cohort and in those tumours which are mismatch repair proficient. CYP26B1 was independently prognostic in a multivariate model both in the whole patient cohort (HR = 1.177, 95%CI = 1.020–1.216, p = 0.026) and in mismatch repair proficient tumours (HR = 1.255, 95%CI = 1.073–1.467, p = 0.004). PMID:24608339

  16. Stromal CD4/CD25 positive T-cells are a strong and independent prognostic factor in non-small cell lung cancer patients, especially with adenocarcinomas.

    PubMed

    Kayser, Gian; Schulte-Uentrop, Luzie; Sienel, Wulf; Werner, Martin; Fisch, Paul; Passlick, Bernward; Zur Hausen, Axel; Stremmel, Christian

    2012-06-01

    Within the concert of immune reactions against tumour cells cytotoxic and regulatory T-cells are of utmost importance. Several studies revealed contradictory results on this issue. We therefore focused on functional expression patterns and localization of tumour-infiltrating T-lymphocytes in non-small cell lung cancer (NSCLC) and their impact on patient's survival. 232 curatively operated NSCLC patients were included. After histological reevaluation and construction of tissue-multi-arrays immunohistochemical doublestains for CD3/CD8 and CD4/CD25 were performed to evaluate the total number of T-cells and their subsets of cytotoxic and activated T-cells. Additionally, the localization of the lymphocytes was included in the analysis. Hereby, T-cells within the tumour stroma were regarded as stromal, those among cancer cells as intraepithelial. The number of lymphocytes differed significantly between the histological subtypes being most prominent in large cell carcinomas. Survival analysis showed that high numbers of stromal T-lymphocytes are of beneficial prognostic influence in NSCLC patients. This also proved to be an independent prognostic factor in adenocarcinomas. Thus, in a large and well characterized cohort of NSCLC this is the first study to determine the prognostic value of stromal T-lymphocytes, as these are an independent prognosticator in NSCLC especially in adenocarcinomas whereas intraepithelial T-cells are not. PMID:22300751

  17. miR-422a is an independent prognostic factor and functions as a potential tumor suppressor in colorectal cancer

    PubMed Central

    Zheng, Gui-Xi; Qu, Ai-Lin; Yang, Yong-Mei; Zhang, Xin; Zhang, Shou-Cai; Wang, Chuan-Xin

    2016-01-01

    AIM: To determine the expression of miR-422a in colorectal cancer (CRC) tissues and to further explore the prognostic value and function of miR-422a in CRC carcinogenesis. METHODS: miR-422a expression was analyzed in 102 CRC tissues and paired normal mucosa adjacent to carcinoma by quantitative real-time PCR. The relationship of miR-422a expression with clinicopathological parameters was also analyzed. Kaplan-Meier analysis and Cox multivariate analysis were performed to estimate the potential role of miR-422a. Cell proliferation, migration, and invasion were used for in vitro functional analysis of miR-422a. RESULTS: The levels of miR-422a were dramatically reduced in CRC tissues compared with normal mucosa (P < 0.05), and significantly correlated with local invasion (P = 0.004) and lymph node metastasis (P < 0.001). Kaplan-Meier survival and Cox regression multivariate analyses revealed that miR-422a expression (HR = 0.568, P = 0.015) and clinical TNM stage (HR = 2.942, P = 0.003) were independent prognostic factors for overall survival in CRC patients. Furthermore, in vitro experiments showed that overexpression of miR-422a inhibited the proliferation, migration, and invasion of SW480 and HT-29 cells. CONCLUSION: Down-regulation of miR-422a may serve as an independent prognosis factor in CRC. MiR-422a functions as a tumor suppressor and regulates progression of CRC. PMID:27350737

  18. Lack of prognostic significance of adiponectin immunohistochemical expression in patients with triple-negative breast cancer

    PubMed Central

    Olmez, Omer Fatih; Kanat, Ozkan; Kabul, Selva; Canhoroz, Mustafa; Avci, Nilufer; Hartavi, Mustafa; Deligonul, Adem; Çubukçu, Sinem; Manavoglu, Osman

    2014-01-01

    Introduction Triple-negative breast cancers (TNBCs) – which lack the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) – have no established markers that can be used for prognostic stratification. As adiponectin has been previously implicated in a more aggressive phenotype of primary breast cancer, we explored the relation between adiponectin immunohistochemical expression and prognosis in TNBCs. Material and methods Immunohistochemical staining for adiponectin was performed in 38 TNBC patients. Disease-free survival (DFS) and overall survival (OS) served as the main outcome measures. Results Of the 38 TNBC patients, 18 (47%) had negative and 20 (53%) positive adiponectin immunohistochemical expression. We did not find any significant association between adiponectin immunohistochemical expression and the baseline characteristics. In addition, there were no associations between adiponectin immunohistochemical expression and prognosis. Conclusions Although our results suggest that adiponectin immunohistochemical expression is not of prognostic significance in TNBCs, further studies are warranted to determine the role of this adipokine in breast cancer biology. PMID:24876819

  19. Prognostic significance of CpG island methylator phenotype in surgically resected small cell lung carcinoma.

    PubMed

    Saito, Yuichi; Nagae, Genta; Motoi, Noriko; Miyauchi, Eisaku; Ninomiya, Hironori; Uehara, Hirofumi; Mun, Mingyon; Okumura, Sakae; Ohyanagi, Fumiyoshi; Nishio, Makoto; Satoh, Yukitoshi; Aburatani, Hiroyuki; Ishikawa, Yuichi

    2016-03-01

    Methylation is closely involved in the development of various carcinomas. However, few datasets are available for small cell lung cancer (SCLC) due to the scarcity of fresh tumor samples. The aim of the present study is to clarify relationships between clinicopathological features and results of the comprehensive genome-wide methylation profile of SCLC. We investigated the genome-wide DNA methylation status of 28 tumor and 13 normal lung tissues, and gene expression profiling of 25 SCLC tissues. Following unsupervised hierarchical clustering and non-negative matrix factorization, gene ontology analysis was performed. Clustering of SCLC led to the important identification of a CpG island methylator phenotype (CIMP) of the tumor, with a significantly poorer prognosis (P = 0.002). Multivariate analyses revealed that postoperative chemotherapy and non-CIMP were significantly good prognostic factors. Ontology analyses suggested that the extrinsic apoptosis pathway was suppressed, including TNFRSF1A, TNFRSF10A and TRADD in CIMP tumors. Here we revealed that CIMP was an important prognostic factor for resected SCLC. Delineation of this phenotype may also be useful for the development of novel apoptosis-related chemotherapeutic agents for treatment of the aggressive tumor. PMID:26748784

  20. Classical and Novel Prognostic Markers for Breast Cancer and their Clinical Significance

    PubMed Central

    Taneja, Pankaj; Maglic, Dejan; Kai, Fumitake; Zhu, Sinan; Kendig, Robert D.; Fry, Elizabeth A.; Inoue, Kazushi

    2010-01-01

    The use of biomarkers ensures breast cancer patients receive optimal treatment. Established biomarkers such as estrogen receptor (ER) and progesterone receptor (PR) have been playing significant roles in the selection and management of patients for endocrine therapy. HER2 is a strong predictor of response to trastuzumab. Recently, the roles of ER as a negative and HER2 as a positive indicator for chemotherapy have been established. Ki67 has traditionally been recognized as a poor prognostic factor, but recent studies suggest that measurement of Ki67-positive cells during treatment will more effectively predict treatment efficacy for both anti-hormonal and chemotherapy. p53 mutations are found in 20–35% of human breast cancers and are associated with aggressive disease with poor clinical outcome when the DNA-binding domain is mutated. The utility of cyclin D1 as a predictor of breast cancer prognosis is controversial, but cyclin D1b overexpression is associated with poor prognosis. Likewise, overexpression of the low molecular weight form of cyclin E1 protein predicts poor prognosis. Breast cancers from BRCA1/2 carriers often show high nuclear grades, negativity to ER/PR/HER2, and p53 mutations, and thus, are associated with poor prognosis. The prognostic values of other molecular markers, such as p14ARF, TBX2/3, VEGF in breast cancer are also discussed. Careful evaluation of these biomarkers with current treatment modality is required to determine whether their measurement or monitoring offer significant clinical benefits. PMID:20567632

  1. Prognostic significance of the lymphocyte-to-monocyte ratio in patients with metastatic colorectal cancer

    PubMed Central

    Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Ohtani, Hiroshi; Sakurai, Katsunobu; Yamazoe, Sadaaki; Kimura, Kenjiro; Toyokawa, Takahiro; Amano, Ryosuke; Tanaka, Hiroaki; Muguruma, Kazuya; Hirakawa, Kosei

    2015-01-01

    AIM: To evaluate the prognostic significance of the lymphocyte to monocyte ratio (LMR) in patients with unresectable metastatic colorectal cancer who received palliative chemotherapy. METHODS: A total of 104 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy were enrolled. The LMR was calculated from blood samples by dividing the absolute lymphocyte count by the absolute monocyte count. Pre-treatment LMR values were measured within one week before the initiation of chemotherapy, while post-treatment LMR values were measured eight weeks after the initiation of chemotherapy. RESULTS: The median pre-treatment LMR was 4.16 (range: 0.58-14.06). We set 3.38 as the cut-off level based on the receiver operating characteristic curve. Based on the cut-off level of 3.38, 66 patients were classified into the high pre-treatment LMR group and 38 patients were classified into the low pre-treatment LMR group. The low pre-treatment LMR group had a significantly worse overall survival rate (P = 0.0011). Moreover, patients who demonstrated low pre-treatment LMR and normalization after treatment exhibited a better overall survival rate than the patients with low pre-treatment and post-treatment LMR values. CONCLUSION: The lymphocyte to monocyte ratio is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy. PMID:26379401

  2. Prognostic significance of periodic acid-Schiff-positive patterns in primary cutaneous melanoma.

    PubMed

    Warso, M A; Maniotis, A J; Chen, X; Majumdar, D; Patel, M K; Shilkaitis, A; Gupta, T K; Folberg, R

    2001-03-01

    The patterns of periodic acid-Schiff (PAS) staining of extracellular matrix in histological sections of certain melanomas may be predictive of outcome. Recent in vitro and molecular genetic data suggest that the appearance of these patterns in both uveal and cutaneous melanoma is a function of aggressive tumor cells. We studied 96 patients with primary cutaneous melanomas treated at the University of Illinois at Chicago who were monitored for disease-free survival. Survival probabilities were determined by Kaplan-Meier estimates, and prognostic factors were evaluated by multivariate analysis. By univariate analysis, there was a significant decrease in disease-free survival among patients whose tumors contained parallel with cross-linking or network patterns (PXNs; P = 0.0070). Stepwise regression with Cox models that included the combinations of the PAS-positive patterns, tumor thickness, female gender, ulceration, and age yielded a model with thickness and the PAS-positive parallel with cross-linking or networks. Despite the relatively small sample size in this study, the detection of the PAS-positive parallel with cross-linking or networking in cutaneous melanoma was associated with a decrease in disease-free outcome. Additional studies of the prognostic significance of these patterns is warranted on larger data sets. PMID:11297236

  3. Occurrence and prognostic significance of cytogenetic evolution in patients with multiple myeloma

    PubMed Central

    Binder, M; Rajkumar, S V; Ketterling, R P; Dispenzieri, A; Lacy, M Q; Gertz, M A; Buadi, F K; Hayman, S R; Hwa, Y L; Zeldenrust, S R; Lust, J A; Russell, S J; Leung, N; Kapoor, P; Go, R S; Gonsalves, W I; Kyle, R A; Kumar, S K

    2016-01-01

    Cytogenetic evaluation at the time of diagnosis is essential for risk stratification in multiple myeloma, however little is known about the occurrence and prognostic significance of cytogenetic evolution during follow-up. We studied 989 patients with multiple myeloma, including 304 patients with at least two cytogenetic evaluations. Multivariable-adjusted regression models were used to assess the associations between the parameters of interest and cytogenetic evolution as well as overall survival. The prognostic significance of baseline cytogenetic abnormalities was most pronounced at the time of diagnosis and attenuated over time. In the patients with serial cytogenetic evaluations, the presence of t(11;14) at the time of diagnosis was associated with decreased odds of cytogenetic evolution during follow-up (odds ratio (OR)=0.22, 95% confidence interval (CI)=0.09–0.56, P=0.001), while the presence of at least one trisomy or tetrasomy was associated with increased odds (OR=2.96, 95% CI=1.37–6.42, P=0.006). The development of additional abnormalities during the 3 years following diagnosis was associated with increased subsequent mortality (hazard ratio=3.31, 95% CI=1.73–6.30, P<0.001). These findings emphasize the importance of the underlying clonal disease process for risk assessment and suggest that selected patients may benefit from repeated risk stratification. PMID:26967818

  4. Prognostic and Clinicopathological Significance of Survivin in Colorectal Cancer: A Meta-Analysis

    PubMed Central

    Krieg, Andreas; Werner, Thomas A.; Verde, Pablo E.; Stoecklein, Nikolas H.; Knoefel, Wolfram T.

    2013-01-01

    Survivin/BIRC5 is a potentially interesting prognostic marker and therapeutic target in colorectal cancer (CRC). However, the available data on survivin expression in CRC are heterogeneous. Thus, to clarify the prognostic relevance of survivin in patients with CRC and its association with clinicopathological parameters we performed a meta-analysis. We screened PubMed and EMBASE for those studies that investigated the prognostic value of survivin and its association with clinicopathological parameters in CRC. Data from eligible studies were extracted and included into the meta-analyses using a random effects model. Electronical literature search identified 15 studies including 1934 patients with CRC mostly detecting survivin by immunohistochemistry (IHC). Pooled hazard ratios of 11 studies that performed survival analysis revealed a positive correlation between survivin expression and poor prognosis (HR 1.93; 95% CI: 1.55–2.42; P<0.00001; I2 = 23%). Subgroup analyses with respect to the detection method, HR estimation, global quality score and the country of origin in which the study was conducted supported the stability of this observation. In addition, meta-analyses revealed a significant association between expression of survivin and the presence of lymph node metastases (OR: 0.37; 95% CI: 0.19–0.75; I2 = 61%) or blood vessel invasion (OR: 0.50; 95% CI: 0.28–0.90; I2 = 0%). Expression of survivin indicates poor prognosis and a pro-metastatic phenotype and may be useful in identifying a subgroup of patients that could benefit from a targeted therapy against survivin in CRC. PMID:23755220

  5. Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia

    PubMed Central

    Sarris, Katerina; Koulieris, Efstathios; Bartzis, Vassiliki; Tzenou, Tatiana; Sachanas, Sotirios; Nikolaou, Eftychia; Efthymiou, Anna; Bitsani, Katerina; Dimou, Maria; Vassilakopoulos, Theodoros P.; Angelopoulou, Maria K.; Kontopidou, Flora; Tsaftaridis, Panagiotis; Kafasi, Nikolitsa; Pangalis, Gerasimos A.; Panayiotidis, Panayiotis P.; Harding, Stephen

    2013-01-01

    Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients. Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients' series. Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients' followup was 32 months (range 4–228). Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P = 0.0005 and P = 0.000003, resp.) and overall survival (P = 0.05 and P = 0.003, resp.). They also correlated with β2-microglobulin (P = 0.009 and P = 0.03, resp.), serum albumin (P = 0.009 for summated sFLC), hemoglobin (P < 0.001), abnormal LDH (P = 0.037 and P = 0.001, resp.), Binet stage (P < 0.05) and with the presence of beta symptoms (P = 0.004 for summated sFLC). Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters. PMID:24288537

  6. Prevalence of renal artery disease and its prognostic significance in patients undergoing coronary bypass grafting.

    PubMed

    Aboyans, Victor; Tanguy, Benedicte; Desormais, Ileana; Bonnet, Vincent; Chonchol, Michel; Laskar, Marc; Mohty, Dania; Lacroix, Philippe

    2014-10-01

    Several studies demonstrated the prognostic importance of renal failure and peripheral artery disease in patients undergoing coronary artery bypass grafting (CABG), but data regarding the prognostic value of renal artery disease in this context are scarce. We aimed to study the prevalence and prognostic value of renal artery disease in patients undergoing CABG. We assessed by duplex ultrasound the renal arteries of 429 consecutive patients who underwent CABG, of whom 401 had satisfactory imaging quality to detect >60% renal artery stenosis (RAS) and/or an elevated resistive index (ERI>0.80). Of the 401 subjects included (age 68±10 years, 83% men), 40 (10%) had RAS and 35 (9%) had ERI. Nine patients (2.2%) had both conditions. Patients were followed up for 12.4±7.0 months. The primary outcome was composite, including 30-day death, stroke, and/or myocardial infarction. In a multivariate model adjusted for age, gender, cardiovascular (CV) risk factors, renal function, chronic obstructive pulmonary disease, the use of off-pump CABG, CV co-morbidities, and drugs, the presence of ERI was strongly associated with the occurrence of the composite outcome (odds ratio 4.3, 95% confidence interval 1.7 to 9.9, p=0.0006). Similarly, ERI, not RAS, was significantly associated with the 30-day acute kidney disease and the midterm mortality, as well as fatal and nonfatal CV events. In conclusion, regardless of renal function and other factors, the renal resistive index is a strong predictor of CV and renal events after CABG. Renal duplex ultrasound can identify a subgroup of patients at high risk of CABG. PMID:25150754

  7. CEA Level, Radical Surgery, CD56 and CgA Expression Are Prognostic Factors for Patients With Locoregional Gastrin-Independent GNET

    PubMed Central

    Li, Yuan; Bi, Xinyu; Zhao, Jianjun; Huang, Zhen; Zhou, Jianguo; Li, Zhiyu; Zhang, Yefan; Li, Muxing; Chen, Xiao; Hu, Xuhui; Chi, Yihebali; Zhao, Dongbing; Zhao, Hong; Cai, Jianqiang

    2016-01-01

    Abstract Gastrin-independent gastric neuroendocrine tumors (GNETs) are highly malignant. Radical resections and lymphadenectomy are considered to be the only possible curative treatment for these tumors. However, the prognosis of gastrin-independent GNETs is not well defined. In this study, we identified prognostic factors of locoregional gastrin-independent GNETs. All patients diagnosed with locoregional gastrin-independent GNETs between 2000 and 2014 were included in this retrospective study. Clinical characteristics, blood tests, pathological characteristics, treatments, and follow-up data of the patients were collected and analyzed. Of the 66 patients diagnosed with locoregional gastrin-independent GNETs, 57 (86.4%) received radical resections, 7 (10.6%) with palliative resection, 1 (1.5%) with gastrojejunostomy, and 1 (1.5%) with exploration surgeries. The median survival time for these patients was 19.0 months (interquartile range, 11.0–38.0). The 1-, 3-, and 5-year survival rates were 72%, 34%, and 28%, respectively. Multivariate analysis indicated that carcinoembryonic antigen (CEA) level (P = 0.04), radical resection (P = 0.04), and positive Cluster of Differentiation 56 (CD56) expression (P = 0.016) were significant prognostic factors on overall survival rate. Further univariate and multivariate analysis of 57 patients who received radical resections found that CgA expression (P = 0.35) and CEA level (P = 0.33) are independent prognostic factors. Gastrin-independent GNETs had poor prognosis. Serum CEA level, radical surgery, CD56 and CgA expression are markers to evaluate the survival of patients with locoregional gastrin-independent GNETs. PMID:27149478

  8. Prognostic significance of pretreated serum lactate dehydrogenase level in nasopharyngeal carcinoma among Chinese population

    PubMed Central

    Zhang, Mingwei; Wei, Shushan; Su, Li; Lv, Wenlong; Hong, Jinsheng

    2016-01-01

    Abstract Background: A large number of studies have investigated the prognostic value of pretreated lactate dehydrogenase (LDH) level in nasopharyngeal carcinoma (NPC) patients while the role of it was inconsistent and inconclusive. Hence, the aim of the current study was to conduct a meta-analysis of all published studies to quantify the prognostic impact of pretreated serum LDH in NPC for Chinese population. Objectives: The aim of the current study was to conduct a meta-analysis of all published studies to quantify the prognostic impact of pretreated serum lactate dehydrogenase (LDH) in nasopharyngeal carcinoma (NPC) for Chinese population. Methods: The PubMed, Medline, Embase, and Web of Science databases were searched for studies that assessed survival outcome and LDH in NPC. Overall survival (OS) was the primary survival outcome. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were secondary outcomes. The pooled hazard ratios (HRs), associated with 95% confidence intervals (95% CIs), were combined to calculate overall effects. The Cochran Q and I2 statistics were used to assess heterogeneity. When apparent heterogeneity was observed, sensitivity and meta-regression analyses were performed to explore its origin. Results: Sixteen studies, which included 14,803 patients, were enrolled in the current meta-analysis to yield statistics. Overall, the pooled HR for OS in 11 eligible studies with high LDH level was 1.79 (95% CI = 1.47–2.12), and the pooled HR for DMFS in 9 eligible studies with high LDH level was 1.85 (95% CI = 1.48–2.22). Meanwhile, the pooled HR for DFS in 5 eligible studies with high LDH level was 1.63 (95% CI = 1.34–1.91). Egger test and funnel plots revealed that the publication bias in the current meta-analysis was insignificant. Conclusions: The present meta-analysis demonstrated that high pretreated LDH level is significantly associated with poorer OS, DMFS, and DFS, suggesting that pretreated LDH could

  9. The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01

    PubMed Central

    Creutzig, Ursula; Zimmermann, Martin; Dworzak, Michael N.; Gibson, Brenda; Tamminga, Rienk; Abrahamsson, Jonas; Ha, Shau-Yin; Hasle, Henrik; Maschan, Alexey; Bertrand, Yves; Leverger, Guy; von Neuhoff, Christine; Razzouk, Bassem; Rizzari, Carmelo; Smisek, Petr; Smith, Owen P.; Stark, Batia; Reinhardt, Dirk; Kaspers, Gertjan L.

    2014-01-01

    The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by morphology on days 15 and 28 after first reinduction in 338 patients of the international Relapsed-AML2001/01 trial. Both day 15 and day 28 status was classified as good (≤20% leukemic blasts) in 77% of patients. The correlation between day 15 and 28 blast percentages was significant, but not strong (Spearman correlation coefficient = 0.49, P<0.001). Survival probability decreased in a stepwise fashion along with rising blast counts at day 28. Patients with bone marrow blast counts at this time-point of ≤5%, 6–10%, 11–20% and >20% had 4-year probabilities of survival of 52%±3% versus 36%±10% versus 21%±9% versus 14%±4%, respectively, P<0.0001; this trend was not seen for day 15 results. Multivariate analysis showed that early treatment response at day 28 had the strongest prognostic significance, superseding even time to relapse (< or ≥12 months). In conclusion, an early response to treatment, measured on day 28, is a strong and independent prognostic factor potentially useful for treatment stratification in pediatric relapsed acute myeloid leukemia. This study was registered with ISRCTN code: 94206677. PMID:24763401

  10. Nottingham Prognostic Index Plus: Validation of a clinical decision making tool in breast cancer in an independent series.

    PubMed

    Green, Andrew R; Soria, Daniele; Stephen, Jacqueline; Powe, Desmond G; Nolan, Christopher C; Kunkler, Ian; Thomas, Jeremy; Kerr, Gillian R; Jack, Wilma; Cameron, David; Piper, Tammy; Ball, Graham R; Garibaldi, Jonathan M; Rakha, Emad A; Bartlett, John Ms; Ellis, Ian O

    2016-01-01

    The Nottingham Prognostic Index Plus (NPI+) is a clinical decision making tool in breast cancer (BC) that aims to provide improved patient outcome stratification superior to the traditional NPI. This study aimed to validate the NPI+ in an independent series of BC. Eight hundred and eighty five primary early stage BC cases from Edinburgh were semi-quantitatively assessed for 10 biomarkers [Estrogen Receptor (ER), Progesterone Receptor (PgR), cytokeratin (CK) 5/6, CK7/8, epidermal growth factor receptor (EGFR), HER2, HER3, HER4, p53, and Mucin 1] using immunohistochemistry and classified into biological classes by fuzzy logic-derived algorithms previously developed in the Nottingham series. Subsequently, NPI+ Prognostic Groups (PGs) were assigned for each class using bespoke NPI-like formulae, previously developed in each NPI+ biological class of the Nottingham series, utilising clinicopathological parameters: number of positive nodes, pathological tumour size, stage, tubule formation, nuclear pleomorphism and mitotic counts. Biological classes and PGs were compared between the Edinburgh and Nottingham series using Cramer's V and their role in patient outcome prediction using Kaplan-Meier curves and tested using Log Rank. The NPI+ biomarker panel classified the Edinburgh series into seven biological classes similar to the Nottingham series (p > 0.01). The biological classes were significantly associated with patient outcome (p < 0.001). PGs were comparable in predicting patient outcome between series in Luminal A, Basal p53 altered, HER2+/ER+ tumours (p > 0.01). The good PGs were similarly validated in Luminal B, Basal p53 normal, HER2+/ER- tumours and the poor PG in the Luminal N class (p > 0.01). Due to small patient numbers assigned to the remaining PGs, Luminal N, Luminal B, Basal p53 normal and HER2+/ER- classes could not be validated. This study demonstrates the reproducibility of NPI+ and confirmed its prognostic value in an independent cohort

  11. Prognostic significance of peroxiredoxin 1 and ezrin-radixin-moesin-binding phosphoprotein 50 in cholangiocarcinoma

    PubMed Central

    Yonglitthipagon, Ponlapat; Pairojkul, Chawalit; Chamgramol, Yaovalux; Loukas, Alex; Mulvenna, Jason; Bethony, Jeffrey; Sripa, Banchob

    2012-01-01

    Summary We performed a comparative proteomic analysis of protein expression profiles in four cholangiocarcinoma (CCA) cell lines: K100, M156, M213, and M139. The H69 biliary cell line was used as a control. Peroxiredoxin 1 (PRX1) and ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) were selected for further validation by immunohistochemistry (IHC) using a CCA tissue microarray (n=301) to assess their prognostic value in this cancer. Both PRX1 and EBP50 were overexpressed in CCA tissues compared with normal liver tissues. Of the 301 CCA cases, overexpression of PRX1 in 103 (34.3%) was associated with an age-related effect in young patients (P = 0.011) and the absence of cholangiocarcinoma in lymphatic vessels and perineural tissues (P = 0.004 and P = 0.037, respectively). Expression of EBP50 correlated with histopathologic type, being higher in 180 (59.8%) of moderately or poorly differentiated tumors (P = 0.039) and was associated with the presence of cholangiocarcinoma in lymphatic and vascular vessels (P< 0.001 and P< 0.001, respectively). The high expression of EBP50 and the low expression of PRX1 correlated with reduced survival by univariate analysis (P = 0.017 and P = 0.048, respectively). Moreover, the impact of PRX1 and EBP50 expression on patient survival was an independent predictor in multivariate analyses (P = 0.004 and P = 0.025, respectively). Therefore, altered expression of PRX1 and EBP50 may be used as prognostic markers incholangiocarcinoma. PMID:22446018

  12. Prognostic significance of circulating laminin gamma2 for early-stage non-small-cell lung cancer

    PubMed Central

    Teng, Yu; Wang, Zitong; Ma, Li; Zhang, Lina; Guo, Yinan; Gu, Meng; Wang, Ziyu; Wang, Yue; Yue, Wentao

    2016-01-01

    Background Laminin gamma2 (Ln-γ2) chain, a distinctive subunit of heterotrimeric laminin-332, is frequently upregulated in carcinomas and is of great importance in cell migration and invasion. Despite this, the status of circulating Ln-γ2 in lung cancer patients is still uncertain. Patients and methods In this retrospective study, serum samples from 538 all-stage (stages I–IV) patients with non-small-cell lung cancer (NSCLC) and 94 age-matched healthy volunteers were investigated by enzyme-linked immunosorbent assay. Data were statistically analyzed in combination with clinicopathological information. Results Circulating Ln-γ2 was markedly increased in NSCLC, even in stage I cases (P<0.01), reflecting the progression of lung cancer. Survival analysis on 370 eligible patients indicated that serum Ln-γ2-negative patients survived much longer compared with Ln-γ2-positive individuals (P=0.028), and it was especially the case for stage I (P<0.001), stage T1 (P=0.001), and stage N0 patients (P=0.038), all of whom represented early-stage cases. For the advanced patients, however, overall survivals were not significantly different among stages II–IV (P=0.830), stages T2–T4 (P=0.575), stages N1–N3 (P=0.669), and stage M1 (P=0.849). Cox analysis subsequently defined serum Ln-γ2 as an independent prognostic indicator of NSCLC, particularly for early-stage patients. Furthermore, we demonstrated the association of serum Ln-γ2 with smoking behavior, but its association with tumor progression and early prognostic significance were not altered in the nonsmoking cohort. Conclusion Our study demonstrated that elevation of circulating Ln-γ2 was an early-emerging event in NSCLC and was significantly associated with poor prognosis in NSCLC, especially for early-stage cases. PMID:27462170

  13. Prognostic and Functional Significance of MAP4K5 in Pancreatic Cancer

    PubMed Central

    Wang, Oliver H.; Azizian, Nancy; Guo, Ming; Capello, Michela; Deng, Defeng; Zang, Fenglin; Fry, Jason; Katz, Matthew H.; Fleming, Jason B.; Lee, Jeffrey E.; Wolff, Robert A.; Hanash, Samir; Wang, Huamin; Maitra, Anirban

    2016-01-01

    Objectives MAP4K5 plays an important role in regulating a range of cellular responses and is involved in Wnt signaling in hematopoietic cells. However, its functions in human malignancies have not been studied. The major objectives of this study are to examine the expression, functions and clinical significance of MAP4K5 in pancreatic ductal adenocarcinoma (PDAC). Materials and Methods The expression levels of MAP4K5, E-cadherin, vimentin, and carboxylesterase 2 (CES2) were examined by immunohistochemistry in 105 PDAC and matched non-neoplastic pancreas samples from our institution. The RNA sequencing data of 112 PDAC patients were downloaded from the TCGA data portal. Immunoblotting and RNA sequencing analysis were used to examine the expression of MAP4K5 and E-cadherin in pancreatic cancer cell lines. The effect of knockdown MAP4K5 using siRNA on the expression of CDH1 and vimentin were examined by Real-time RT-PCR in Panc-1 and AsPC-1 cells. Statistical analyses were performed using IBM SPSS Statistics. Results MAP4K5 protein is expressed at high levels specifically in the pancreatic ductal cells of 100% non-neoplastic pancreas samples, but is decreased or lost in 77.1% (81/105) of PDAC samples. MAP4K5-low correlated with the loss of E-cadherin (P = 0.001) and reduced CES2 expression (P = 0.002) in our patient populations. The expression levels of MAP4K5 mRNA directly correlated with the expression levels of CDH1 mRNA (R = 0.2490, P = 0.008) in the second cohort of 112 PDAC patients from The Cancer Genome Atlas (TCGA) RNA-seq dataset. Similar correlations between the expression of MAP4K5 and E-cadherin were observed both at protein and mRNA levels in multiple pancreatic cancer cell lines. Knockdown MAP4K5 led to decreased CDH1 mRNA expression in Panc-1 and AsPC-1 cells. MAP4K5-low correlated significantly with reduced overall survival and was an independent prognosticator in patients with stage II PDAC. Conclusions MAP4K5 expression is decreased or lost in

  14. Molecular correlates and prognostic significance of SATB1 expression in colorectal cancer

    PubMed Central

    2012-01-01

    Background Special AT-rich sequence-binding protein 1 (SATB1) is a global gene regulator that has been reported to confer malignant behavior and associate with poor prognosis in several cancer forms. SATB1 expression has been demonstrated to correlate with unfavourable tumour characteristics in rectal cancer, but its association with clinical outcome in colorectal cancer (CRC) remains unclear. In this study, we examined the prognostic impact of SATB1 expression in CRC, and its association with important molecular characteristics; i.e. beta-catenin overexpression, microsatellite instability (MSI) screening status, and SATB2 expression. Methods Immunohistochemical expression of SATB1 and beta-catenin was assessed in tissue microarrays with tumours from 529 incident CRC cases in the prospective population-based Malmö Diet and Cancer Study, previously analysed for SATB2 expression and MSI screening status. Spearmans Rho and Chi-Square tests were used to explore correlations between SATB1 expression, clinicopathological and investigative parameters. Kaplan Meier analysis and Cox proportional hazards modelling were used to explore the impact of SATB1 expression on cancer specific survival (CSS) and overall survival (OS). Results SATB1 was expressed in 222 (42%) CRC cases and negative, or sparsely expressed, in adjacent colorectal mucosa (n = 16). SATB1 expression was significantly associated with microsatellite stable tumours (p < 0.001), beta-catenin overexpression (p < 0.001) and SATB2 expression (p < 0.001). While not prognostic in the full cohort, SATB1 expression was significantly associated with poor prognosis in SATB2 negative tumours (HR = 2.63; 95% CI 1.46-4.71; pinteraction = 0.011 for CSS and HR = 2.31; 95% CI 1.32-4.04; pinteraction = 0.015 for OS), remaining significant in multivariable analysis. Conclusions The results of this study demonstrate that SATB1 expression in CRC is significantly associated with beta

  15. Prognostic significance of epithelial–mesenchymal transition-related markers in extrahepatic cholangiocarcinoma: comprehensive immunohistochemical study using a tissue microarray

    PubMed Central

    Nitta, T; Mitsuhashi, T; Hatanaka, Y; Miyamoto, M; Oba, K; Tsuchikawa, T; Suzuki, Y; Hatanaka, K C; Hirano, S; Matsuno, Y

    2014-01-01

    Background: Epithelial–mesenchymal transition (EMT) is characterised by the loss of cell-to-cell adhesion and gaining of mesenchymal phenotypes. Epithelial–mesenchymal transition is proposed to occur in various developmental processes and cancer progression. ‘Cadherin switch', a process in which cells shift to express different isoforms of the cadherin transmembrane protein and usually refers to a switch from the expression of E-cadherin to N-cadherin, is one aspect of EMT and can have a profound effect on tumour invasion/metastasis. The aim of this study was to investigate the clinicopathological significance of EMT-related proteins and cadherin switch in extrahepatic cholangiocarcinoma (EHCC). Methods: We investigated the association between altered expression of 12 EMT-related proteins and clinical outcomes in patients with EHCC (n=117) using immunohistochemistry on tissue microarrays. Results: Univariate and multivariate analyses revealed that, in addition to N classification (P=0.0420), the expression of E-cadherin (P=0.0208), N-cadherin (P=0.0038) and S100A4 (P=0.0157) was each an independent and a significant prognostic factor. We also demonstrated that cadherin switch was independently associated with poor prognosis (P=0.0143) in patients with EHCC. Conclusions: These results may provide novel information for selection of patients with EHCC who require adjuvant therapy and strict surveillance. PMID:25077440

  16. Prognostic significance of serum ERBB3 and ERBB4 mRNA in lung adenocarcinoma patients.

    PubMed

    Masroor, Mirza; Javid, Jamsheed; Mir, Rashid; Y, Prasant; A, Imtiyaz; Z, Mariyam; Mohan, Anant; Ray, P C; Saxena, Alpana

    2016-01-01

    Serum messenger RNA (mRNA) is an emerging prognostic tool for noninvasive malignant disease prognosis, and to study serum mRNA may have importance in the prognosis and detection of disease. This study aimed to evaluate the possible prognostic role of serum ERBB3 and ERBB4 mRNA expressions in lung adenocarcinoma patients. One hundred newly diagnosed lung adenocarcinoma patients and 100 age- and sex-matched healthy controls were included. Expression was analysed by quantitative real-time PCR and overall survival was analysed by Kaplan-Meier analysis. Serum ERBB3 and ERBB4 mRNA expressions was found to be significantly associated with distant metastases and TNM stages. It was observed that patients with distant metastases had 4.8- and 3.4-fold high ERBB3 and ERBB4 expression in contrast to patients without distant metastases, respectively. It was also found that ERBB3 and ERBB4 mRNA expression was 7.7-fold and 6.7-fold high in TNM stage IV compared to TNM stage I, respectively. Significantly, 2.6-fold increased serum ERBB4 mRNA expression was found in patients with pleural effusion compared to patients without pleural effusion (p = 0.005). Lung adenocarcinoma patients with ≤8- and >8-fold increased serum ERBB3 mRNA expression had 10.0 and 5.5 months of overall median survival while serum ERBB4 mRNA with ≤10- and >10-fold increased expression showed 11.4 and 5.0 months overall median survival, respectively. ERBB3 and ERBB4 together also found to be significantly associated with poor overall median survival. Patients with ≤8 + ≤10- and >8 + >10-fold expression showed 11.3 vs 4.8 months of overall median survival, respectively. In conclusion, serum ERBB3 and ERBB4 mRNA expressions may be a prognostic marker and monitoring of serum ERBB3 and ERBB4 mRNA can be one of the predictive factors for metastases and poor overall survival of lung adenocarcinoma patients. PMID:26254096

  17. Meta-Analysis of Prognostic and Clinical Significance of CD44v6 in Esophageal Cancer.

    PubMed

    Hu, Bangli; Luo, Wei; Hu, Rui-Ting; Zhou, You; Qin, Shan-Yu; Jiang, Hai-Xing

    2015-08-01

    CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis.We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects.Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR=9.19, 95% CI=6.30-13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR=6.91, 95% CI=4.81-9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56-3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P>0.05). Moreover, no publication bias was found among the studies (all P > 0.05).This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages. PMID:26252284

  18. Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma

    PubMed Central

    Ito, Takamichi; Kohashi, Kenichi; Yamada, Yuichi; Iwasaki, Takeshi; Maekawa, Akira; Kuda, Masaaki; Hoshina, Daichi; Abe, Riichiro; Furue, Masutaka; Oda, Yoshinao

    2016-01-01

    Background: The prognosis of angiosarcoma is poor and a novel treatment option for the disease is desired. The aim of this study was to investigate the prognostic significance of Forkhead box M1 (FOXM1), a transcription factor that regulates cell-cycle progression and various crucial processes in tumor progression, and its potential as a new therapeutic target. Methods: We investigated 125 angiosarcoma clinical samples (94 primary lesions and 31 metastatic lesions in 94 patients) and a human angiosarcoma cell line (HAMON) using immunohistochemical staining and molecular biological approaches. FOXM1 expression in angiosarcoma samples was also compared with that in Kaposi's sarcomas (n = 13), epithelioid hemangioendotheliomas (n = 13) and benign hemangiomas (n = 10). Results: Patients with FOXM1-overexpressing angiosarcoma had significantly shorter survival (both for disease-specific survival [DSS] and event-free survival [EFS]) than other patients (5-year DSS, 23.5% vs. 47.1%, P = 0.013; and 5-year EFS, 5.5% vs. 28.7%, P = 0.004). FOXM1 overexpression was also an independent prognostic factor for both DSS and EFS in Cox multivariate analyses (hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.10-5.81, P = 0.039; and HR 4.16, 95%CI 2.03-8.67, P = 0.0001, respectively). FOXM1 inhibition using both small interfering RNA and a specific inhibitor (thiostrepton) suppressed cell proliferation of the angiosarcoma cell line. Furthermore, FOXM1 inhibition improved the chemosensitivity to docetaxel in vitro. Conclusions: FOXM1 inhibition may be a potential therapeutic option for angiosarcoma. PMID:27162541

  19. Prognostic factors identified three risk groups in the LRF CLL4 trial, independent of treatment allocation

    PubMed Central

    Oscier, David; Wade, Rachel; Davis, Zadie; Morilla, Alison; Best, Giles; Richards, Sue; Else, Monica; Matutes, Estella; Catovsky, Daniel

    2010-01-01

    Background Many prognostic markers have been identified in chronic lymphocytic leukemia, but there have been few opportunities to assess their relative importance in a large randomized trial. The aim of this study was to determine which of the available markers independently predicted outcome in patients requiring treatment and to use these to define new risk groups. Design and Methods A broad panel of clinical and laboratory markers, measured at randomization in patients entering the LRF CLL4 trial, was assessed with respect to treatment response, progression-free and overall survival, at a median follow-up of 68 months. Results Using the factors identified as independent predictors for progression-free survival, patients were subdivided into three risk groups: 6% had poor risk with known TP53 loss of greater than 10%; 72% had an intermediate risk without TP53 loss (≤10%) and with at least one of: unmutated IGHV genes and/or IGHV3-21 usage, 11q deletion, β-2 microglobulin greater than 4 mg/L; 22% had a good risk (with none of the above and mutated IGHV genes). The 5-year progression-free survival rates for these three groups were 0%, 12% and 34%, respectively, and the corresponding 5-year overall survival rates were 9%, 53% and 79% (both P<0.00005 independent of treatment allocation). In the intermediate risk group 250 patients, with data for all three risk factors, were further subdivided into intermediate-low (one risk factor) or intermediate-high (2 or 3 risk factors). The 5-year progression-free survival rates were 18% and 7% (P=0.0001) and the 5-year overall survival rates were 68% and 40% (P<0.00005), respectively. Conclusions This study demonstrates the role of biomarkers in prognosis and shows that, in patients requiring treatment, disease stage may no longer be an independent predictor of outcome. If validated independently, the risk groups defined here may inform the design of future trials in chronic lymphocytic leukemia. (Clinicaltrials

  20. Prognostic significance of lymphocyte-to-monocyte ratio and CRP in patients with nonmetastatic clear cell renal cell carcinoma: a retrospective multicenter analysis

    PubMed Central

    Xia, Wen-Kai; Wu, Xia; Yu, Tang-Hong; Wu, Yu; Yao, Xia-Juan; Hu, Hong

    2016-01-01

    Background Inflammation has been reported to be involved in carcinogenesis and cancer progression. This study was designed to explore the prognostic significance of lymphocyte-to-monocyte ratio (LMR) and serum C-reactive protein (CRP) in nonmetastatic clear cell renal cell carcinoma (ccRCC) patients after treatment. Methods The retrospective study consisted of 985 patients with ccRCC who had undergone nephrectomy from 2005 to 2010 at multiple centers. The patients were divided into four groups using a quartile of LMR or CRP, and their associations with clinical characteristics and outcome were systematically estimated. Results Both low LMR and high CRP significantly diminished overall survival (OS) and metastasis-free survival (MFS) in patients with ccRCC. Further investigation indicated that LMR and CRP were independent prognostic factors of both OS and MFS. Integration of LMR and CRP into a predictive model, including significant variables in multivariate analysis, established a nomogram to predict accurately the 3- and 5-year survival for nonmetastatic patients with ccRCC. Conclusion LMR and CRP represent independent prognostic factors of OS and MFS for patients with ccRCC. Incorporation of LMR and CRP into the traditional TNM staging system may improve their predictive performance. PMID:27274272

  1. Prognostic significance of volume-based PET parameters in cancer patients.

    PubMed

    Moon, Seung Hwan; Hyun, Seung Hyup; Choi, Joon Young

    2013-01-01

    Accurate prediction of cancer prognosis before the start of treatment is important since these predictions often affect the choice of treatment. Prognosis is usually based on anatomical staging and other clinical factors. However, the conventional system is not sufficient to accurately and reliably determine prognosis. Metabolic parameters measured by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) have the potential to provide valuable information regarding prognosis and treatment response evaluation in cancer patients. Among these parameters, volume-based PET parameters such as metabolic tumor volume and total lesion glycolysis are especially promising. However, the measurement of these parameters is significantly affected by the imaging methodology and specific image characteristics, and a standard method for these parameters has not been established. This review introduces volume-based PET parameters as potential prognostic indicators, and highlights methodological considerations for measurement, potential implications, and prospects for further studies. PMID:23323025

  2. HK2 is a radiation resistant and independent negative prognostic factor for patients with locally advanced cervical squamous cell carcinoma

    PubMed Central

    Huang, Xinqiong; Liu, Miaomiao; Sun, Hong; Wang, Fengjun; Xie, Xiaoxue; Chen, Xiang; Su, Juan; He, Yuxiang; Dai, Youyi; Wu, Haijun; Shen, Liangfang

    2015-01-01

    The mechanism by which overexpression of hexokinase 2 (HK2) indicates locally advanced cervical squamous cell carcinoma (LACSCC) with radio-resistance is still unknown despite being an independent biomarker of poor prognosis. Here, we retrospectively analyzed 132 female patients receiving radiotherapy for cervical squamous cell carcinoma including 85 radiation-sensitive cases and 47 radiation-resistant cases. The expression of HK2 was examined by immunohistochemistry. The percentage of high HK2 expression in the radiation-resistant group differed from the radiation-sensitive group with statistical significance (P < 0.001) even if divided into three subgroups including a lower 5-year progression free survival group (PFS) for comparison (P < 0.001). The Kaplan Meier curve analysis showed that there were differences between the two groups (P < 0.001). Therefore, this study proves a close relationship between HK2 expression and radio-resistance. Multivariate Cox regression analysis implied that HK2 was an independent prognostic indicator of cervical squamous carcinoma (HR (95% CI), 2.940 (1.609, 1.609); P = 0.002). PMID:26097593

  3. Diagnostic and prognostic significance of serum soluble endoglin levels in preeclampsia and eclampsia

    PubMed Central

    Sachan, Rekha; Patel, Munna Lal; Dhiman, Soniya; Gupta, Pooja; Sachan, Pushplata; Shyam, Radhey

    2016-01-01

    Background: Preeclampsia is a multisystem disorder of unknown etiology that affects 4–5% of all pregnancies. The aim of the study was to evaluate the diagnostic accuracy of serum soluble endoglin (sEng) in preeclampsia and eclampsia and also to evaluate its prognostic significance. Materials and Methods: This prospective case–control study carried out over a period of 1 year in the Department of Obstetrics and Gynaecology, King George Medical University, Lucknow. After written informed consent and ethical clearance, total 90 subjects were enrolled. Among them, 30 subjects of eclampsia, 15 of nonsevere preeclampsia, 15 of severe preeclampsia served as cases, and 30 healthy pregnant normotensive women served as controls. Levels were estimated by enzyme-linked immunosorbent assay technique in both cases and controls. Results: Mean level was highest in eclampsia group (14.96 ± 1.96 ng/mL) and lowest in controls (2.08 ± 0.56 ng/mL). At cut-off value of sEng levels of ≥6.26 ng/mL, it was found to be 100% sensitive and 100% specific for the diagnosis of preeclampsia (area under curve =1) at 95% confidence interval. sEng levels were strongly correlated with systolic (r = 0.928) and diastolic blood pressure (r = 0.916), serum lactate dehydrogenase (r = 0.791) and serum uric acid (r = 0.722). All four maternal deaths were reported within eclampsia group, in whom the mean sEng level was significantly higher (17.84 ± 0.22) as compared to other subjects (9.50 ± 5.80). Conclusion: sEng is a novel marker for diagnosis of preeclampsia, and it can also be used as a prognostic marker to predict the severity of preeclampsia. PMID:27563629

  4. Clinical and prognostic significance of serum levels of von Willebrand factor and ADAMTS-13 antigens in AL amyloidosis.

    PubMed

    Kastritis, Efstathios; Papassotiriou, Ioannis; Terpos, Evangelos; Roussou, Maria; Gavriatopoulou, Maria; Komitopoulou, Anna; Skevaki, Chrysanthi; Eleutherakis-Papaiakovou, Evangelos; Pamboucas, Constantinos; Psimenou, Erasmia; Manios, Efstathios; Giannouli, Stavroula; Politou, Marianna; Gakiopoulou, Harikleia; Papadopoulou, Elektra; Stamatelopoulos, Kimon; Tasidou, Anna; Dimopoulos, Meletios A

    2016-07-21

    Cardiac dysfunction determines prognosis in amyloid light-chain (AL) amyloidosis. The heart is the central organ of the vascular system in which endothelium function is critical for the circulatory homeostasis, but there are limited data on endothelial function in AL amyloidosis. von Willebrand factor (VWF) has been considered as a marker of endothelial activation and dysfunction, whereas a disintegrin and metalloproteinase with thrombospondin type-1 repeats 13 (ADAMTS-13) cleaves VWF multimers, but both have been associated with prognosis in cardiovascular disease. We measured the serum levels of VWF (VWF:Ag) and ADAMTS-13 antigens in 111 newly diagnosed patients with AL amyloidosis. The levels of VWF:Ag were significantly higher than in healthy controls; 76% of patients with AL had VWF:Ag levels higher than the upper levels of controls. There was no significant association of VWF:Ag levels with patterns of organ involvement, free light-chain levels, the levels of cardiac biomarkers, or renal dysfunction but correlated with low systolic blood pressure. VWF:Ag levels ≥230.0 U/dL were associated with higher probability of early death and poor survival independently of cardiac biomarkers and low systolic blood pressure (SBP). Moreover, among patients with Mayo stage III or stage IIIB (that is stage III with N-terminal pro-brain natriuretic peptide [NTproBNP] >8500 pg/mL) disease, VWF:Ag identified subgroups of patients with very poor outcome. Low ADAMTS-13 levels correlated with high levels of NTproBNP but had no independent prognostic significance. In conclusion, high VWF:Ag levels, probably representing endothelial dysfunction, are associated with prognosis in patients with AL amyloidosis, independently of other features of the disease or cardiac biomarkers. PMID:27166361

  5. What is the Prognostic Significance of Ki-67 Positivity in Oral Squamous Cell Carcinoma?

    PubMed Central

    Xie, Shang; Liu, Ying; Qiao, Xue; Hua, Rui-Xi; Wang, Kan; Shan, Xiao-Feng; Cai, Zhi-Gang

    2016-01-01

    BACKGROUD: Numerous studies have stated that Ki-67 is a good prognostic marker in oral squamous cell carcinoma (OSCC). However, some researchers believe the contrary. To address this controversy, we performed a systematic literature retrieval to estimate the prognostic significance of Ki-67 expression in patients with OSCC. METHODS: Databases covering Pubmed, Ovid, Web of Science, Embase and the Cochrane library were searched regardless of publication year. Overall survival (OS), local recurrence (LR) and disease-free survival (DFS) were the main outcome measures. Relative risks (RRs) and its 95% confidential intervals (CIs) were used for statistical analysis. RESULTS: Twenty-seven articles with 2146 patients were included in this study. The results of the meta-analysis suggested that the pooled RRs and its CIs for OS, LR, and DFS were 1.45 (1.15 - 1.84), 1.76 (0.74 - 4.16) and 1.52 (1.07 - 2.14), respectively. However, the heterogeneities of OS and LR were obvious (I-squared (OS) = 59.4%, I-squared (LR) = 72.6%). After subgroup analysis based on systemic treatment, the cut-off value of Ki-67 expression, ethnicity and types of antibody, the heterogeneities became acceptable. It was observed that systemic treatment, cut-off values of Ki-67 expression, ethnicity and the types of antibody affected the results. The statistical analyses of subgroups suggested that non-systemic treatment, (OR=1.77, 95% CI = 1.39-2.25, p = 0.000) and Asian populations (OR=2.09, 95% CI = 1.32-3.32, p = 0.002) are high risks for Ki-67 high expression, and low cut-off value of Ki-67 expression (OR = 1.44, 95% CI = 1.001-2.072), MIB-1 antibody (OR = 1.48, OR 95% = 1.10-1.99) might affect the identification of results. CONCLUSIONS: According to this meta-analysis, high Ki-67 expression might be a negative prognostic marker of patients with OSCC, especially in Asian populations. In addition, Ki-67 expression affects the treatment response. PMID:27162533

  6. Prognostic significance of nonfatal myocardial reinfarction in survivors of a first infarction

    PubMed Central

    van Domburg, R.T.; Deckers, J.W.; van Bergen, P.F.M.M.; Azar, A.J.; Jonker, J.J.C.; Simoons, M.L.

    2001-01-01

    Background Patients who develop a reinfarction are at increased risk for subsequent reinfarctions and death. However, follow-up studies in these patients are rare. Objective The purpose of this study was to examine the risk of mortality after a first myocardial reinfarction and to determine the independent contribution of nonfatal reinfarction to the risk of subsequent mortality. Methods The prognostic value of nonfatal reinfarction was assessed in a large series (n=3097) of patients with a first myocardial infarction who participated in the ASPECT trial, comparing coumarin or matching placebo. Results A second myocardial infarction was documented in 299 patients (82% Q-wave infarctions), 45 (15%) of which were fatal. Of the 254 nonfatal reinfarctions, 31 patients (12%) died during subsequent follow-up. After adjustment for baseline characteristics, the relative risks of nonfatal reinfarction for subsequent cardiac mortality at one month were: 2.90 (1.49-5.64), at one year: 2.50 (1.47-4.23) and at three years: 2.71 (1.77-4.17). Rates of death or a second reinfarction in patients who did not undergo a revascularisation procedure after a first reinfarction were almost three times higher than in patients who did have PTCA or bypass surgery after a reinfarction (38% versus 14%; p<0.0001). Conclusion This study population with three-year follow-up confirms that nonfatal reinfarction carries a strong and independent risk for recurrent reinfarction and subsequent mortality. Thus, prevention of reinfarction by intensive treatment might contribute in reduction of mortality. PMID:25696720

  7. Prognostic significance of CD44V6 expression in osteosarcoma: a meta-analysis.

    PubMed

    Zhang, Yunyuan; Ding, Chunming; Wang, Jing; Sun, Guirong; Cao, Yongxian; Xu, Longqiang; Zhou, Lan; Chen, Xian

    2015-01-01

    Numerous individual studies evaluating the relationship between CD44V6 over-expression and prognostic impact in patients with osteosarcoma (OS) have yielded in conclusive results. This meta-analysis aimed to determine the value of cell adhesion molecule CD44V6 in prognosis of OS by conducting a systematic review and meta-analysis. A comprehensive search was conducted using PubMed (medline), Embase, ISI Web of Knowledge, Springer, the Cochrane Library, Scopus, BioMed Central, ScienceDirect, Wanfang, Weipu, and China National Knowledge Internet (CNKI) databases from inception through May 26, 2015. All available articles written in English or Chinese that investigated the expression of CD44V6 and the prognosis of OS were included. The quantity of the studies was evaluated according to the critical review checklist of the Dutch Cochrane Centre proposed by MOOSE. Finally, a total of eight studies with 486 OS patients were involved and the results indicated that the positive expression of CD44V6 predicts neoplasm metastasis (RR = 1.76, 95 % CI 1.38-2.25, p < 0.00001), and poor survival in OS with the pooled HR of 1.53 (95 % CI 1.25-1.88, p < 0.0001). No significant heterogeneity was observed among all studies. In conclusion, the present meta-analysis and systematic review strongly suggest that CD44V6 over-expression is associated with overall survival rate and metastasis in OS, and may be used as a prognostic biomarker to guide the clinical therapy for OS. PMID:26697855

  8. Prognostic significance of miR-126 in various cancers: a meta-analysis

    PubMed Central

    Dong, Yuanli; Fu, Chengrui; Guan, Hui; Zhang, Zicheng; Zhou, Tao; Li, Baosheng

    2016-01-01

    Objective Recent studies have demonstrated that microRNA-126 (miR-126) might be a promising prognostic factor for cancer patients. This meta-analysis was conducted to assess the effectiveness of miR-126 as a prognostic biomarker for various cancers. Methods The search of studies was performed by using PubMed and Embase until January 22, 2016. Pooled hazard ratio (HR) with 95% confidence interval (CI) for patients’ survival was calculated. A fixed-effect or random-effects model was applied according to heterogeneity. The trim and fill method was used to adjust pooled HR. Results In all 17 articles comprising of 2,437 participants were included in this meta-analysis. The results indicated that a high level of miR-126 played a favorable role in the overall survival (HR 0.70, 95% CI: 0.62–0.79, random-effects model), with a heterogeneity measure index of I2=63.2% (P<0.01). Subgroup analyses showed that pooled HR was more significant in patients with digestive system cancers (HR 0.70, 95% CI: 0.59–0.83, fixed-effects model) and respiratory system cancers (HR 0.71, 95% CI: 0.59–0.85, random-effects model). Owing to publication bias, HR was adjusted to 0.59 (0.463–0.752, P<0.01) by the trim and fill method. Conclusion miR-126 could be a promising biomarker for cancer prognosis prediction, especially in patients with digestive or respiratory system cancers. PMID:27217773

  9. Analysis of the invasive edge in primary and secondary oral squamous cell carcinoma: An independent prognostic marker: A retrospective study

    PubMed Central

    Nadaf, Afreen; Bavle, Radhika M; Soumya, M; D'mello, Sarah; Kuriakose, Moni Abraham; Govindan, Sindhu

    2016-01-01

    (43.5%) of inflammation was predominant and very mild grade (5.4%) was the least. All the parameters showed a statistically significant difference on the application of Fisher's exact test between the two groups. Conclusion: Our study showed that POI could serve as an individual prognostic marker irrespective of the histologic differentiation of tumor. Tumor desmoplasia could be considered as an important reflection of the tumor-host interaction, especially in aggressive cancers. Host immune defense, especially tumor infiltrating lymphocytes must be noted as critical factors related to survival rate in OSCC patients. Assessment of mentioned parameters may lead to sound prognostic assessment and appropriate treatment planning thus reducing the possibility of recurrence or relapse. Hence, the parameters evaluated in our study could serve as independent or interdependent prognostic markers. PMID:27601816

  10. The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ERα, and is an independent prognostic factor in node-negative breast cancer.

    PubMed

    Brennan, D J; O'Connor, D P; Laursen, H; McGee, S F; McCarthy, S; Zagozdzon, R; Rexhepaj, E; Culhane, A C; Martin, F M; Duffy, M J; Landberg, G; Ryden, L; Hewitt, S M; Kuhar, M J; Bernards, R; Millikan, R C; Crown, J P; Jirström, K; Gallagher, W M

    2012-07-26

    Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n=690; P=0.002, 0.013). We also show that CART increases the transcriptional activity of ERα in a ligand-independent manner via the mitogen-activated protein kinase pathway and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. Additionally, we demonstrate that CART expression in ER-positive breast cancer cell lines protects against tamoxifen-mediated cell death and that high CART expression predicts disease outcome in tamoxifen-treated patients in vivo in three independent breast cancer cohorts. We believe that CART profiling will help facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow for the personalization of therapy. PMID:22139072

  11. Clinical Significance of the Prognostic Nutritional Index for Predicting Short- and Long-Term Surgical Outcomes After Gastrectomy: A Retrospective Analysis of 7781 Gastric Cancer Patients.

    PubMed

    Lee, Jee Youn; Kim, Hyoung-Il; Kim, You-Na; Hong, Jung Hwa; Alshomimi, Saeed; An, Ji Yeong; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong-Bai

    2016-05-01

    To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy.Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer.We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups.Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212-1.869, P <0.001), old age, male sex, high body mass index, medical comorbidity, total gastrectomy, and combined resection to be independent predictors of postoperative complications. Among these, only low PNI (OR = 4.279, 95% CI = 1.760-10.404, P = 0.001) and medical comorbidity were independent predictors of postoperative mortality. For long-term outcomes, low PNI was a poor prognostic factor for overall survival, but not recurrence (overall survival: hazard ratio [HR] = 1.383, 95% CI = 1.221-1.568, P < 0.001; recurrence-free survival: HR = 1.142, 95% CI = 0.985-1.325, P = 0.078).PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. Although PNI was an independent prognostic factor for overall survival, the index was not associated with cancer recurrence. PMID:27149460

  12. Prognostic significance of TAZ expression in various cancers: a meta-analysis

    PubMed Central

    Feng, Juntao; Ren, Pengwei; Gou, Jinhai; Li, Zhengyu

    2016-01-01

    Background The overexpression of transcriptional coactivator with PDZ-binding motif (TAZ), a Hippo pathway effector, was detected in a variety of cancers. However, controversies remain in published studies on the prognostic value of TAZ expression in cancer. We performed a meta-analysis to demonstrate the prognostic significance of TAZ in overall survival (OS) and its association with clinicopathologic characteristics. Methods A systematic literature search was performed by using PubMed, EMBASE, and Web of Science databases for eligible studies investigating the association between TAZ and survival. After extracting data, we used hazard ratio (HR), odds ratio (OR) and 95% confidence intervals (95% CIs) for association evaluation, I2 for heterogeneity across studies, and Egger’s test and Begg’s funnel plot for publication bias assessment. Results A total of 15 studies including 2,881 patients were analyzed. Pooled results showed that a high TAZ was significantly associated with poor OS (HR =1.82, 95% CI =1.58–2.11; I2=33%; P=0.11). Subgroup analysis indicated significant correlation between TAZ overexpression and OS in patients stratified by ethnicity, sample size, sample source, and staining location. Furthermore, TAZ overexpression was associated with worse OS in hepatocellular carcinoma (HR =2.26, 95% CI =1.43–3.57; P=0.49) and gastrointestinal cancers (HR =2.00, 95% CI =1.54–2.58; P=0.97), but not in non-small-cell lung cancer (HR =1.71, 95% CI =0.93–3.14; P=0.08). TAZ overexpression was also found to be significantly associated with some clinicopathologic characteristics, including TNM stage (OR =2.56, 95% CI =1.60–4.11; P=0.52), tumor differentiation (OR =3.08, 95% CI =1.25–7.63; P=0.01), and lymph node metastasis (OR =2.53, 95% CI =1.81–3.53; P=0.58). Conclusion TAZ overexpression is not only a predictive factor of poor prognosis but also associated with advanced TNM stage, poor tumor differentiation, and lymph node metastasis. PMID:27601916

  13. Prognostic Significance of HER-2 Status in Women With Inflammatory Breast Cancer

    PubMed Central

    Dawood, Shaheenah; Broglio, Kristine; Gong, Yun; Yang, Wei-Tse; Cristofanilli, Massimo; Kau, Shu-Wan; Meric-Bernstam, Funda; Buchholz, Thomas A.; Hortobagyi, Gabriel N; Gonzalez-Angulo, Ana M.

    2015-01-01

    BACKGROUND Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer with poorly understood prognostic variables. The purpose of this study was to define the prognostic impact of HER-2 status on survival outcomes of patients with IBC. METHODS In all, 179 patients with IBC, diagnosed between 1989 and 2005, with known HER-2 status, and treated with an anthracycline-based chemotherapy regimen without trastuzumab, were included in the analysis. Patients with HER-2-positive disease who received trastuzumab at the time of disease recurrence were included. Survival outcomes were estimated by the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. A Cox proportional hazards model was fitted to determine the association of survival outcomes with HER-2 status after adjusting for patient and tumor characteristics. RESULTS A total of 111 patients (62%) had HER-2-negative disease and 68 (38%) had HER-2-positive disease. The median follow-up among all patients was 35 months. At the time of the analysis, 62 patients (55.9%) with HER-2-negative disease and 42 patients (61.8%) with HER-2-positive disease had a recurrence. Thirty-one patients (73.8%) with HER-2-positive disease who had a disease recurrence went on to receive trastuzumab. On univariate analysis, no statistically significant difference was observed for either recurrence-free survival (P = .75) or overall survival (P = .24) between patients who had HER-2-positive disease and those who had HER-2-negative disease. In a multivariate model, HER-2 status did not appear to significantly affect recurrence-free survival (hazards ratio [HR] of 0.75; 95% confidence interval [95% CI], 0.46–1.22 [P = .241]). In the multivariate model, patients with HER-2-positive disease had a decreased hazard of death (HR of 0.56; 95% CI, 0.34–0.93 [P = .024]) compared with patients with HER-2-negative disease. CONCLUSIONS HER-2 status, in the absence of trastuzumab, did not appear to

  14. Prognostic Factors Affecting Locally Recurrent Rectal Cancer and Clinical Significance of Hemoglobin

    SciTech Connect

    Rades, Dirk Kuhn, Hildegard; Schultze, Juergen; Homann, Nils; Brandenburg, Bernd; Schulte, Rainer; Krull, Andreas; Schild, Steven E.; Dunst, Juergen

    2008-03-15

    Purpose: To investigate potential prognostic factors, including hemoglobin levels before and during radiotherapy, for associations with survival and local control in patients with unirradiated locally recurrent rectal cancer. Patients and Methods: Ten potential prognostic factors were investigated in 94 patients receiving radiotherapy for recurrent rectal cancer: age ({<=}68 vs. {>=}69 years), gender, Eastern Cooperative Oncology Group performance status (0-1 vs. 2-3), American Joint Committee on Cancer (AJCC) stage ({<=}II vs. III vs. IV), grading (G1-2 vs. G3), surgery, administration of chemotherapy, radiation dose (equivalent dose in 2-Gy fractions: {<=}50 vs. >50 Gy), and hemoglobin levels before (<12 vs. {>=}12 g/dL) and during (majority of levels: <12 vs. {>=}12 g/dL) radiotherapy. Multivariate analyses were performed, including hemoglobin levels, either before or during radiotherapy (not both) because these are confounding variables. Results: Improved survival was associated with better performance status (p < 0.001), lower AJCC stage (p = 0.023), surgery (p = 0.011), chemotherapy (p = 0.003), and hemoglobin levels {>=}12 g/dL both before (p = 0.031) and during (p < 0.001) radiotherapy. On multivariate analyses, performance status, AJCC stage, and hemoglobin levels during radiotherapy maintained significance. Improved local control was associated with better performance status (p = 0.040), lower AJCC stage (p = 0.010), lower grading (p = 0.012), surgery (p < 0.001), chemotherapy (p < 0.001), and hemoglobin levels {>=}12 g/dL before (p < 0.001) and during (p < 0.001) radiotherapy. On multivariate analyses, chemotherapy, grading, and hemoglobin levels before and during radiotherapy remained significant. Subgroup analyses of the patients having surgery demonstrated the extent of resection to be significantly associated with local control (p = 0.011) but not with survival (p = 0.45). Conclusion: Predictors for outcome in patients who received radiotherapy for

  15. Prognostic significance of Minichromosome maintenance protein 7 and Geminin expression in patients with 109 soft tissue sarcomas

    PubMed Central

    HAMAMOTO, YUKI; SHOMORI, KOHEI; NOSAKA, KANAE; HARUKI, TOMOHIRO; TESHIMA, RYOTA; ITO, HISAO

    2010-01-01

    Minichromosome maintenance complex (MCM2-7) and Geminin are important in the prevention of DNA re-replication in the cell cycle, and are also prognostic markers for numerous human malignancies. The present study examined Minichromosome maintenance protein 7 (MCM7) and Geminin expression in human soft tissue sarcomas (STSs) to clarify their correlation to the clinicopathological factors. Immunohistochemistry was performed to detect the expression of MCM7, Geminin and Ki-67 on paraffin-embedded sections of 109 STSs. Labeling indices (LIs) of the molecules were evaluated in the tumors. Higher LIs of MCM7, Geminin and Ki-67 were significantly correlated with distant metastasis (P<0.01), histological grade (P<0.01) and poor prognosis (P<0.01), respectively. LIs of MCM7 and Geminin were significantly correlated with Ki-67 LIs, (MCM7/Ki-67: rs=0.745, P<0.01 and Geminin/Ki-67: rs=0.604, P<0.01). Multivariate analyses showed that the higher LIs of Geminin, but not MCM7 and Ki-67, were shown to be an independent factor of poorer prognosis (relative risk 2.72, P=0.013). The immunohistochemical expression of MCM7 and Geminin may be novel and useful markers for evaluating the prognosis in patients with human STS. PMID:22966367

  16. Interleukin 6 Receptor Is an Independent Prognostic Factor and a Potential Therapeutic Target of Ovarian Cancer

    PubMed Central

    Isobe, Aki; Sawada, Kenjiro; Kinose, Yasuto; Ohyagi-Hara, Chifumi; Nakatsuka, Erika; Makino, Hiroshi; Ogura, Tomonori; Mizuno, Tomoko; Suzuki, Noriko; Morii, Eiichi; Nakamura, Koji; Sawada, Ikuko; Toda, Aska; Hashimoto, Kae; Mabuchi, Seiji; Ohta, Tsuyoshi; Morishige, Ken-ichirou; Kurachi, Hirohisa; Kimura, Tadashi

    2015-01-01

    Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical outcomes of patients, and found that a high-level of IL-6R expression but not IL-6 expression in cancer cells is an independent prognostic factor. In in vitro analyses using ovarian cell lines, while six (RMUG-S, RMG-1, OVISE, A2780, SKOV3ip1 and OVCAR-3) of seven overexpressed IL-6R compared with a primary normal ovarian surface epithelium, only two (RMG-1, OVISE) of seven cell lines overexpressed IL-6, suggesting that IL-6/IL-6R signaling exerts in a paracrine manner in certain types of ovarian cancer cells. Ovarian cancer ascites were collected from patients, and we found that primary CD11b+CD14+ cells, which were predominantly M2-polarized macrophages, are the major source of IL-6 production in an ovarian cancer microenvironment. When CD11b+CD14+ cells were co-cultured with cancer cells, both the invasion and the proliferation of cancer cells were robustly promoted and these promotions were almost completely inhibited by pretreatment with anti-IL-6R antibody (tocilizumab). The data presented herein suggest a rationale for anti-IL-6/IL-6R therapy to suppress the peritoneal spread of ovarian cancer, and represent evidence of the therapeutic potential of anti-IL-6R therapy for ovarian cancer treatment. PMID:25658637

  17. Prognostic significance of circulating tumor cells in esophageal carcinoma: a meta-analysis

    PubMed Central

    Qiao, Guang-Lei; Qi, Wei-Xiang; Jiang, Wei-Hua; Chen, Ying; Ma, Li-Jun

    2016-01-01

    Purpose The prognostic significance of circulating tumor cells (CTCs) in esophageal carcinoma (EC) is controversial. We aim to assess its association with clinicopathological and prognostic relevance in EC by using a meta-analysis. Methods We searched PubMed, Cochrane Database, Embase databases, and the references in relevant studies that assessed the clinicopathological or prognostic relevance of CTCs in peripheral blood of patients with EC. Statistical analyses were conducted by using Stata software to calculate the pooled odds ratio (OR), hazard ratio (HR), and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies. The subgroup analyses were performed according to ethnicity, histological type, and detection method. Results Sixteen trials containing 1,260 patients were included for analysis. Pooled results showed that presence of CTCs was significantly associated with poor overall survival (HR =1.71, 95% CI [1.30, 2.12], P<0.001) and progression-free survival (HR =1.67, 95% CI [1.19, 2.15], P<0.001) in EC patients. Subgroup analysis indicated that presence of CTCs was closely associated with worse overall survival (Asian: HR =1.66, 95% CI [1.24, 2.08], P<0.001; squamous cell carcinoma [SCC]: HR =1.66, 95% CI [1.24, 2.08], P<0.001; no polymerase chain reaction [PCR]: HR =2.08, 95% CI [1.40, 2.76], P<0.001) and progression-free survival (Asian: HR =1.63, 95% CI [1.15, 2.12], P<0.001; SCC: HR =1.63, 95% CI [1.15, 2.12], P<0.001; PCR: HR =1.63, 95% CI [1.15, 2.12], P<0.001). Additionally, ORs showed that presence of CTCs was significantly correlated with tumor node metastasis (TNM) staging (overall: OR = 1.96, 95% CI [1.34, 2.87], P=0.001; Asian: OR =2.09, 95% CI [1.37, 3.19], P=0.001; SCC: OR =1.97, 95% CI [1.21, 3.07], P=0.003; PCR: OR =2.23, 95% CI [1.43, 3.47], P<0.001), venous invasion (overall: OR =2.23, 95% CI [1.46, 3.40], P<0.001; Asian: OR =2.23, 95% CI [1.46, 3.40], P<0.001; SCC: OR =2.23, 95

  18. Clinical and prognostic significance of HIF-1α in glioma patients: a meta-analysis

    PubMed Central

    Liu, Qi; Cao, Peicheng

    2015-01-01

    Gliomas are the most common brain tumors, leading to significant cancer-related mortality worldwide. Hypoxia-inducible factor 1-alpha (HIF-1α) was shown to be involved in the pathophysiology and management of glioma, and might offer a therapeutic target. However, the results remain inconclusive. The purpose of this study was to systematically investigate the clinical and prognostic significance of HIF-1α expression in patients with glioma. Relevant studies published between 2000 and 2015 were searched in the electronic databases. The odds ratio (OR), risk ratio (RR) and mean difference (MD) with their 95% confidence intervals (CI) were employed to calculate the strength of significance. Finally, a total of 24 articles were retrieved, including 1422 glioma patients. No significant heterogeneity was presented between studies (I2<50%, P>0.01). Overall, our results showed that HIF-1α expression was significantly associated with high WHO grade (III+IV) of glioma (OR=8.59, 95% CI=6.56-11.24, P<0.00001). This significant relationship was also found between HIF-1α expression and microvascular density (MD=26.32, 95% CI=14.48-38.16, P<0.0001), overall survival (OS) (3-year OS: RR=0.48, 95% CI=0.35-0.66, P<0.00001; 2-year OS: RR=0.53, 95% CI=0.38-0.73, P<0.0001; 1-year OS: RR=0.79, 95% CI=0.66-0.95, P=0.01), and the cumulative survival time. However, HIF-1α expression was not associated with age and gender of glioma patients (P>0.05). In conclusions, our results suggested that HIF-1α expression was associated with high grade of glioma and OS, indicating that HIF-1α could predict prognosis and provide clinical insights into the therapeutic strategy for patients with glioma. More studies concerning other populations are also needed in the future research. PMID:26885182

  19. Prognostic Significance of Molecular Analysis of Peritoneal Fluid for Patients with Gastric Cancer: A Meta-Analysis

    PubMed Central

    Chen, Mo; Wu, Junchao; Hu, Renwei; Tang, Chengwei

    2016-01-01

    Background Accurately distinguishing serosal invasion in patients with gastric cancer (GC) prior to surgery can be difficult. Molecular analysis of peritoneal fluid (MAPF) for free cancer cells with higher sensitivity than other methods; however, its prognostic value for GC remains controversial, precluding its application in clinical practice. Methods PubMed, EMBASE and other databases were systematically searched. Thirty-one studies were eligible for the meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled for overall survival (OS), disease-free survival (DFS) and peritoneal recurrence-free survival (PRF). Results The current meta-analysis focused on patients with GC and negative cytological diagnoses. The results showed that positive MAPF status (MAPF+) led to poorer prognoses for OS (HR 2.59, 95% CI 1.99–3.37), DFS (HR 4.92, 95% CI 3.28–7.37) and PRF (HR 2.81, 95% CI 2.12–3.72) compared with negative MAPF status (MAPF-). Moreover, among the patients with GC who received curative treatment, the MAPF+ patients had poorer prognoses for OS (HR 3.27, 95% CI 2.49–4.29), DFS (HR 3.90, 95% CI 2.74–5.57) and PRF (HR 5.45, 95% CI 3.70–8.03). A meta-analysis of multivariate-adjusted HRs demonstrated that MAPF+ status was an independent prognostic factor for patients with GC who underwent curative treatment (OS: HR 2.19, 95% CI 1.47–3.28; PRF: HR 3.44, 95% CI 2.01–5.87). Using the identical target genes (CEA, CEA/CK20) as molecular markers, the patients with GC who were MAPF+ had significantly worse prognoses for OS (CEA: HR 3.03, 95% CI 2.29–4.01; CEA/CK20: HR 4.24, 95% CI 2.42–7.40), DFS (CEA: HR 3.99, 95% CI 2.24–7.12; CEA/CK20: HR 4.31, 95% CI 1.49–2.48) and PRF (CEA: HR 4.45, 95% CI 2.72–7.31; CEA/CK20: HR 6.46, 95% CI 3.62–11.55) than the patients who were MAPF-. Conclusion/Significance The above results demonstrate that MAPF could be a prognostic indicator for patients with GC who have a negative cytological

  20. Prognostic significance of CD169-positive lymph node sinus macrophages in patients with endometrial carcinoma.

    PubMed

    Ohnishi, Koji; Yamaguchi, Munekage; Erdenebaatar, Chimeddulam; Saito, Fumitaka; Tashiro, Hironori; Katabuchi, Hidetaka; Takeya, Motohiro; Komohara, Yoshihiro

    2016-06-01

    Lymph node (LN) macrophages play critical roles in anti-tumor immunity, which develops via the activation of cytotoxic T cells (CTL) and NK cells. The present study aims to determine the prognostic significance of CD169(+) LN macrophages in patients with endometrial carcinoma (EC). The number of CD169(+) cells or the CD169(+) -to-CD68(+) macrophage ratio in regional LN (RLN), and the number of CD8(+) CTL or CD57(+) NK cells in tumor tissues were investigated by immunohistochemistry in paraffin-embedded tissue samples from 79 patients with EC. A high density of CD169(+) cells in the RLN of patients with EC was correlated with an early clinical stage or no LN metastasis. A high number of CD169(+) cells and a high CD169(+) -to-CD68(+) macrophage ratio were significantly associated with longer overall survival in EC. We also found that the density of CD169(+) macrophages was positively correlated with the number of CD8(+) CTL and CD57(+) NK cells that infiltrated into tumor tissues. A high density of CD57(+) cells in EC tissues was associated with a better prognosis, while a high density of CD8(+) cells was not linked to an altered prognosis. The present study showed that the density of CD169(+) macrophages in RLN was associated with an improved prognosis in EC patients. CD169(+) macrophages in RLN might represent a useful marker for assessing clinical prognoses and monitoring anti-tumor immunity in patients with EC. PMID:26991548

  1. Expression and Prognostic Significance of p53 in Glioma Patients: A Meta-analysis.

    PubMed

    Jin, Yueling; Xiao, Weizhong; Song, Tingting; Feng, Guangjia; Dai, Zhensheng

    2016-07-01

    Glioma is a brain tumor deriving from the neoplastic glial cells or neuroglia. Due to its resistance to anticancer drugs and different disease progress of individuals, patients with high-grade glioma are difficult to completely cure, leading to a poor prognosis and low overall survival. Therefore, there is an urgent need to look for prognostic and diagnostic indicators that can predict glioma grades. P53 is one of the widely studied biomarkers in human glioma. The purpose of this study was to comprehensively evaluate the significance of p53 expression in glioma grades and overall survival. We searched commonly used electronic databases to retrieve related articles of p53 expression in glioma. Overall, a total of 21 studies including 1322 glioma patients were finally screened out. We observed that the frequency of p53 immuno-positivity was higher in high-grade patients than that in low-grade category (63.8 vs. 41.6 %), and our statistic analysis indicated that p53 expression was associated with pathological grade of glioma (OR 2.93, 95 % CI 1.87-4.60, P < 0.00001). This significant correction was also found in 1-, 3- and 5-year overall survival. However, no positive relationship was found between age, sex, tumor size and p53 expression in patients with glioma. In conclusion, our results suggested that p53 immunohistochemical expression might have an effective usefulness in predicting the prognosis in patients with glioma. PMID:27038932

  2. Incidence and prognostic significance of atrial fibrillation in acute myocardial infarction: the GISSI-3 data

    PubMed Central

    Pizzetti, F; Turazza, F; Franzosi, M; Barlera, S; Ledda, A; Maggioni, A; Santoro, L; Tognoni, G

    2001-01-01

    BACKGROUND—Atrial fibrillation is the most common supraventricular arrhythmia in patients with acute myocardial infarction. Recent advances in pharmacological treatment of myocardial infarction may have changed the impact of this arrhythmia.
OBJECTIVE—To assess the incidence and prognosis of atrial fibrillation complicating myocardial infarction in a large population of patients receiving optimal treatment, including angiotensin converting enzyme (ACE) inhibitors.
METHODS—Data were derived from the GISSI-3 trial, which included 17 944 patients within the first 24 hours after acute myocardial infarction. Atrial fibrillation was recorded during the hospital stay, and follow up visits were planned at six weeks and six months. Survival of the patients at four years was assessed through census offices.
RESULTS—The incidence of in-hospital atrial fibrillation or flutter was 7.8%. Atrial fibrillation was associated with indicators of a worse prognosis (age > 70 years, female sex, higher Killip class, previous myocardial infarction, treated hypertension, high systolic blood pressure at entry, insulin dependent diabetes, signs or symptoms of heart failure) and with some adverse clinical events (reinfarction, sustained ventricular tachycardia, ventricular fibrillation). After adjustment for other prognostic factors, atrial fibrillation remained an independent predictor of increased in-hospital mortality: 12.6% v 5%, adjusted relative risk (RR) 1.98, 95% confidence interval (CI) 1.67 to 2.34. Data on long term mortality (four years after acute myocardial infarction) confirmed the persistent negative influence of atrial fibrillation (RR 1.78, 95% CI 1.60 to 1.99).
CONCLUSIONS—Atrial fibrillation is an indicator of worse prognosis after acute myocardial infarction, both in the short term and in the long term, even in an unselected population.


Keywords: atrial fibrillation; acute myocardial infarction; prognosis PMID:11602545

  3. Expression analysis and prognostic significance of the SRA1 gene, in ovarian cancer

    SciTech Connect

    Leoutsakou, Theoni; Talieri, Maroulio; Scorilas, Andreas . E-mail: ascorilas@biol.uoa.gr

    2006-06-02

    The SR-related-CTD-associated-factors (SCAFs) have the ability to interact with the C-terminal domain of the RNA polymerase II, linking this way transcription to splicing. SRA1 (SR-A1) gene, encoding for a human high-molecular weight SCAF protein, is located on chromosome 19, between the IRF3 and the R-RAS oncogene and it has been demonstrated from members of our group that SRA1 is constitutively expressed in most of the human tissues, while it is overexpressed in a subset of ovarian tumors. In this study, we examine the expression of SRA1 gene in 111 ovarian malignant tissues and in the human ovarian carcinoma cell lines OVCAR-3, TOV21-G, and ES-2, using a semi-quantitative RT-PCR method. SRA1 gene was overexpressed in 61/111 (55%) of ovarian carcinomas. This higher expression was positively associated to the size of the tumor (p < 0.001), the grade and the stage of the disease (p = 0.003 and p = 0.006, respectively), and the debulking success (p < 0.001). Kaplan-Meier survival analysis revealed that lower SRA1 expression increases the probability of both the longer overall and the progression free survival of the patients. Multivariate Cox regression analysis revealed that SRA1 may be used as an independent prognostic biomarker in ovarian cancer. Our results suggest that SRA1 is associated with cancer progression and may possibly be characterized as a new marker of unfavorable prognosis for ovarian cancer.

  4. MicroRNA-335 represents an independent prognostic marker in cervical cancer.

    PubMed

    Wang, Changhe; Jiang, Tao

    2015-08-01

    Advanced stages with distant metastases or recurrence lack reliable prognostic predictor for cervical cancer. Therefore, the purpose of this study was to investigate the clinical significance of miR-335 expression in cervical cancer. A total of 138 cervical cancer samples were collected, and normal cervical tissues were obtained as matched-pair controls. The level of miR-335 expression was examined using quantitative real-time polymerase chain reaction. Overall survival was analyzed using Kaplan-Meier method. Moreover, the relationship between the expression of miR-335 and the clinicopathological features was further analyzed using Cox regression. Lower miR-335 expression was found in cervical cancer specimens. Cervical cancer patients with reduced miR-335 level had shorter survival time, compared with those with high levels of miR-335 expression (P = 0.011, log-rank = 6.458). Through Cox regression, we found that miR-335 expression was associated with the survival of cervical cancer (RR = 0.251, 95 % CI 0.095-0.663, P = 0.005). The results suggested that miR-335 expression was decreased in cervical cancer specimens and lower miR-335 expression resulted in poorer survival in patients with cervical cancer. Our findings indicated that miR-335 may be a candidate factor for predicting prognosis for cervical cancer. PMID:25712373

  5. Prognostic significance of interleukin-6 single nucleotide polymorphism genotypes in neuroblastoma: rs1800795 (promoter) and rs8192284 (receptor)

    PubMed Central

    Lagmay, Joanne P.; London, Wendy B.; Gross, Thomas G.; Termuhlen, Amanda; Sullivan, Nicholas; Axel, Amy; Mundy, Bethany; Ranalli, Mark; Canner, Jason; McGrady, Patrick; Hall, Brett

    2009-01-01

    Purpose Neuroblastoma is a childhood cancer of the sympathetic nervous system and many patients present with high risk disease. Risk stratification, based on pathology and tumor-derived biomarkers, has improved prediction of clinical outcomes, but overall survival rates remain unfavorable and new therapeutic targets are needed. Some studies suggest a link between interleukin-6 and more aggressive behavior in neuroblastoma tumor cells. Therefore, we examined the impact of two IL-6 single nucleotide polymorphisms (SNP) on neuroblastoma disease progression. Experimental design DNA samples from 96 high risk neuroblastoma patients were screened for two SNP that are known to regulate the serum levels of IL-6 and the soluble IL-6 receptor (IL-6R), rs1800795 and rs8192284 respectively. The genotype for each SNP was determined in a blinded fashion and independent statistical analysis was performed to determine SNP-related event free survival (EFS) and overall survival (OS) rates. Results The rs1800795 IL-6 promoter SNP is an independent prognostic factor for EFS and OS in -high risk neuroblastoma patients. In contrast, the rs8192284 IL-6 receptor SNP revealed no prognostic value. Conclusions The rs1800795 SNP (-174 IL-6 (G>C) represents a novel and independent prognostic marker for both EFS and OS in high risk neuroblastoma. Since the rs1800795 SNP (-174 IL-6 (G>C) has been shown to correlate with production of IL-6, this cytokine may represent a target for development of new therapies in neuroblastoma. PMID:19671870

  6. Overexpression of Transient Receptor Protein Cation Channel Subfamily A Member 1, Confers an Independent Prognostic Indicator in Nasopharyngeal Carcinoma

    PubMed Central

    Wu, You-Ting; Yen, Shao-Lun; Li, Chien-Feng; Chan, Ti-Chun; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Shiue, Yow-Ling

    2016-01-01

    Background: Detection of oncogenes provides chances to understand tumor development and progression. Transient receptor protein cation channel subfamily A, member 1 (TRPA1) transcript was significantly upregulated in nasopharyngeal carcinoma (NPC) with a stepwise upregulation from low- to high-stage NPCs from a preliminary data analysis in the Gene Expression Omnibus database. The TRPA1 gene is a member of the TRP channel family, encoding integral membrane proteins that functions as cation channels. Loss of calcium homeostasis takes place in cancer cells. Methods: Immunostaining of TRPA1 was analyzed on 124 biopsies from NPC patients retrospectively. The H-score method was used to evaluate the immunoexpression of TRPA1. The correlations between H-score of TRPA1 protein level and clinicopathological factors, as well as the significances of TRPA1 protein level for disease-specific, distal-metastasis-free and local recurrence-free survivals were assessed. Results: These patients were characterized to be no initial metastasis and medicated with the traditional procedure. The TRPA1 score was found to be associated with clinicopathological parameters and patient survivals. Along with the guideline of 7th edition of the American Joint Committee on Cancer, we found that TRPA1 upregulation (50%) was associated with advanced primary tumor (P = 0.009) and overall clinical stage (P = 0.019). In univariate log-rank testing, primary tumor, nodal status, stage and TRPA1 protein level significantly contributed to worse disease-specific survival, distal metastasis-free survival and local recurrence-free survival. In multivariate analysis, high TRPA1 protein level and tumor stage emerged as independent prognostic indicators for inferior disease-specific survival (P = 0.014; P = 0.003), distal metastasis-free survival (P = 0.004; P = 0.034) and recurrence-free survival (P = 0.017; P = 0.015). Conclusions: The upregulation of TRPA1 protein level is frequently correlated to unfavorable

  7. Integrin α5 promotes tumor progression and is an independent unfavorable prognostic factor in esophageal squamous cell carcinoma.

    PubMed

    Xie, Jian-Jun; Guo, Jin-Cheng; Wu, Zhi-Yong; Xu, Xiu-E; Wu, Jian-Yi; Chen, Bo; Ran, Li-Qiang; Liao, Lian-Di; Li, En-Min; Xu, Li-Yan

    2016-02-01

    The integrin family plays a major role in complex biological events such as differentiation, development, wound healing, and the altered adhesive and invasive properties of tumor cells. The expression and function of integrin α5 in esophageal squamous cell carcinoma (ESCC) are not clear. Here, by using tissue microarrays and immunohistochemical method, integrin α5 expression was retrospectively evaluated in 147 samples of human ESCC. Results showed that expression of integrin α5 was heterogeneous and varied from negative to intense expression in a membrane and cytoplasmic distribution manner. High expression of integrin α5 was significantly correlated with lymph node metastasis (P = .042) and tumor size (P = .042). Kaplan-Meier analysis revealed that high expression of integrin α5 was related to poor overall survival of ESCC patients (P = .018). Multivariate analysis suggested that integrin α5 expression status was an independent prognostic factor for ESCC (P = .003). Moreover, integrin α5 expression was associated with the survival of patients with lymph node metastasis (P = .020), but did not influence the survival of patients without lymph node metastasis. Finally, we found that RNAi-mediated knockdown of integrin α5 led to decreased growth, migration, and invasion of ESCC cells. Combined, integrin α5 might play important roles in the progression of ESCC. Integrin α5 is a novel biomarker to predict the prognosis of ESCC patients. PMID:26772401

  8. Immunohistochemical Expression and Prognostic Significance of CD97 and its Ligand DAF in Human Cervical Squamous Cell Carcinoma.

    PubMed

    He, Ying; Wang, Wei; Xu, Lian; Li, Li; Liu, Juan; Feng, Min; Bu, Hong

    2015-09-01

    Accumulating evidences had demonstrated that the CD97, a member of the epidermal growth factor 7-transmembrane family, and its cellular ligand decay accelerating factor (DAF) both play important roles in tumor dedifferentiation, migration, invasiveness, and metastasis. However, the roles of CD97 and DAF in human cervical squamous cell carcinoma (CSCC) have not been investigated. The purpose of this study was to observe the expression profile of CD97 and DAF in CSCC and evaluate their clinical significance. Immunohistochemistry was used to investigate the expression of CD97 and DAF proteins in 97 patients with CSCC and 53 patients with cervical intraepithelial neoplasia, a precursor lesion of CSCC. CD97 and DAF were absent or only weakly expressed in the normal epithelium of the cervix but were present in 83.5% (81/97) and 90.7% (88/97) of CSCC samples, respectively. Overexpression of CD97 was significantly associated with a high International Federation of Gynecology and Obstetrics stage (P=0.010) and lymph node metastasis (P=0.026). The majority of CSCCs, irrespective of staging/grading classification, displayed strong DAF immunostaining. Kaplan-Meier survival analysis revealed that overexpression of CD97 was associated with a worse prognosis. Multivariate analyses showed that the International Federation of Gynecology and Obstetrics stage (P=0.000), lymph node metastasis (P=0.004), and CD97 expression (P=0.040) were independent risk factors for overall survival. The present study suggested that the expressions of CD97 and DAF were both upregulated in CSCC. The expression level of CD97 in CSCC was associated with the severity of the tumor. Furthermore, CD97 might be an independent poor prognostic factor for CSCC patients. PMID:26107567

  9. Promoter Methylation of PTEN Is a Significant Prognostic Factor in Melanoma Survival.

    PubMed

    Roh, Mi Ryung; Gupta, Sameer; Park, Kyu-Hyun; Chung, Kee Yang; Lauss, Martin; Flaherty, Keith T; Jönsson, Göran; Rha, Sun Young; Tsao, Hensin

    2016-05-01

    Structural compromise of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), occurs in 10% of melanoma specimens, and loss of PTEN expression through DNA methylation of the PTEN promoter region has also been reported in a number of other malignancies. However, the role of PTEN promoter methylation in melanoma is not well understood. We thus sought to elucidate the prevalence of PTEN promoter methylation in melanoma specimens, its relationship to clinical features, and its impact on the outcome of patients with melanoma. PTEN promoter methylation data were acquired from an archived primary Korean melanoma cohort (KMC) of 158 patients and, for validation, 234 patients from The Cancer Genome Atlas melanoma (TCGA-MEL) cohort. Hierarchical clustering was performed to identify PTEN "high methylated" and "low methylated" samples. Subsequently, differences in clinical features and outcomes based on PTEN promoter methylation status were then analyzed using SPSS and R. In the KMC, all tumors were acquired from primary tumors and 65.7% (n = 105) were acral or mucosal by site, whereas in the TCGA-MEL cohort, 90.5% of the tumors were from regional lymph node and distant metastatic lesions. Overall, 17.7% and 45.7% of the specimens harbored BRAF mutations in the KMC and TCGA-MEL cohort, respectively. Neuroblastoma RAS viral oncogene homolog was mutated in 12.2% and 26.9% of the tumors in the KMC and TCGA-MEL cohort, respectively. In the KMC, 31 cases (19.6%) were included in the high methylated group versus 142 cases (60.7%) in the TCGA-MEL cohort (P < 0.001). Multivariate Cox-regression analysis revealed promoter methylation of PTEN to be an independent negative prognostic factor for survival in both the KMC (hazard ratio 3.76, 95% confidence interval = 1.24-11.12, P = 0.017) and TCGA-MEL cohort (HR 1.88, 95% confidence interval = 1.13-3.12, P = 0.015). Our results indicate that PTEN promoter methylation is an independent predictor for impaired survival in

  10. Prognostic significance of transient myocardial ischaemia after first acute myocardial infarction: five year follow up study.

    PubMed Central

    Mickley, H.; Nielsen, J. R.; Berning, J.; Junker, A.; Møller, M.

    1995-01-01

    OBJECTIVE--To assess the five year prognostic significance of transient myocardial ischaemia on ambulatory monitoring after a first acute myocardial infarction, and to compare the diagnostic and long term prognostic value of ambulatory ST segment monitoring, maximal exercise testing, and echocardiography in patients with documented ischaemic heart disease. DESIGN--Prospective study. SETTING--Cardiology department of a teaching hospital. PATIENTS--123 consecutive men aged under 70 who were able to perform predischarge maximal exercise testing. INTERVENTIONS--Echocardiography two days before discharge (left ventricular ejection fraction), maximal bicycle ergometric testing one day before discharge (ST segment depression, angina, blood pressure, heart rate), and ambulatory ST segment monitoring (transient myocardial ischaemia) started at hospital discharge a mean of 11 (SD 5) days after infarction. MAIN OUTCOME MEASURES--Relation of ambulatory ST segment depression, exercise test variables, and left ventricular ejection fraction to subsequent objective (cardiac death or myocardial infarction) or subjective (need for coronary revascularisation) events. RESULTS--23 of the 123 patients had episodes of transient ST segment depression, of which 98% were silent. Over a mean of 5 (range 4 to 6) years of follow up, patients with ambulatory ischaemia were no more likely to have objective end points than patients without ischaemic episodes. If, however, subjective events were included an association between transient ST segment depression and an adverse long term outcome was found (Kaplan-Meier analysis; P = 0.004). The presence of exercise induced angina identified a similar proportion of patients with a poor prognosis (Kaplan-Meier analysis; P < 0.004). Both exertional angina and ambulatory ST segment depression had high specificity but poor sensitivity. The presence of exercise induced ST segment depression was of no value in predicting combined cardiac events. Indeed

  11. Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: A meta-analysis

    PubMed Central

    Yang, Jian-Jun; Hu, Zhi-Gao; Shi, Wu-Xiang; Deng, Te; He, Song-Qing; Yuan, Sheng-Guang

    2015-01-01

    AIM: To conduct a meta-analysis evaluating the association between the peripheral blood neutrophil to lymphocyte ratio (NLR) and the outcome of patients with pancreatic cancer. METHODS: Studies evaluating the relationship between the peripheral blood NLR and outcome of patients with pancreatic cancer published up to May 2014 were searched using electronic databases, including PubMed, Web of Science, Embase and Ovid. A meta-analysis was performed to pool the hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) using either a fixed-effects model or a random-effects model to quantitatively assess the prognostic value of NLR and its association with clinicopathological parameters. RESULTS: Eleven studies containing a total of 1804 patients were eligible according to our selection criteria, and combined hazard ratios indicated that high NLR was a poor prognostic marker for pancreatic cancer patients because it had an unfavorable impact on the overall survival (OS) (HR = 2.61, 95%CI: 1.68-4.06, P = 0.000) and cancer specific survival (HR = 1.66, 95%CI: 1.08-2.57, P = 0.021). Subgroup analysis revealed that high NLR was associated with poor OS in patients with mixed treatment (HR = 4.36, 95%CI: 2.50-7.61, P = 0.000), chemotherapy (HR = 2.08, 95%CI: 1.49-2.9, P = 0.000), or surgical resection (HR = 1.2, 95%CI: 1.00-1.44, P = 0.048). Additionally, high NLR was significantly correlated with tumor metastasis (OR = 1.69, 95%CI: 1.10-2.59, P = 0.016), poor tumor differentiation (OR = 2.75, 95%CI: 1.19-6.36, P = 0.016), poor performance status (OR = 2.56, 95%CI: 1.63-4.03, P = 0.000), high cancer antigen 199 (OR = 2.62, 95%CI: 1.49-4.60, P = 0.000), high C-reactive protein (OR = 4.32, 95%CI: 2.71-6.87, P = 0.000), and low albumin (OR = 3.56, 95%CI: 1.37-9.27, P = 0.009). CONCLUSION: High peripheral blood NLR suggested a poor prognosis for patients with pancreatic cancer, and it could be a novel marker of survival evaluation and could help clinicians

  12. Prognostic significance of electrocardiographic findings in angina at rest. Therapeutic implications.

    PubMed Central

    Demoulin, J C; Bertholet, M; Chevigne, M; Legrand, V; Renier, J; Soumagne, D; Soyeur, D; Limet, R; Kulbertus, H

    1981-01-01

    Ninety-five patients with angina at rest were observed in the coronary care unit. Eighty-one per cent presented concomitantly or had previously presented some other manifestations of coronary artery disease. These patients were divided into two subgroups. In subgroup 1 (40 patients), episodes of non-exertional angina were associated with a pattern of hyperacute subepicardial injury and, frequently, with ventricular arrhythmias. In subgroup 2 (55 patients), the episodes of angina at rest were attended by horizontal ST depression, isolated T wave inversion, or trivial ST-T changes. Coronary angiographic findings were similar in both subgroups. Symptoms regressed in only 9% of patients in subgroup 1 while they were receiving beta-receptor antagonists, whereas amiodarone alone or amiodarone with nifedipine was successful in 58%. Of these patients, 25% developed a myocardial infarction shortly after admission. In subgroup 2 patients, beta-blockers were successful in 61%. Amiodarone isolated or associated with nifedipine was successful in 55% of the patients in whom it was tried. Only 5% of patients in this subgroup developed a myocardial infarction during their hospital stay. It is concluded that: (1) observation of the electrocardiogram during spontaneous angina in patients with known atherosclerotic coronary heart disease may be of prognostic significance and may influence therapeutic decision. (2) Amiodarone by virtue of its anginal and antiarrhythmic properties may be particularly useful in the treatment of non-exertional angina. PMID:6117297

  13. Prognostic significance of normal quantitative planar thallium-201 stress scintigraphy in patients with chest pain

    SciTech Connect

    Wackers, F.J.; Russo, D.J.; Russo, D.; Clements, J.P.

    1985-07-01

    The prognostic significance of normal quantitative planar thallium-201 stress scintigraphy was evaluated in patients with a chest pain syndrome. The prevalence of cardiac events during follow-up was related to the pretest (that is, before stress scintigraphy) likelihood of coronary artery disease determined on the basis of symptoms, age, sex and stress electrocardiography. In a consecutive series of 344 patients who had adequate thallium-201 stress scintigrams, 95 had unequivocally normal studies by quantitative analysis. The pretest likelihood of coronary artery disease in the 95 patients had a bimodal distribution. During a mean follow-up period of 22 +/- 3 months, no patient died. Three patients (3%) had a cardiac event: two of these patients (pretest likelihood of coronary artery disease 54 and 94%) had a nonfatal myocardial infarction 8 and 22 months, respectively, after stress scintigraphy, and one patient (pretest likelihood 98%) underwent percutaneous transluminal coronary angioplasty 16 months after stress scintigraphy for persisting anginal complaints. Three patients were lost to follow-up; all three had a low pretest likelihood of coronary artery disease. It is concluded that patients with chest pain and normal findings on quantitative thallium-201 scintigraphy have an excellent prognosis. Cardiac events are rare (infarction rate 1% per year) and occur in patients with a moderate to high pretest likelihood of coronary artery disease.

  14. Prognostic significance of XIAP expression in DLBCL and effect of its inhibition on AKT signalling.

    PubMed

    Hussain, Azhar R; Uddin, Shahab; Ahmed, Maqbool; Bu, Rong; Ahmed, Saeeda O; Abubaker, Jehad; Sultana, Mehar; Ajarim, Dahish; Al-Dayel, Fouad; Bavi, Prashant P; Al-Kuraya, Khawla S

    2010-10-01

    The inhibitor of apoptosis protein (IAP) family member X-linked inhibitor of apoptosis protein (XIAP) is essential for cell survival in lymphoma. However, the role of XIAP overexpression in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Therefore, we analysed the expression of XIAP protein and its clinicopathological correlation in a large cohort of DLBCLs by immunohistochemistry in a tissue micro-array format. XIAP was found to be overexpressed in 55% of DLBCLs and significantly associated with poor clinical outcome (p = 0.0421). To further elucidate the role of XIAP in DLBCL and the inter-relationship with PI3-kinase/AKT signalling, we conducted several in vitro studies using a panel of DLBCL cell lines. We found that pharmacological inhibition of XIAP led to caspase-dependent apoptosis in DLBCL cells. We also detected an inter-relationship between XIAP expression and activated AKT in DLBCL cells that may explain cellular resistance to PI3-kinase/AKT inhibition-mediated apoptosis. Finally, this anti-apoptotic effect was overcome by simultaneous pharmacological inhibition of XIAP and PI3-kinase/AKT signalling leading to a more potent synergistically induced apoptosis. In summary, our data suggest that XIAP expression is a poor prognostic factor in DLBCL and the XIAP-AKT relationship should be explored further as a potential therapeutic target in DLBCL. PMID:20632385

  15. Prognostic significance of matrix metalloproteinase 7 immunohistochemical expression in colorectal cancer: a meta-analysis

    PubMed Central

    Chen, Haiyan; Hu, Yeting; Xiang, Weibo; Cai, Yibo; Wang, Zhanhuai; Xiao, Qian; Liu, Yue; Li, Qiong; Ding, Kefeng

    2015-01-01

    Matrix metalloproteinase 7 (MMP-7) was speculated to have a key role in the development and progression of human cancer. Considerable studies investigated the relationship between its expression and survival in colorectal cancer (CRC), but inconsistent results were obtained. The clinical significance of MMP-7 overexpression in CRC remains controversial. Therefore, in this article, we conducted a meta-analysis to analyze the prognostic value of MMP-7 in CRC. We searched studies in PubMed, Medline, and Web of Science databases until August 2014 to find relevant studies. A total of six high-quality studies met the inclusion criteria and 1631 patients were included in our study. Combined hazard ratios (HRs) suggested that MMP-7 overexpression had an unfavorable impact on overall survival (HR = 1.83, 95% CI: 1.24-2.71). Subgroup and sensitivity analyses further validated the role of MMP-7 as a predictor for prognosis. In conclusion, MMP-7 overexpression detected by immunohistochemistry indicated worse prognosis in CRC and may help to guide clinical therapy. PMID:26064217

  16. Expression, prognostic significance and mutational analysis of protein tyrosine phosphatase SHP-1 in chronic myeloid leukemia.

    PubMed

    Papadopoulou, Vasiliki; Kontandreopoulou, Elina; Panayiotidis, Panayiotis; Roumelioti, Maria; Angelopoulou, Maria; Kyriazopoulou, Lydia; Diamantopoulos, Panagiotis T; Vaiopoulos, George; Variami, Eleni; Kotsianidis, Ioannis; Athina Viniou, Nora

    2016-05-01

    The protein tyrosine phosphatase SHP-1 dephosphorylates BCR-ABL1, thereby serving as a potential control mechanism of BCR-ABL1 kinase activity. Pathways regulating SHP-1 expression, which could be exploited in the therapeutics of TKI-resistant chronic myeloid leukemia (CML), remain unknown. Moreover, the questions of whether there is any kind of SHP-1 deregulation in CML, contributing to disease initiation or evolution, as well as the question of prognostic significance of SHP-1, have not been definitively answered. This study shows moderately lower SHP-1 mRNA expression in chronic phase CML patients in comparison to healthy individuals and no change in SHP-1 mRNA levels after successful TKI treatment. Mutational analysis of the aminoterminal and phosphatase domains of SHP-1 in patients did not reveal genetic lesions. This study also found no correlation of SHP-1 expression at diagnosis with response to treatment, although a trend for lower SHP-1 expression was noted in the very small non-responders' group of the 3-month therapeutic milestone. PMID:26373709

  17. Complex karyotype in mantle cell lymphoma is a strong prognostic factor for the time to treatment and overall survival, independent of the MCL international prognostic index.

    PubMed

    Sarkozy, Clémentine; Terré, Christine; Jardin, Fabrice; Radford, Isabelle; Roche-Lestienne, Catherine; Penther, Dominique; Bastard, Christian; Rigaudeau, Sophie; Pilorge, Sylvain; Morschhauser, Franck; Bouscary, Didier; Delarue, Richard; Farhat, Hassan; Rousselot, Philippe; Hermine, Olivier; Tilly, Hervé; Chevret, Sylvie; Castaigne, Sylvie

    2014-01-01

    Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an "indolent" evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision. We aimed to evaluate the prognostic impact of these additional abnormalities detected by conventional cytogenetic testing, as well as their relationships with the clinical characteristics and their value in identifying iMCL. All consecutive MCL cases diagnosed between 1995 and 2011 at four institutions were retrospectively selected on the basis of an informative karyotype with a t(11;14) translocation at the time of diagnosis. A total of 125 patients were included and followed for an actual median time of 35 months. The median overall survival (OS) and survival without treatment (TFS) were 73.7 and 1.3 months, respectively. In multivariable Cox models, a high mantle cell lymphoma international prognostic index score, a complex karyotype, and blastoid morphology were independently associated with a shortened OS. Spleen enlargement, nodal presentation, extra-hematological involvement, and complex karyotypes were associated with shorter TFS. A score based on these factors allowed for the identification of "indolent" patients (median TFS 107 months) from other patients (median TFS: 1 month). In conclusion, in this multicentric cohort of MCL patients, a complex karyotype was associated with a shorter survival time and allowed for the identification of iMCL at the time of diagnosis. PMID:24249260

  18. The prognostic significance of left ventricular ejection fraction in patients with advanced cancer treated in phase I clinical trials

    PubMed Central

    Said, R.; Banchs, J.; Wheler, J.; Hess, K. R.; Falchook, G.; Fu, S.; Naing, A.; Hong, D.; Piha-Paul, S.; Ye, Y.; Yeh, E.; Wolff, R. A.; Tsimberidou, A. M.

    2014-01-01

    Background New targeted agents may cause acute cardiac events. The purpose of our study was to investigate the incidence and the prognostic significance of left ventricular ejection fraction (LVEF) in phase I trials. Patients and methods Between October 2008 and September 2011, the records of 1166 consecutive patients with advanced cancer treated in the Phase I Clinic who underwent echocardiography were retrospectively reviewed. Results Most of the patients were White (78%), and the most common tumor types were colorectal cancer and melanoma. Of 1166 patients, 177 (15.2%) patients had an LVEF of <50%. No difference in overall survival (OS) between patients with LVEF ≥ 50% and patients with LVEF < 50% was seen (median OS 7.4 versus 7.0 months, P = 0.84). Patients with LVEF ≤ 35% had shorter survival compared with those with LVEF between 35% and 50% (median 4.2 versus 8.0 months; P = 0.005). In multivariate analysis of patients with LVEF < 50%, independent factors predicting longer survival were LVEF > 35%, ≤2 prior systemic therapies, ≤2 metastatic sites, and normal lactate dehydrogenase and albumin levels. Conclusion Echocardiography would improve patient selection for enrollment in phase I clinical trials. These data suggest that it is safe to treat patients with LVEF between 35% and 50%. PMID:24356639

  19. Clinical significance of pre-operative neutrophil lymphocyte ratio and platelet lymphocyte ratio as prognostic factors for patients with colorectal cancer

    PubMed Central

    ZOU, ZHEN-YU; LIU, HAI-LIANG; NING, NING; LI, SONG-YAN; DU, XIAO-HUI; LI, RONG

    2016-01-01

    The present study aimed to investigate the independent prognostic values of the pre-operative neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in patients with colorectal cancer (CRC). The present study retrospectively analyzed the data of 216 patients with CRC from a single hospital. The clinicopathological characteristics of the patients were compared and prognostic factors were evaluated. NLR and PLR were associated with tumor differentiation status and the tumor diameter, respectively, and PLR was also associated with the primary tumor classification (T classification). Furthermore, NLR and PLR were positively associated with each other (R2=0.5368; P<0.0001). Univariate analyses indicated that stage II and III patients with a high NLR (≥4.98; P<0.001) or PLR (≥246.36; P<0.001) possessed a significantly poorer 5-year OS rate compared with those with a low NLR or PLR. Post-operative adjuvant chemotherapy improved the 5-year OS rate in patients with a high NLR or PLR. Multivariate analyses indicated that NLR and PLR were independent prognostic factors [NLR, relative risk (RR)=4.074 and P<0.001; PLR, RR=2.029 and P=0.029] in patients with CRC, and were associated with the T classification, lymph node metastasis and post-operative adjuvant chemotherapy response of patients. Additionally, the area under the curve (AUC) was 0.748 for NLR (95% CI, 0.684–0.804; P<0.0001) and 0.690 for PLR (95% CI, 0.623–0.751; P<0.0001). The RR and AUC indicated that NLR was the superior predictive factor in patients with CRC. In conclusion, the pre-operative NLR and PLR were significant independent prognostic factors in patients with CRC, and NLR was more effective as a prognostic marker compared with PLR. Adjuvant chemotherapy appeared to be more effective in CRC patients with a higher NLR or PLR. PMID:26998156

  20. Transcriptomic analysis of aggressive meningiomas identifies PTTG1 and LEPR as prognostic biomarkers independent of WHO grade

    PubMed Central

    Jungk, Christine; Sahm, Felix; Ull, Anna Theresa; Warta, Rolf; Lamszus, Katrin; Gousias, Konstantinos; Ketter, Ralf; Roesch, Saskia; Rapp, Carmen; Schefzyk, Sebastian; Urbschat, Steffi; Lahrmann, Bernd; Kessler, Almuth F.; Löhr, Mario; Senft, Christian; Grabe, Niels; Reuss, David; Beckhove, Philipp; Westphal, Manfred; von Deimling, Andreas; Unterberg, Andreas

    2016-01-01

    Meningiomas are frequent central nervous system tumors. Although most meningiomas are benign (WHO grade I) and curable by surgery, WHO grade II and III tumors remain therapeutically challenging due to frequent recurrence. Interestingly, relapse also occurs in some WHO grade I meningiomas. Hence, we investigated the transcriptional features defining aggressive (recurrent, malignantly progressing or WHO grade III) meningiomas in 144 cases. Meningiomas were categorized into non-recurrent (NR), recurrent (R), and tumors undergoing malignant progression (M) in addition to their WHO grade. Unsupervised transcriptomic analysis in 62 meningiomas revealed transcriptional profiles lining up according to WHO grade and clinical subgroup. Notably aggressive subgroups (R+M tumors and WHO grade III) shared a large set of differentially expressed genes (n=332; p<0.01, FC>1.25). In an independent multicenter validation set (n=82), differential expression of 10 genes between WHO grades was confirmed. Additionally, among WHO grade I tumors differential expression between NR and aggressive R+M tumors was affirmed for PTTG1, AURKB, ECT2, UBE2C and PRC1, while MN1 and LEPR discriminated between NR and R+M WHO grade II tumors. Univariate survival analysis revealed a significant association with progression-free survival for PTTG1, LEPR, MN1, ECT2, PRC1, COX10, UBE2C expression, while multivariate analysis identified a prediction for PTTG1 and LEPR mRNA expression independent of gender, WHO grade and extent of resection. Finally, stainings of PTTG1 and LEPR confirmed malignancy-associated protein expression changes. In conclusion, based on the so far largest study sample of WHO grade III and recurrent meningiomas we report a comprehensive transcriptional landscape and two prognostic markers. PMID:26894859

  1. Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype

    PubMed Central

    Poiré, Xavier; Moser, Barry K.; Gallagher, Robert E.; Laumann, Kristina; Bloomfield, Clara D.; Powell, Bayard L.; Koval, Gregory; Gulati, Kabir; Holowka, Nicholas; Larson, Richard A.; Tallman, Martin S.; Appelbaum, Frederick R.; Sher, Dorie; Willman, Cheryl; Paietta, Elisabeth; Stock, Wendy

    2014-01-01

    The addition of arsenic trioxide (ATO) to frontline therapy of acute promyelocytic leukemia (APL) has been shown to result in significant improvements in disease-free survival (DFS). FLT3 mutations are frequently observed in APL, but its prognostic significance remains unclear. We analyzed 245 newly diagnosed adult patients with APL treated on intergroup trial C9710 and evaluated previously defined biological and prognostic factors and their relationship to FLT3 mutations and to additional karyotypic abnormalities. FLT3 mutations were found in 48% of patients, including 31% with an internal tandem duplication (FLT3-ITD), 14% with a point mutation (FLT3-D835) and 2% with both mutations. The FLT3-ITD mutant level was uniformly low, <0.5. Neither FLT3 mutation had an impact on remission rate, induction death rate, DFS or overall survival (OS). The addition of ATO consolidation improved outcomes regardless of FLT3 mutation type or level, initial white blood cell count, PML–RARA isoform type or transcript level. The presence of a complex karyotype was strongly associated with an inferior OS independently of post-remission treatment. In conclusion, the addition of ATO to frontline therapy overcomes the impact of previously described adverse prognostic factors including FLT3 mutations. However, complex karyotype is strongly associated with an inferior OS despite ATO therapy. PMID:24160850

  2. Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype.

    PubMed

    Poiré, Xavier; Moser, Barry K; Gallagher, Robert E; Laumann, Kristina; Bloomfield, Clara D; Powell, Bayard L; Koval, Gregory; Gulati, Kabir; Holowka, Nicholas; Larson, Richard A; Tallman, Martin S; Appelbaum, Frederick R; Sher, Dorie; Willman, Cheryl; Paietta, Elisabeth; Stock, Wendy

    2014-07-01

    The addition of arsenic trioxide (ATO) to frontline therapy of acute promyelocytic leukemia (APL) has been shown to result in significant improvements in disease-free survival (DFS). FLT3 mutations are frequently observed in APL, but its prognostic significance remains unclear. We analyzed 245 newly diagnosed adult patients with APL treated on intergroup trial C9710 and evaluated previously defined biological and prognostic factors and their relationship to FLT3 mutations and to additional karyotypic abnormalities. FLT3 mutations were found in 48% of patients, including 31% with an internal tandem duplication (FLT3-ITD), 14% with a point mutation (FLT3-D835) and 2% with both mutations. The FLT3-ITD mutant level was uniformly low, < 0.5. Neither FLT3 mutation had an impact on remission rate, induction death rate, DFS or overall survival (OS). The addition of ATO consolidation improved outcomes regardless of FLT3 mutation type or level, initial white blood cell count, PML-RARA isoform type or transcript level. The presence of a complex karyotype was strongly associated with an inferior OS independently of post-remission treatment. In conclusion, the addition of ATO to frontline therapy overcomes the impact of previously described adverse prognostic factors including FLT3 mutations. However, complex karyotype is strongly associated with an inferior OS despite ATO therapy. PMID:24160850

  3. ATPase inhibitory factor 1 expression is an independent prognostic factor in non-small cell lung cancer

    PubMed Central

    Gao, Yi-Xing; Chen, Lu; Hu, Xu-Gang; Wu, Hai-Bo; Cui, You-Hong; Zhang, Xia; Wang, Yan; Liu, Xin-Dong; Bian, Xiu-Wu

    2016-01-01

    ATPase inhibitory factor 1 (IF1), an inhibitor of the mitochondrial H+-adenosine triphosphate (ATP) synthase, is putatively involved in tumor progression. This study aimed to evaluate the expression levels of IF1 in non-small cell lung cancer (NSCLC) and the prognostic value for the patients. IF1 protein expression levels were detected in 149 cases of NSCLC by using immunohistochemistry. Kaplan-Meier analysis showed that NSCLC patients with high expression of IF1 possessed poorer outcome than those with low expression of IF1 (P=0.007). Moreover, IF1 was also prognostic in the patients with early stages (stage I/II) (P=0.042) and low grade (grade I/II) (P=0.002). Multivariable Cox-regression analysis showed that high expression of IF1 (HR=1.67, P=0.034), tumor size (HR=1.79, P=0.001), and lymph node metastasis (HR=2.66, P=0.000) were independent indicators for NSCLC patients. In conclusion, our study demonstrated that elevated expression of IF1 may associated with lymph node metastasis of NSCLC and served as an independent prognostic and recurrent indicator for the patients. PMID:27294006

  4. Prognostic significance of Bcl-xL expression and efficacy of Bcl-xL targeting therapy in urothelial carcinoma

    PubMed Central

    Yoshimine, S; Kikuchi, E; Kosaka, T; Mikami, S; Miyajima, A; Okada, Y; Oya, M

    2013-01-01

    Background: Bcl-xL has an important role in the control of cell death through its inhibition of apoptosis. The aim of this study was to investigate the clinicopathological significance of Bcl-xL in upper urinary tract urothelial carcinoma (UTUC) and the therapeutic effect of targeting Bcl-xL protein in urothelial carcinoma (UC) cells. Methods: We evaluated the immunohistochemical expression of Bcl-xL in 175 UTUC patients to determine the clinical role of Bcl-xL expression in clinical outcome. We used bafilomycin A1 (BMA) as a specific inhibitor of Bcl-xL to examine the biological effects in UC cells in vitro and in vivo. Results: Immunohistochemical analysis of Bcl-xL expression revealed that patients with a high Bcl-xL score had a significantly lower 5-year cancer-specific survival (CSS) rate (53.2%) than those with a low Bcl-xL score (77.2%) (P=0.0011). Multivariate analysis indicated that a high Bcl-xL score was an independent prognostic factor of CSS (P=0.023). BMA inhibited UMUC-3 cell proliferation in vitro by induction of apoptosis. Treatment with BMA significantly inhibited tumour growth in UMUC-3 tumours in this mouse xenograft model accompanied by an elevated apoptosis induction. Conclusion: Bcl-xL appears to be a significant molecular marker for the prognosis of UTUCs. Targeting Bcl-xL may be a promising therapeutic strategy for patients with UC. PMID:23674090

  5. Expression and Prognostic Significance of a Panel of Tissue Hypoxia Markers in Head-and-Neck Squamous Cell Carcinomas

    SciTech Connect

    Le, Quynh-Thu Kong, Christina; Lavori, Phillip W.; O'Byrne, Ken; Erler, Janine T.; Huang Xin; Chen Yijun; Cao Hongbin; Tibshirani, Robert; Denko, Nic; Giaccia, Amato J.; Koong, Albert C.

    2007-09-01

    Purpose: To investigate the expression pattern of hypoxia-induced proteins identified as being involved in malignant progression of head-and-neck squamous cell carcinoma (HNSCC) and to determine their relationship to tumor pO{sub 2} and prognosis. Methods and Materials: We performed immunohistochemical staining of hypoxia-induced proteins (carbonic anhydrase IX [CA IX], BNIP3L, connective tissue growth factor, osteopontin, ephrin A1, hypoxia inducible gene-2, dihydrofolate reductase, galectin-1, I{kappa}B kinase {beta}, and lysyl oxidase) on tumor tissue arrays of 101 HNSCC patients with pretreatment pO{sub 2} measurements. Analysis of variance and Fisher's exact tests were used to evaluate the relationship between marker expression, tumor pO{sub 2}, and CA IX staining. Cox proportional hazard model and log-rank tests were used to determine the relationship between markers and prognosis. Results: Osteopontin expression correlated with tumor pO{sub 2} (Eppendorf measurements) (p = 0.04). However, there was a strong correlation between lysyl oxidase, ephrin A1, and galectin-1 and CA IX staining. These markers also predicted for cancer-specific survival and overall survival on univariate analysis. A hypoxia score of 0-5 was assigned to each patient, on the basis of the presence of strong staining for these markers, whereby a higher score signifies increased marker expression. On multivariate analysis, increasing hypoxia score was an independent prognostic factor for cancer-specific survival (p = 0.015) and was borderline significant for overall survival (p = 0.057) when adjusted for other independent predictors of outcomes (hemoglobin and age). Conclusions: We identified a panel of hypoxia-related tissue markers that correlates with treatment outcomes in HNSCC. Validation of these markers will be needed to determine their utility in identifying patients for hypoxia-targeted therapy.

  6. Prognostic significance of interleukin-17 in solid tumors: a meta-analysis

    PubMed Central

    Zeng, Yunhui; Zhang, Qiongwen; Wang, Hong; Lu, Minxun; Kong, Hongyu; Zhang, Yingyi; Shi, Huashan

    2015-01-01

    Background: The prognostic significance of intratumoral and peripheral interleukin-17 (IL-17) in tumors has been studied worldwide during these years, providing un-uniformed conclusions. Methods: We conducted a meta-analysis of published literatures that evaluated the correlation between IL-17 and clinical staging, overall survival (OS) and/or disease free survival (DFS). Results: A total of 28 studies enrolling 2902 patients were included. For the overall population, a high expression of IL-17 was found significantly correlated with worse DFS (HR = 1.59, 95% CI: 1.24-2.03) in patients with solid tumors. For gastrointestinal tumors, patients with IL-17 high seemed to have worse OS (HR = 1.85, 95% CI: 1.24-2.75) and DFS (HR = 2.41, 95% CI: 1.98-2.92). Sub-group meta-analysis revealed that IL-17 indicated late clinical staging in non-small cell lung cancer (NSCLC) patients (HR = 2.33, 95% CI: 1.25-4.32), on the other hand, early clinical staging in patients with esophageal squamous carcinoma (HR = 0.63, 95% CI: 0.42-0.94). Negative impacts of IL-17 on OS were shown in patients with hepatocellular carcinoma (HCC) (HR = 1.87, 95% CI: 1.23-2.84) or NSCLC (HR = 1.55, 95% CI: 1.02-2.35). However, positive impacts on OS were provided in patients with esophageal squamous carcinoma (HR = 0.65, 95% CI: 0.50-0.84). Besides, a high expression of IL-17 predicted better DFS in ovarian cancer patients (HR = 0.33, 95% CI: 0.11-1.00). Conclusions: Our meta-analysis revealed that IL-17 might correlate with poor OS and DFS in gastrointestinal tumors. Specifically, IL-17 was a detrimental factor for HCC and NSCLC patients, whereas a beneficial factor for patients with esophageal squamous carcinoma and ovarian cancer. PMID:26379842

  7. Nutritional and prognostic significance of insulin-like growth factor 1 in patients with liver cirrhosis.

    PubMed

    Caregaro, L; Alberino, F; Amodio, P; Merkel, C; Angeli, P; Plebani, M; Bolognesi, M; Gatta, A

    1997-03-01

    Most of the traditional parameters for nutrition assessment have important limitations in patients with chronic liver disease. Insulin-like growth factor 1 (IGF-1) has been found to be regulated by nutrition and proposed as a nutritional marker. Its nutritional significance in patients with liver cirrhosis, however, has not been investigated. Serum IGF-1 as well as traditional anthropometric, visceral, and immunologic parameters were evaluated in 64 hospitalized cirrhotics, followed up clinically for 2 y. IGF-1Z-score averaged -2.16 +/- 1.08 and inversely correlated with Child-Pugh score (P < 0.01), the most reliable composite score reflecting the severity of liver disease. IGF-1Z-score was not different in patients with or without signs of energy malnutrition, as defined by values of midarm muscle circumference (MAMC) and/or triceps skinfold (TSF) < 5th percentile. Moreover, IGF-1Z-score did not correlate with MAMC or TSF. Despite its correlation with all visceral proteins, the reduction of IGF-1 was much greater and more frequent than that of visceral proteins. Patients with IGF-1Z-score < median values (-2.5) showed lower long-term survival rates compared with patients with IGF-1Z-score > -2.5 (P < 0.01). These data indicate that serum IGF-1 is not related to energy malnutrition in cirrhotic patients, while it appears to be a good predictor of survival and an early marker of liver dysfunction. Multiple factors, most of which are related to the severity of the liver disease, may contribute to the reduction of IGF-1. This multifactorial pathogenesis probably accounts for its prognostic significance. PMID:9131676

  8. Prognostic Significance of EBV Latent Membrane Protein 1 Expression in Lymphomas: Evidence from 15 Studies

    PubMed Central

    Mao, Yuan; Lu, Mei Ping; Lin, Hong; Zhang, Da Wei; Liu, Ying; Li, Qing Dong; Lv, Zhi Gang; Xu, Jia Ren; Chen, Ren Jie; Zhu, Jin

    2013-01-01

    Background Epstein-Barr virus (EBV) infection has been associated with lymphoma development. EBV latent membrane protein 1 (LMP1) is essential for EBV-mediated transformation and progression of different human cells, including lymphocytes. This meta-analysis investigated LMP1 expression with prognosis of patients with lymphoma. Methods The electronic databases of PubMed, Embase, and Chinese Biomedicine Databases were searched. There were 15 published studies available for a random effects model analysis. Quality assessment was performed using the Newcastle-Ottawa Quality Assessment Scale for cohort studies. A funnel plot was used to investigate publication bias, and sources of heterogeneity were identified by meta-regression analysis. The combined hazard ratios (HR) and their corresponding 95% confidence intervals of LMP1 expression were calculated by comparison to the overall survival. Results Overall, there was no statistical significance found between LMP1 expression and survival of lymphoma patients (HR 1.25 [95% CI, 0.92–1.68]). In subgroup analyses, LMP1 expression was associated with survival in patients with non-Hodgkin lymphoma (NHL) (HR  = 1.84, 95% CI: 1.02–3.34), but not with survival of patients with Hodgkin disease (HD) (HR  =  1.03, 95% CI: 0.74–1.44). In addition, significant heterogeneity was present and the meta-regression revealed that the outcome of analysis was mainly influenced by the cutoff value. Conclusions This meta-analysis demonstrated that LMP1 expression appears to be an unfavorable prognostic factor for overall survival of NHL patients. The data suggested that EBV infection and LMP1 expression may be an important factor for NHL development or progression. PMID:23613723

  9. Prognostic significance of radionuclide-assessed diastolic function in hypertrophic cardiomyopathy

    SciTech Connect

    Chikamori, T.; Dickie, S.; Poloniecki, J.D.; Myers, M.J.; Lavender, J.P.; McKenna, W.J. )

    1990-02-15

    To evaluate the prognostic significance of diastolic function in hypertrophic cardiomyopathy (HC), technetium-99m gated equilibrium radionuclide angiography, acquired in list mode, was performed in 161 patients. Five diastolic indexes were calculated. During 3.0 +/- 1.9 years, 13 patients had disease-related deaths. With univariate analysis, these patients were younger (29 +/- 20 vs 42 +/- 16 years; p less than 0.05), had a higher incidence of syncope (p less than 0.025), dyspnea (p less than 0.001), reduced peak filling rate (2.9 +/- 0.9 vs 3.4 +/- 1.0 end-diastolic volume/s; p = 0.09) with increased relative filling volume during the rapid filling period (80 +/- 7 vs 75 +/- 12%; p = 0.06) and decreased atrial contribution (17 +/- 7 vs 22 +/- 11%; p = 0.07). Stepwise discriminant analysis revealed that young age at diagnosis, syncope at diagnosis, reduced peak ejection rate, positive family history, reduced peak filling rate, increased relative filling volume by peak filling rate and concentric left ventricular hypertrophy were the most statistically significant (p = 0.0001) predictors of disease-related death (sensitivity 92%, specificity 76%, accuracy 77%, positive predictive value 25%). Discriminant analysis excluding the diastolic indexes, however, showed similar predictability (sensitivity 92%, specificity 76%, accuracy 78%, positive predictive value 26%). To obtain more homogeneous groups for analysis, patients were classified as survivors or electrically unstable, including sudden death, out-of-hospital ventricular fibrillation and nonsustained ventricular tachycardia during 48-hour ambulatory electrocardiography, and heart failure death or cardiac transplant.

  10. Immunohistochemical detection of p53 and Bcl-2 in colorectal carcinoma: no evidence for prognostic significance.

    PubMed Central

    Tollenaar, R. A.; van Krieken, J. H.; van Slooten, H. J.; Bruinvels, D. J.; Nelemans, K. M.; van den Broek, L. J.; Hermans, J.; van Dierendonck, J. H.

    1998-01-01

    To evaluate the prognostic significance of immunohistochemically detected p53 and Bcl-2 proteins in colorectal cancer, tissue sections from 238 paraffin-embedded colorectal carcinomas were immunostained for p53 (MAb DO-7 and CM-1 antiserum) and Bcl-2 (MAb Bcl-2:124). Staining patterns were assessed semiquantitatively and correlated with each other and with sex, age, tumour site, Dukes' classification, tumour differentiation, mucinous characteristics, lymphocyte and eosinophilic granulocyte infiltration, and patient survival. In our series, 35% of carcinomas showed no nuclear staining and 34% (DO-7) to 40% (CM-1) showed staining in over 30% of tumour cell nuclei. A majority of carcinomas that had been immunostained with CM-1 showed cytoplasmic staining, but this was not observed with DO-7. With respect to Bcl-2, 51% of tumours were completely negative, 32% displayed weak and 15% moderate staining; only 3% showed strong positive staining. No evidence was found for reciprocity between Bcl-2 expression and nuclear p53 accumulation. From 13 cases containing tumour-associated adenoma, four were Bcl-2 negative in premalignant and malignant cells, in another four cases these cells showed similar staining intensities and in the remaining cases only the malignant colorectal cells were Bcl-2 negative. Therefore, our data indicate that Bcl-2 is dispensable in the progression towards carcinoma. Except for an association between nuclear p53 accumulation and mucinous tumours (P = 0.01), no significant correlation was found between the clinicopathological parameters mentioned above and immunostaining pattern of (nuclear or cytoplasmic) p53 or Bcl-2. PMID:9667656

  11. Protein expression and amplification of AIB1 in human urothelial carcinoma of the bladder and overexpression of AIB1 is a new independent prognostic marker of patient survival.

    PubMed

    Luo, Jun-Hang; Xie, Dan; Liu, Meng-Zhong; Chen, Wei; Liu, Yong-Dong; Wu, Guo-Qing; Kung, Hsiang-Fu; Zeng, Yi-Xin; Guan, Xin-Yuan

    2008-06-01

    AIB1, a candidate oncogene in human breast cancer, is frequently amplified and overexpressed in several types of human cancers, but the status of AIB1 amplification and expression in urothelial carcinoma of the bladder (UC) and its clinical/prognostic significance is unclear. In our study, the methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of AIB1 in 163 primary UCs and in 30 samples of normal bladder mucosa. Overexpression of AIB1 and amplification of AIB1 was found in 32.5 and 7.0% of UCs, respectively. In univariate survival analysis of the UC cohorts, a highly significant association of overexpression of AIB1 with shortened patient survival (mean: 45.6 months vs. 59.0 months, p < 0.001, log rank test) was demonstrated. In different subsets of UC patients, overexpression of AIB1 was also a prognostic indicator in grade 1 (p = 0.007), grade 2 (p = 0.010) and grade 3 (p = 0.015) tumor patients, and in pTa (p = 0.025), pT2-4 (p = 0.004), pN0 (p < 0.001) and pT2-4/pN0 (p = 0.040) tumor patients. Importantly, AIB1 expression (p < 0.001) together with pT and pN status (p < 0.05) provided significant independent prognostic parameters in multivariate analysis. In addition, a significant correlation (p < 0.05) of overexpression of AIB1 with an increased UC labeling index of Ki-67 (a cell proliferation marker) was observed in these UCs. Thus, these findings provide evidence that an overexpression of AIB1, as detected by immunohistochemistry, is an independent molecular marker for poor prognosis (shortened survival time) of patients with UC. PMID:18246597

  12. Prognostic significance of host immune status in patients with late relapsing renal cell carcinoma treated with targeted therapy.

    PubMed

    Santoni, Matteo; Buti, Sebastiano; Conti, Alessandro; Porta, Camillo; Procopio, Giuseppe; Sternberg, Cora N; Bracarda, Sergio; Basso, Umberto; De Giorgi, Ugo; Rizzo, Mimma; Derosa, Lisa; Ortega, Cinzia; Massari, Francesco; Milella, Michele; Bersanelli, Melissa; Cerbone, Linda; Muzzonigro, Giovanni; Burattini, Luciano; Montironi, Rodolfo; Santini, Daniele; Cascinu, Stefano

    2015-12-01

    We aimed to assess the prognostic role of pretreatment neutrophilia, lymphocytopenia, and neutrophil to lymphocyte ratio (NLR) in patients treated with vascular endothelial growth factor-tyrosine kinase inhibitors (VEGFR-TKIs) for late relapsing (>5 years) metastatic renal cell carcinoma (mRCC). Data were collected from 13 Italian centers involved in the treatment of metastatic RCC. Late relapse was defined as >5 years after initial radical nephrectomy. One hundred fifty-one patients were included in this analysis. Among them, MSKCC risk score was favorable in 68 %, intermediate in 29 %, and poor in 3 %. Fifty-six patients (37 %) had NLR ≥3 at the start of VEGFR-TKI therapy (group A), while 95 had lower NLR (63 %, group B). The median overall survival (OS) was 28.8 months in group A and 68.7 months (95 % confidence interval (CI) 45.3-NA) in group B (p < 0.001). The median progression-free survival (PFS) was 15.8 months in group A and 25.1 months in group B (p = 0.03). At multivariate analysis, MSKCC risk group and NLR were independent prognostic factors for both OS and PFS. Pretreatment NLR is an independent prognostic factor for patients with late relapsing mRCC treated with first-line VEGFR-TKIs. A better characterization of baseline immunological impairment may optimize the management of this RCC subpopulation. PMID:25559290

  13. Clinical and Prognostic Significance of Preoperative Plasma Fibrinogen Levels in Patients with Operable Breast Cancer

    PubMed Central

    Lu, Xiaofei; Liu, Haixia; Li, Xiangyi; Ma, Rong

    2016-01-01

    Purpose Elevated plasma fibrinogen levels are associated with tumor progression and poor outcomes in different cancer patients. The objective of this study was to investigate the clinical and prognostic value of preoperative plasma fibrinogen levels in patients with operable breast cancer. Methods Two hundred and twenty-three patients diagnosed with breast cancer were retrospectively evaluated in this study. Plasma fibrinogen levels were examined before treatment and analyzed along with patient clinicopathological parameters, disease-free survival (DFS) and overall survival(OS). Both univariate and multivariate analyses were performed to identify the clinicopathological parameters associated with DFS and OS. Results Elevated preoperative plasma fibrinogen levels were directly associated with age of diagnose (≤47 vs. >47, p<0.001), menopause (yes vs. no, p<0.001), tumor size (T1&T2 vs.T3&T4, p = 0.033), tumor stage (Ⅰvs.Ⅱvs.Ⅲ, p = 0.034) and lymph node involvement (N = 0 vs. 1≤N≤3 vs. N≥4, p<0.001), but not with histological grade, molecular type and other Immunohistochemical parameters(ER, PR, HER2 and Ki-67). In a univariate survival analysis, tumor stage, tumor size, lymph node involvement (p<0.001/ p<0.001)and plasma fibrinogen (p<0.001/ p<0.001) levels were associated with disease-free and overall survival, but just lymph nodes involvement (p<0.001, hazard ratio [HR] = 2.9, 95% confidence interval [CI] = 1.6–5.3/ p = 0.006, HR = 3.2, 95% CI = 1.4–7.3) and plasma fibrinogen levels (p = 0.006, HR = 3.4, 95% CI = 1.4–8.3/ p = 0.002, HR = 10.1, 95% CI = 2.3–44.6) were associated with disease-free and overall survival in a multivariate survival analysis, respectively. Conclusions This study demonstrates that elevated preoperative plasma fibrinogen levels are associated with breast cancer progression and are independently associated with a poor prognosis in patients with operable breast cancer. PMID:26799214

  14. Prognostic Significance of Hypoxia-Inducible Factor Expression in Renal Cell Carcinoma

    PubMed Central

    Fan, Yang; Li, Hongzhao; Ma, Xin; Gao, Yu; Chen, Luyao; Li, Xintao; Bao, Xu; Du, Qingshan; Zhang, Yu; Zhang, Xu

    2015-01-01

    Abstract The prognostic value of hypoxia-inducible factor (HIF) in renal cell carcinoma (RCC) has been evaluated in a large number of studies, but the reports were inconsistent and remained inconclusive. Therefore, we conducted a systematic review and meta-analysis to clarify the significance of HIF expression in RCC prognosis. PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Biological Abstracts were searched for eligible studies. Hazard ratio (HR) data for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) with 95% confidence interval (CI) related to the expression status of HIF-1α or HIF-2α detected by immunohistochemistry were all extracted. Data were combined using a random- or fixed-effects model based on the corresponding inter-study heterogeneity. Subgroup analyses were also performed. A total of 14 studies composed of 1258 patients for HIF-1α evaluation and 619 patients for HIF-2α evaluation were included for further analysis. When initially analyzed as a whole, the HIF-1α expression was not significantly correlated with OS (HR 1.637, 95% CI 0.898–2.985, P = 0.108), CSS (HR 1.110, 95% CI 0.595–2.069, P = 0.744), and PFS (HR 1.113, 95% CI 0.675–1.836, P = 0.674). Similarly, HIF-2α expression was not significantly correlated with CSS (HR 1.597, 95% CI 0.667–3.824, P = 0.293) and PFS (HR 0.847, 95% CI 0.566–1.266, P = 0.417). However, subgroup analyses concerning subcellular localization of HIFs revealed that the high nuclear expression of HIF-1α was significantly associated with poor OS (HR 2.014, 95% CI 1.206–3.363, P = 0.007) and the high cytoplasmic expression of HIF -2α was significantly associated with poor CSS (HR 2.356, 95% CI 1.629–3.407, P = 0.000). The increased nuclear expression of HIF-1α and cytoplasmic expression of HIF-2α indicate unfavorable prognosis in RCC patients, which

  15. Prognostic significance of the combined expression of neutral endopeptidase and dipeptidyl peptidase IV in intrahepatic cholangiocarcinoma patients after surgery resection

    PubMed Central

    Zhu, Jianyong; Guo, XiaoDong; Qiu, Baoan; Li, Zhiyan; Xia, Nianxin; Yang, Yingxiang; Liu, Peng

    2014-01-01

    Aim The aim of this study was to investigate the relationship between the expression of neutral endopeptidase (NEP) and dipeptidyl peptidase IV (DPP IV) proteins, and the clinical significance of the two proteins in patients with intrahepatic cholangiocarcinomas (IHCC). Methods Expression patterns and subcellular localizations of NEP and DPP IV proteins in 186 primary IHCC and 60 noncancerous liver tissue specimens were detected by immunohistochemistry. Results Both the expression of NEP and DPP IV proteins in IHCC tissues were significantly higher than those in noncancerous liver tissues (both P<0.001). Of 186 patients with IHCC, 128 (68.82%) highly expressed both NEP and DPP IV proteins. In addition, the coexpression of NEP and DPP IV proteins was significantly associated with advanced tumor stage (P=0.009), positive lymph node metastasis (P=0.016) and distant metastasis (P=0.013), and the presence of recurrence (P=0.027). Moreover, Kaplan–Meier analysis showed that IHCC patients with high NEP expression, high DPP IV expression, and combined overexpression of NEP and DPP IV proteins all had poorer overall survival and early recurrence after surgery. Furthermore, Cox analysis suggested that NEP expression, DPP IV expression, and combined expression of NEP and DPP IV proteins were all independent prognostic markers for overall survival and recurrence-free survival in patients with IHCC. Conclusion Our data suggest, for the first time, that both the expression of NEP and DPP IV proteins may be upregulated in human IHCC tissues and the combined expression of NEP and DPP IV proteins may play important roles in progression and prognosis of patients with IHCC. PMID:24570591

  16. Prognostic Significance of Tag SNP rs1045411 in HMGB1 of the Aggressive Gastric Cancer in a Chinese Population

    PubMed Central

    He, Li; Zhao, Huadong; Wang, Nan; Ji, Gang; He, Xianli

    2016-01-01

    Compelling evidences have suggested that high mobility group box-1 (HMGB1) gene plays a crucial role in cancer development and progression. This study aimed to evaluate the effects of single nucleotide polymorphisms (SNPs) in HMGB1 gene on the survival of gastric cancer (GC) patients. Three tag SNPs from HMGB1 gene were selected and genotyped using Sequenom iPEX genotyping system in a cohort of 1030 GC patients (704 in training set, 326 in validation set). Multivariate Cox proportional hazard model and Kaplan-Meier Curve were used for prognosis analysis. AG/AA genotypes of SNP rs1045411 in HMGB1 gene were significantly associated with better overall survival (OS) in a set of 704 GC patients when compared with GG genotypes (HR = 0.77, 95% CI: 0.60–0.97, P = 0.032). This prognostic effect was verified in an independent validation set and pooled analysis (HR = 0.80, 95% CI: 0.62–0.99, P = 0.046; HR = 0.78, 95% CI: 0.55–0.98, P = 0.043, respectively). In stratified analysis, the protective effect of rs1045411 AG/AA genotypes was more prominent in patients with adverse strata, compared with patients with favorable strata. Furthermore, strong joint predictive effects on OS of GC patients were noted between rs1045411 genotypes and Lauren classification, differentiation, stage or adjuvant chemotherapy. Additionally, functional assay indicated a significant effect of rs1045411 on HMGB1 expression. Our results suggest that rs1045411 in HMGB1 is significantly associated with clinical outcomes of Chinese GC patients after surgery, especially in those with aggressive status, which warrants further validation in other ethnic populations. PMID:27116470

  17. Heterogeneous chromosome 12p deletion is an independent adverse prognostic factor and resistant to bortezomib-based therapy in multiple myeloma

    PubMed Central

    Li, Fei; Xu, Yan; Deng, Ping; Yang, Ye; Sui, Weiwei; Jin, Fengyan; Hao, Mu; Li, Zengjun; Zang, Meirong; Zhou, Dehui; Gu, Zhimin; Ru, Kun; Wang, Jianxiang; Cheng, Tao; Qiu, Lugui

    2015-01-01

    The deletion of 12p (del(12p)) has been described as a novel negative prognostic marker in multiple myeloma (MM) and has gained increasing attention in recent years. However, its impact on MM is still controversial. In this study, we comprehensively evaluated the clinical impact of 12p13 deletion using fluorescence in situ hybridization (FISH) on 275 newly diagnosed MM cases treated in a prospective, non-randomized clinical trial (BDH 2008/02). The results showed that deletion of 12p13 was detected in 10.5% of newly diagnosed cases and associated with multiple indicators for high tumor burden including ISS III, BM plasmacytosis larger than 50%, and renal lesion. Moreover, the cases with 12p13 deletion typically had higher incidence of del(17p), IGH translocation and t(4;14). Patients with del(12p) conferred significantly adverse prognosis for PFS and OS, even in patients subjected to bortezomib-based therapy. When adjusted to the established prognostic variables including del(13q), del(17p), t(4;14), amp(1q21), ISS stage and LDH, del(12p13) remained the powerful independent adverse factor for PFS (P = 0.007) and OS (P = 0.032). In addition, del(12p13) combined with high β2-MG, high LDH and bone lesion can further identify subpopulations with high-risk features. Our results strongly supported that del(12p13) can be used as a valuable prognostic marker in MM. PMID:25831238

  18. Independent Prognostic Value of Single and Multiple Non-Specific 12-Lead Electrocardiographic Findings for Long-Term Cardiovascular Outcomes: A Prospective Cohort Study

    PubMed Central

    Sawano, Mitsuaki; Kohsaka, Shun; Okamura, Tomonori; Inohara, Taku; Sugiyama, Daisuke; Shiraishi, Yasuyuki; Watanabe, Makoto; Nakamura, Yasuyuki; Higashiyama, Aya; Kadota, Aya; Okuda, Nagako; Murakami, Yoshitaka; Ohkubo, Takayoshi; Fujiyoshi, Akira; Miura, Katsuyuki; Okayama, Akira; Ueshima, Hirotsugu

    2016-01-01

    Aims The long-term prognostic effect of non-specific 12-lead electrocardiogram findings is unknown. We aimed to evaluate the cumulative prognostic impact of axial, structural, and repolarization categorical abnormalities on cardiovascular death, independent from traditional risk scoring systems such as the Framingham risk score and the NIPPON DATA80 risk chart. Methods and Results A total of 16,816 healthy men and women from two prospective, longitudinal cohort studies were evaluated. 3,794 (22.6%) individuals died during a median follow-up of 15 years (range, 2.0–24 years). Hazard ratios for cardiovascular death, all-cause death, coronary death and stroke death were calculated for the cumulative and independent axial, structural, and repolarization categorical abnormalities adjusted for the Framingham risk score and the NIPPON DATA80 risk chart. Individuals with two or more abnormal categories had a higher risk of cardiovascular death after adjustment for Framingham risk score (men: HR 4.27, 95%CI 3.35–5.45; women: HR 4.83, 95%CI 3.76–6.22) and NIPPON DATA80 risk chart (men: HR 2.39, 95%CI 1.87–3.07; women: HR 2.04, 95%CI 1.58–2.64). Conclusion Cumulative findings of axial, structural, and repolarization abnormalities are significant predictors of long-term cardiovascular death in asymptomatic, healthy individuals independent of traditional risk stratification systems. PMID:27362562

  19. Prognostic indicators in primary biliary cirrhosis: significance of revised IAHG (International Autoimmune Hepatitis Group) score

    PubMed Central

    Jung, Ho Eun; Jeong, Soung Won; Kim, Jin Nyoung; Jang, Hee Yoon; Cho, Yun Ju; Woo, Sung Ae; Lee, Sae Hwan; Kim, Sang Gyune; Cha, Sang-Woo; Kim, Young Seok; Cho, Young Deok; Kim, Hong Soo; Kim, Boo Sung

    2012-01-01

    Background/Aims Primary biliary cirrhosis (PBC) is a slowly progressing autoimmune disease of the liver that is characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Serum total bilirubin is one of the various prognostic factors that have been proposed. A recent study found that PBC with accompanying autoimmune hepatitis (AIH) carries a negative prognosis. This study examined the clinical characteristics of PBC and analyzed the factors that affect its prognosis. Methods Patients diagnosed with PBC between January 1998 and December 2010 based on clinical and histopathological findings were compiled and analyzed retrospectively. Results Among 27 patients, 24 (1 male and 23 females, ages 50.0±9.3 years) were followed up. The follow-up period was 8.6±0.9 years. Of the 24 patients, 9 patients progressed to liver cirrhosis (LC). Comparison between patients who did and did not progress to LC revealed statistically significant differences in the patients' serum total bilirubin (2.7±1.8 vs. 0.8±0.4, P=0.012), the Mayo risk score (5.1±0.7 vs. 3.9±0.6, P=0.001), the revised IAHG (International Autoimmune Hepatitis Group) score (9.2±2.3 vs. 5.4±3.0, P=0.004) and frequency of AIH overlap (5/9 [55.6%] vs. 0/15 [0%], P=0.001) at the time of diagnosis. Conclusions We propose that serum total bilirubin, the Mayo risk score, and the revised IAHG score at the time of diagnosis are helpful for predicting PBC prognosis. In particular, since all of the patients with accompanying AIH progressed to LC, the presence of overlap syndrome at the time of diagnosis is helpful for predicting PBC prognosis and providing an adequate treatment. PMID:23323253

  20. Prognostic Significance of Lymph Node Metastases and Ratio in Esophageal Cancer

    PubMed Central

    Wilson, Matthew; Rosato, Ernest L.; Chojnacki, Karen A.; Chervoneva, Inna; Kairys, John C.; Cohn, Herbert E.; Rosato, Francis E.; Berger, Adam C.

    2008-01-01

    Background The incidence of carcinoma of the distal esophagus and GE junction is rapidly increasing. A large single-center experience was reviewed to determine the impact of lymph node positivity and ratio on survival. Methods All patients undergoing esophagogastrectomy at Thomas Jefferson University Hospital between January 1994 and December 2004 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazard models, and survival curves estimated using the Kaplan-Meier method. Results Of 173 patients with invasive cancer, 123 (71%) underwent preoperative chemoradiation therapy (CRT). The largest number of patients (45%) had adenocarcinoma of the GE junction; 29% of patients had esophageal adenocarcinoma while 14% had squamous cell cancer of the esophagus. Perioperative mortality was 5.7%. Median overall survival (OS) of the entire group was 22 months and 5-year OS was 27%. The most significant prognostic factor for overall survival was the presence of positive LN (p=0.01). Additionally, patients with zero involved LN had a 5-year survival of 34%, while patients with 1–3 positive LN and >3 positive LN had 5-year survival of 27% and 9%, respectively (p=0.01). Finally, an increasing ratio of positive to examined LN was linearly associated with a worsening 5-year survival, (p=0.153). Conclusions Increasing number of positive LN in patients with esophageal cancer and increasing ratio of metastatic to examined LN portend a poor prognosis. These factors should play an important role in determining which patients receive adjuvant therapy. PMID:18028955

  1. Prognostic Significance of p16 Expression in Advanced Cervical Cancer Treated With Definitive Radiotherapy

    SciTech Connect

    Schwarz, Julie K.; Lewis, James S.; Pfeifer, John; Huettner, Phyllis; Grigsby, Perry

    2012-09-01

    Purpose: The purpose of this study was to evaluate the prognostic significance of p16 immunohistochemistry (IHC) in patients with advanced cervical cancer treated with radiation therapy. Materials and Methods: This was a retrospective study of 126 patients with International Federation of Gynecology and Obstetrics Stages Ib1-IVb cervical cancer treated with radiation. Concurrent cisplatin chemotherapy was given to 108 patients. A tissue microarray (TMA) was constructed from the paraffin-embedded diagnostic biopsy specimens. Immunoperoxidase staining was performed on the TMA and a p16 monoclonal antibody was utilized. IHC p16 extent was evaluated and scored in quartiles: 0 = no staining, 1 = 1-25% of cells staining, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100%. Results: The p16 IHC score was 4 in 115 cases, 3 in 1, 2 in 3 and 0 in 7. There was no relationship between p16 score and tumor histology. Patients with p16-negative tumors were older (mean age at diagnosis 65 vs. 52 years for p16-positive tumors; p = 0.01). The 5-year cause-specific survivals were 33% for p16-negative cases (score = 0) compared with 63% for p16-positive cases (scores 1, 2, 3 or 4; p = 0.07). The 5-year recurrence-free survivals were 34% for those who were p16-negative vs. 57% for those who were p16-positive (p = 0.09). In addition, patients with p16-positive tumors (score > 0) were more likely to be complete metabolic responders as assessed by the 3-month posttherapy 18 [F]-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomograph compared with patients with p16-negative tumors (p = 0.03). Conclusion: p16 expression is predictive of improved survival outcome after chemoradiation therapy for advanced-stage invasive cervical carcinoma. Further testing will be needed to evaluate p16-negative cervical tumors.

  2. MiR-378 is an independent prognostic factor and inhibits cell growth and invasion in colorectal cancer

    PubMed Central

    2014-01-01

    Background MicroRNAs(miRNAs) are small non-coding RNAs that participate in a variety of biologic processes, and dysregulation of miRNA is always associated with cancer development and progression. Aberrant expression of miR-378 has been found in some types of cancer. However, effects and potential mechanisms of miR-378 in colorectal cancer (CRC) have not been explored. Methods Quantitative RT-PCR was performed to evaluate miR-378 levels in CRC cell lines and 84 pairs of CRC cancer and normal adjacent mucosa. Kaplan–Meier and Cox proportional regression analyses were utilized to determine the association of miR-378 expression with survival of patients. MTT and invasion assays were used to determine the role of miR-378 in regulation of CRC cancer cell growth and invasion, respectively. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. Luciferase assay was performed to assess miR-378 binding to vimentin gene. Results In this study, we confirmed that miR-378 significantly down-regulated in CRC cancer tissues and cell lines. Moreover, patients with low miR-378 expression had significantly poorer overall survival, and miR-378 expression was an independent prognostic factor in CRC. Over-expression of miR-378 inhibited SW620 cell growth and invasion, and resulted in down-regulation of vimentin expression. However, miR-378 knock-down promoted these processes and enhanced the expression of vimentin. In addition, we further identified vimentin as the functional downstream target of miR-378 by directly targeting the 3′-UTR of vimentin. Conclusions In conclusion, miR-378 may function as a tumor suppressor and plays an important role in inhibiting tumor growth and invasion. Our present results implicate the potential effects of miR-378 on prognosis and treatment of CRC cancer. PMID:24555885

  3. Assessment of Copy Number Status of Chromosomes 6 and 11 by FISH Provides Independent Prognostic Information in Primary Melanoma

    PubMed Central

    North, Jeffrey P.; Vetto, John T.; Murali, Rajmohan; White, Kevin P.; White, Clifton R.; Bastian, Boris C.

    2014-01-01

    Melanoma incidence has been rising steadily for decades, while mortality rates have remained flat. This type of discordant pattern between incidence and mortality has been linked to diagnostic drift in cancers of the thyroid, breast, and prostate. Ancillary tests such as fluorescent in situ hybridization (FISH) are now being used to help differentiate melanomas from melanocytic nevi. Multicolor FISH has been shown to distinguish between these two with 86.7% sensitivity and 95.4% specificity. To assess the ability of FISH to differentiate melanomas with metastatic or lethal potential from those with an indolent disease course, we performed FISH with probes targeting 6p25, centromere 6, 6q23, and 11q13 on 144 primary melanomas with a minimal tumor thickness of 2 mm and compared the development of metastatic disease and melanoma-specific mortality as well as relapse-free and disease-specific survival between FISH-positive and negative cases. 82% of melanomas were positive by FISH according to previously defined criteria. The percentage was significantly higher (93%) in cases that developed systemic metastases (n=43) than in patients that did not (77%, n=101). FISH-positive primaries had a significantly increased risk of metastasis or melanoma-related death compared to FISH-negative cases (odds ratio 4.11, confidence interval (CI) 1.14-22.7 and 7.0, CI 1.03-300.4, respectively). FISH status remained an independent parameter when controlling for known prognostic factors. This data indicates that the group of melanomas diagnosed with routine histopathology that lack aberrations detected by FISH is enriched for melanomas with a more indolent disease course. This suggests that molecular techniques can assist in a more accurate identification of tumors with metastatic potential. PMID:21716079

  4. Prognostic Significance of Neuroendocrine Differentiation in Patients With Gleason Score 8-10 Prostate Cancer Treated With Primary Radiotherapy

    SciTech Connect

    Krauss, Daniel J.; Hayek, Sylvia; Amin, Mitual; Ye Hong; Kestin, Larry L.; Zadora, Steven; Vicini, Frank A.; Cotant, Matthew; Brabbins, Donald S.; Ghilezan, Michel I.; Gustafson, Gary S.; Martinez, Alvaro A.

    2011-11-01

    Purpose: To determine the prognostic significance of neuroendocrine differentiation (NED) in Gleason score 8-10 prostate cancer treated with primary radiotherapy (RT). Methods and Materials: Chromogranin A (CgA) staining was performed and overseen by a single pathologist on core biopsies from 176 patients from the William Beaumont prostate cancer database. A total of 143 had evaluable biopsy material. Staining was quantified as 0%, <1%, 1-10%, or >10% of tumor cells. Patients received external beam RT alone or together with high-dose-rate brachytherapy. Cox regression and Kaplan-Meier estimates determined if the presence/frequency of neuroendocrine cells correlated with clinical endpoints. Results: Median follow-up was 5.5 years. Forty patients (28%) had at least focal positive CgA staining (<1% n = 21, 1-10% n = 11, >10% n = 8). No significant differences existed between patients with or without staining in terms of age, pretreatment prostate-specific antigen, tumor stage, hormone therapy administration, % biopsy core involvement, mean Gleason score, or RT dose/modality. CgA staining concentration independently predicted for biochemical and clinical failure, distant metastases (DM), and cause-specific survival (CSS). For patients with <1% vs. >1% staining, 10-year DM rates were 13.4% vs. 55.3%, respectively (p = 0.001), and CSS was 91.7% vs. 58.9% (p < 0.001). As a continuous variable, increasing CgA staining concentration predicted for inferior rates of DM, CSS, biochemical control, and any clinical failure. No differences in outcomes were appreciated for patients with 0% vs. <1% NED. Conclusions: For Gleason score 8-10 prostate cancer, >1% NED is associated with inferior clinical outcomes for patients treated with radiotherapy. This relates most directly to an increase in distant disease failure.

  5. Prognostic Significance of Human Apurinic/Apyrimidinic Endonuclease (APE/Ref-1) Expression in Rectal Cancer Treated With Preoperative Radiochemotherapy

    SciTech Connect

    Kim, Jun-Sang; Kim, Jin-Man; Liang, Zhe Long; Jang, Ji Young; Kim, Sup; Huh, Gil Ja; Kim, Ki-Hwan; Cho, Moon-June

    2012-01-01

    Purpose: Human apurinic endonuclease/redox factor 1 (APE/Ref-1) mediates repair of radiation-induced DNA lesions and regulates transcription via redox-based activation. We investigated the predictive and prognostic significance of APE/Ref-1 expression in pretreatment biopsy specimens in locally advanced rectal cancer (LARC) (cT3-T4 or N+). Methods and Materials: APE/Ref-1 expression was analyzed by immunohistochemistry in pretreatment biopsy specimens obtained from 83 patients with LARC. Patients received preoperative radiotherapy of 50.4 Gy in 28 fractions, combined with oral capecitabine and leucovorin chemotherapy, followed by curative surgery. The prognostic significance of various clinicopathologic characteristics, including APE/Ref-1 protein expression, was evaluated. Results: APE/Ref-1 was expressed in 97% of patient samples. Exclusive APE/Ref-1 nuclear staining was observed in 49 of 83 samples (59%), and mixed nuclear and cytoplasmic staining was observed in 31 samples (37%). APE/Ref-1 nuclear expression levels were low in 49 patients (59%) and high in 34 patients (41%). The level of APE/Ref-1 nuclear expression was not a prognostic factor for overall and disease-free survival. Cytoplasmic expression of APE/Ref-1 was a borderline-significant predictive factor for pathologic tumor response (p = 0.08) and a significant prognostic factor for disease-free survival, as shown by univariate analysis (p = 0.037). Multivariate analysis confirmed that cytoplasmic localization of APE/Ref-1 is a significant predictor of disease-free survival (hazard ratio, 0.45; p = 0.046). Conclusions: APE/Ref-1 was expressed in a majority of pretreatment biopsy specimens from patients with LARC. The level of APE/Ref-1 nuclear expression was not a significant predictive and prognostic factor; however, cytoplasmic localization of the protein was negatively associated with disease-free survival. These results indicate that cytoplasmic expression of APE/Ref-1 represents an adverse

  6. Prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet in patients with gastric carcinoma: a retrospective cohort study

    PubMed Central

    Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Yang, Kun; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2015-01-01

    Nutritional and immune status is important to the prognosis of patients with gastric carcinoma (GC). Here, we evaluated the prognostic significance of the combination of preoperative hemoglobin, albumin, lymphocyte and platelet (HALP) in patients with GC. From January 2005 to December 2011, 1332 patients with GC who underwent gastrectomy were randomly divided into the training (n = 888) and the validation sets (n = 444) by X-tile according to the sample size ratio 2:1. The cut-point of HALP was 56.8 and the patients were subsequently subdivided into HALP < 56.8 and HALP ≥ 56.8 groups in both two sets. Multivariate analysis revealed that gender (p < 0.001, p < 0.001), tumor size (p = 0.003, p = 0.035) and T stage (p < 0.001, p = 0.044) were independently related to HALP both in the training and the validation sets. Kaplan-Meier (p < 0.001, p = 0.003) and Cox regression (p = 0.043, p = 0.042) showed that the prognosis of HALP ≥ 56.8 group was significantly better than that of HALP < 56.8 group both in two sets (p < 0.001, p < 0.001). Nomograms of these two sets based on HALP was more accurate in prognostic prediction than TNM stage alone. Our findings suggested that HALP was closely associated with clinicopathological features and was an independent prognostic factor in GC patients. Nomogram based on HALP could accurately predict the prognosis of GC patients. PMID:26497995

  7. Diagnostic and prognostic significance of serum apolipoprotein C-I in triple-negative breast cancer based on mass spectrometry.

    PubMed

    Song, Dongjian; Yue, Lifang; Zhang, Junjie; Ma, Shanshan; Zhao, Wei; Guo, Fei; Fan, Yingzhong; Yang, Heying; Liu, Qiuliang; Zhang, Da; Xia, Ziqiang; Qin, Pan; Jia, Jia; Yue, Ming; Yu, Jiekai; Zheng, Shu; Yang, Fuquan; Wang, Jiaxiang

    2016-06-01

    Women with triple-negative breast cancer (TNBC) have poor prognosis because of the aggressive nature of the tumor, delayed diagnosis and non-specific symptoms in the early stages. Identification of novel specific TNBC serum biomarkers for screening and therapeutic purposes therefore remains an urgent clinical requirement.We obtained serum samples from a total of 380 recruited individuals split into mining and testing sets, with the aim of screening for reliable protein biomarkers from TNBC and non-TNBC (NTNBC) sera. Samples were assessed using mass spectrometry, followed by receiver operating characteristic (ROC), survival and hazard function curve as well as multivariate Cox regression analyses to ascertain the potential of the protein constituents as diagnostic and prognostic biomarkers for TNBC.We identified upregulated apolipoprotein C-I (apoC-I) with a validated positive effect on TNBC tumorigenesis, with confirmation in an independent test set and minimization of systematic bias by pre-analytical parameters. The apoC-I protein had superior diagnostic ability in distinguishing between TNBC and NTNBC cases. Moreover, the protein presented a more robust potential prognostic factor for TNBC than NTNBC. The apoC-I protein identified in this study presents an effective novel diagnostic and prognostic biomarker for TNBC, indicating that measurement of the peak intensity at 7785 Da in serum samples could facilitate improved early detection and estimation of postoperative survival prognosis for TNBC. PMID:27260686

  8. Plasma cells in primary melanoma. Prognostic significance and possible role of IgA.

    PubMed

    Bosisio, Francesca M; Wilmott, James S; Volders, Nathalie; Mercier, Marjorie; Wouters, Jasper; Stas, Marguerite; Blokx, Willeke Am; Massi, Daniela; Thompson, John F; Scolyer, Richard A; van Baren, Nicolas; van den Oord, Joost J

    2016-04-01

    Melanoma is not only one of the most immunogenic cancers but also one of the most effective cancers at subverting host immunity. The role of T lymphocytes in tumor immunity has been extensively studied in melanoma, whereas less is known about the importance of B lymphocytes. The effects of plasma cells (PCs), in particular, are still obscure. The aim of this study was to characterize pathological features and clinical outcome of primary cutaneous melanomas associated with PCs. Moreover, we investigated the origins of the melanoma-associated PCs. Finally, we studied the outcome of patients with primary melanomas with PCs. We reviewed 710 melanomas to correlate the presence of PCs with histological prognostic markers. Immunohistochemistry for CD138 and heavy and light chains was performed in primary melanomas (PM) and in loco-regional lymph nodes (LN), both metastatic and not metastatic. In three PM and nine LN with frozen material, VDJ-rearrangement was analyzed by Gene Scan Analysis. Survival analysis was performed on a group of 85 primary melanomas >2 mm in thickness. Forty-one cases (3.7%) showed clusters/sheets of PCs. PC-rich melanomas occurred at an older age and were thicker, more often ulcerated and more mitotically active (P<0.05). PCs were polyclonal and often expressed IgA in addition to IgG. In LN, clusters/sheets of IgA+ PCs were found both in the sinuses and subcapsular areas. Analysis of VDJ-rearrangements showed the IgA to be oligoclonal. Melanomas with clusters/sheets of PCs had a significantly worse survival compared with melanomas without PCs while, interestingly, melanomas with sparse PCs were associated with a better clinical outcome (P=0.002). In conclusion, melanomas with sheets/clusters of PCs are associated with worse prognosis. IgG and IgA are the isotypes predominantly produced by these PCs. IgA oligoclonality suggests an antigen-driven response that facilitates melanoma progression by a hitherto unknown mechanism. PMID:26867783

  9. Prognostic significance of neoplastic cell proliferation parameters in human haematological malignancies.

    PubMed

    Kotelnikov, V M

    1990-01-01

    High percentage of neoplastic cells in S, G2 and M phases of cell cycle is unfavourable prognostic sign in human haematological malignancies. In chronic leukaemias (CML and CLL) it is true for peripheral blood leukaemic cells, in non-Hodgkin lymphomas--for lymph node cells, in multiple myeloma--for bone marrow plasma cells. In acute leukaemia results are controversial: some authors found a correlation between proliferation parameters of bone marrow blast cells while others did not. These parameters correlate positively with the rate of complete remission and negatively with its duration. It is concluded that proliferation parameters of neoplastic cells may be used for individual prognosis in patients with haematological tumours especially in combination with other biological and clinical prognostic markers. PMID:1703108

  10. An improved image analysis method for cell counting lends credibility to the prognostic significance of T cells in colorectal cancer.

    PubMed

    Väyrynen, Juha P; Vornanen, Juha O; Sajanti, Sara; Böhm, Jan P; Tuomisto, Anne; Mäkinen, Markus J

    2012-05-01

    Numerous immunohistochemically detectable proteins, such as immune cell surface (CD) proteins, vascular endothelial growth factor, and matrix metalloproteinases, have been proposed as potential prognostic markers in colorectal cancer (CRC) and other malignancies. However, the lack of reproducibility has been a major problem in validating the clinical use of such markers, and this has been attributed to insufficiently robust methods used in immunohistochemical staining or its assessment. In this study, we assessed how computer-assisted image analysis might contribute to the reliable assessment of positive area percentage and immune cell density in CRC specimens, and subsequently, we applied the computer-assisted cell counting method in assessing the prognostic value of T cell infiltration in CRC. The computer-assisted analysis methods were based on separating hematoxylin and diaminobenzidine color layers and then applying a brightness threshold using open source image analysis software ImageJ. We found that computer-based analysis results in a more reproducible assessment of the immune positive area percentage than visual semiquantitative estimation. Computer-assisted immune cell counting was rapid to perform and accurate (Pearson r > 0.96 with exact manual cell counts). Moreover, the computer-assisted determination of peritumoral and stromal T cell density had independent prognostic value. Our results suggest that computer-assisted image analysis, utilizing freely available image analysis software, provides a valuable alternative to semiquantitative assessment of immunohistochemical results in cancer research, as well as in clinical practice. The advantages of using computer-assisted analysis include objectivity, accuracy, reproducibility, and time efficiency. This study supports the prognostic value of assessing T cell infiltration in CRC. PMID:22527018

  11. Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma.

    PubMed

    Hillengass, Jens; Ritsch, Judith; Merz, Maximilian; Wagner, Barbara; Kunz, Christina; Hielscher, Thomas; Laue, Hendrik; Bäuerle, Tobias; Zechmann, Christian M; Ho, Anthony D; Schlemmer, Heinz-Peter; Goldschmidt, Hartmut; Moehler, Thomas M; Delorme, Stefan

    2016-07-01

    This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0·89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS. PMID:26991959

  12. Ki67/SATB1 ratio is an independent prognostic factor of overall survival in patients with early hormone receptor-positive invasive ductal breast carcinoma

    PubMed Central

    Laurinavicius, Arvydas; Green, Andrew R.; Laurinaviciene, Aida; Smailyte, Giedre; Ostapenko, Valerijus; Meskauskas, Raimundas; Ellis, Ian O.

    2015-01-01

    Biological diversity of breast cancer presents challenges for personalized therapy and necessitates multiparametric approaches to understand and manage the disease. Multiple protein biomarkers tested by immunohistochemistry (IHC), followed by digital image analysis and multivariate statistics of the data, have been shown to be effective in exploring latent profiles of tumor tissue immunophenotype. In this study, based on tissue microarrays of 107 patients with hormone receptor (HR) positive invasive ductal breast carcinoma, we investigated the prognostic value of the integrated immunophenotype to predict overall survival (OS) of the patients. A set of 10 IHC markers (ER, PR, HER2, Ki67, AR, BCL2, HIF-1α, SATB1, p53, and p16) was used. The main factor of the variance was characterized by opposite loadings of ER/PR/AR/BCL2 and Ki67/HIF-1α; it was associated with histological grade but did not predict OS. The second factor was driven by SATB1 expression along with moderate positive HIF-1α and weak negative Ki67 loadings. Importantly, this factor did not correlate with any clinicopathologic parameters, but was an independent predictor of better OS. Ki67 and SATB1 did not reach statistical significance as single predictors; however, high Ki67/SATB1 ratio was an independent predictor of worse OS. In addition, our data indicate potential double prognostic meaning of HIF-1α expression in breast cancer and necessitate focused studies, taking into account the immunophenotype interactions and tissue heterogeneity aspects. PMID:26512778

  13. Prognostic significance of ASXL1, JAK2V617F mutations and JAK2V617F allele burden in Philadelphia-negative myeloproliferative neoplasms

    PubMed Central

    Yonal-Hindilerden, Ipek; Daglar-Aday, Aynur; Akadam-Teker, Basak; Yilmaz, Ceylan; Nalcaci, Meliha; Yavuz, Akif Selim; Sargin, Deniz

    2015-01-01

    Background Despite insights into the genetic basis of Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs), a significant proportion of essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients present with no known MPN disease alleles. There were no previous studies investigating the impact of ASXL1 mutations in Ph-negative MPNs in Turkey. In the current study, we investigated the prognostic significance of ASXL1 mutations in Turkish MPN patients. We also aimed to determine the prognostic significance of JAK2V617F allele burden and the relationship of JAK2V617F mutation with ASXL1 mutations in Ph-negative MPNs. Methods About 184 patients from a single center diagnosed with Ph-negative MPNs were screened for ASXL1, JAK2V617F mutations, and JAK2V617F allele burden: 107 ET and 77 PMF. Results A total of 29 ASXL1 mutations were detected in 24.7% of PMF and 8.4% of ET patients. ASXL1-mutated ET patients showed a trend toward an increase in the incidence of cerebrovascular events and higher total leukocyte counts. ASXL1-mutation in PMF was associated with older age and a higher prevalence of bleeding complications. In univariate analysis, overall survival (OS) was significantly reduced in ASXL1-mutated PMF patients. In multivariate analysis, Dynamic International Prognostic Scoring System-plus high-risk category and ASXL1 mutation status were independently associated with shorter survival in PMF. In PMF, mutational status and allele burden of JAK2V617F showed no difference in terms of OS and leukemia-free survival. Conclusion We conclude that ASXL1 mutations are molecular predictors of short OS in PMF. PMID:26082670

  14. Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Patients with Sepsis: A Prospective Observational Study

    PubMed Central

    Liu, Xuan; Shen, Yong; Wang, Hairong; Ge, Qinmin; Fei, Aihua; Pan, Shuming

    2016-01-01

    Background. The neutrophil-to-lymphocyte ratio (NLR) is an easily accessible biological marker that has been reported to represent disease severity. The aim of this study is to investigate the association between NLR and mortality in patients with sepsis. Methods. A total of 333 consecutive adult patients with sepsis were screened for eligibility in this prospective, observational study cohort. Severity scores and leukocyte counts were prospectively recorded upon entry to the intensive care unit (ICU). Receiver operating characteristic (ROC) curves and binary logistic regression models were used to assess the performance of NLR in predicting unfavorable outcome. Correlations between variables and disease severity were analyzed through Spearman correlation tests. Results. Median NLR levels were significantly higher in patients who died than in survivors. NLR had a modest power for predicting poor outcome as suggested by area under the curve (AUC) of 0.695 ± 0.036. Multivariate linear regression indicated that increased NLR levels were related to unfavorable outcome independently of the effect of possible confounders. Spearman correlation tests showed that there was a positive correlation between NLR levels and disease severity. Conclusions. Increased NLR levels were independently associated with unfavorable clinical prognosis in patients with sepsis. Further investigation is required to increase understanding of the pathophysiology of this relationship. PMID:27110067

  15. Prognostic significance of ubiquinol-cytochrome c reductase hinge protein expression in patients with clear cell renal cell carcinoma

    PubMed Central

    Liu, Wei-Si; Liu, Yi-Dong; Fu, Qiang; Zhang, Wei-Juan; Xu, Le; Chang, Yuan; Xu, Jie-Jie

    2016-01-01

    Ubiquinol-cytochrome c reductase hinge protein (UQCRH), as a connecter between cytochrome c1 with cytochrome c in complex III of respiratory chain, is top-ranked hypermethylated gene in clear cell renal cell carcinoma (ccRCC). This study aims to evaluate the impact of UQCRH on recurrence and survival of 424 ccRCC patients enrolled retrospectively from a single institution after surgical resection using immunohistochemistry method. UQCRH was specifically downregulated in ccRCC, compared with papillary and chromophobe RCC. Moreover, patients with low UQCRH were prone to possess high T stage and TNM stage and associated with poor survival and early recurrence. UQCRH remained an independent favorable prognosticator for OS (Hazard rate [HR]: 0.510, 95% CI: 0.328-0.795, p=0.003) and RFS (HR: 0.506, 95% CI: 0.334-0.767, p=0.001) adjusting with other well-established factors using backward Cox model. Furthermore, in stratified subgroups, patients with low UQCRH had an increased risk of recurrence (HR: 0.452, 95% CI: 0.261-0.783, p=0.005) and mortality (HR: 0.386, 95% CI: 0.205-0.726, p=0.003) in subgroup of early TNM stage. Taken together, UQCRH is a potential independent favorable prognostic factor for recurrence and survival of patients with ccRCC after nephrectomy. PMID:27186431

  16. Prognostic significance of 5T4 oncofetal antigen expression in colorectal carcinoma.

    PubMed

    Starzynska, T; Marsh, P J; Schofield, P F; Roberts, S A; Myers, K A; Stern, P L

    1994-05-01

    The 5T4 oncofetal antigen is a 72 kDa glycoprotein defined by a monoclonal antibody raised against human placental trophoblast and is expressed in many different carcinomas but detected only at low levels in some normal epithelia. Immunohistochemical analysis of the patterns of expression in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumour cells and metastatic spread. The 5T4 antigen phenotype of 72 colorectal cancers has been compared with the clinical outcome of the patients in order to assess its relationship with prognosis. Forty per cent of tumours were 5T4 positive; the remainder were either unlabelled or exhibited stroma-associated labelling only. There was a significant correlation between 5T4 expression in the malignant cells and unfavourable course of disease (P < 0.001). The 5 year survival with 5T4-positive tumours was 22% compared with 75% for patients with 5T4-negative tumours; median survival was 24 versus > 90 months respectively. Stratified analysis showed that 5T4 antigen tumour positivity was acting independently of each of stage, site of tumour, age or sex. There were significant differences in survival for patients with Dukes' B and C stage carcinomas (P = 0.001 and P = 0.034). The results suggest that in colorectal cancer immunohistochemical assessment of 5T4 expression may be useful in identifying patients at high risk for tumour recurrence and for whom additional treatment strategies might be most appropriate. PMID:8180020

  17. Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy

    PubMed Central

    Hosokawa, Takanori; Kurosaki, Masayuki; Tsuchiya, Kaoru; Matsuda, Shuya; Muraoka, Masaru; Suzuki, Yuichiro; Tamaki, Nobuharu; Yasui, Yutaka; Nakata, Toru; Nishimura, Takashi; Suzuki, Shoko; Ueda, Ken; Nakanishi, Hiroyuki; Itakura, Jun; Takahashi, Yuka; Izumi, Namiki

    2013-01-01

    AIM: To evaluate whether metabolic factors are related to distant recurrence of hepatocellular carcinoma (HCC) and survival after curative treatment. METHODS: This retrospective study included 344 patients whose HCC was treated curatively by radiofrequency ablation (RFA) therapy. The mean age was 67.6 years and the mean observation period was 4.04 years. The etiological background of liver disease was hepatitis B virus infection in 30, hepatitis C virus infection in 278, excessive alcohol drinking in 9, and other in 27 patients. The Child-Pugh classification grade was A (n = 307) or B (n = 37). The number of HCC nodules was one in 260, two in 61, and three in 23 patients. For surveillance of HCC recurrence after curative therapy with RFA, patients were radiologically evaluated every 3 mo. Factors associated with distant recurrence of HCC or survival were studied. RESULTS: Inadequate maintenance of blood glucose in diabetic patients was associated with higher incidence of distant recurrence. The 1-, 2-, and 3-year recurrence rates were significantly higher in diabetic patients with inadequate maintenance of blood glucose compared with the others: 50.6% vs 26.8%, 83.5% vs 54.4%, and 93.8% vs 73.0%, respectively (P = 0.0001). Inadequate maintenance of blood glucose was an independent predictor of distant recurrence [adjusted relative risk 1.97 (95%CI, 1.33-2.91), (P = 0.0007)] after adjustment for other risk factors, such as number of HCC nodules [2.03 (95%CI, 1.51-2.73), P < 0.0001] and initial level of serum alpha fetoprotein (AFP) [1.43 (95%CI, 1.04-1.97), P = 0.028]. Obesity was not an independent predictor of recurrence. The incidence of distant recurrence did not differ between diabetic patients with adequate maintenance of blood glucose and non-diabetic patients. Among 232 patients who had HCC recurrence, 138 had a second recurrence. The 1-, 2-, and 3-year rates of second recurrence were significantly higher in diabetic patients with inadequate maintenance of

  18. Expression and prognostic significance of a new tumor metastasis suppressor gene LASS2 in human bladder carcinoma.

    PubMed

    Wang, Haifeng; Wang, Jiansong; Zuo, Yigang; Ding, Mingxia; Yan, Ruping; Yang, Delin; Ke, Changxin

    2012-09-01

    The LASS2 gene has been identified as a new tumor metastasis suppressor gene and has been seen to correlate with the degree of invasion and recurrence in carcinomas of prostate, breast, liver, ovarian, and pancreas. However, expression and prognostic significance of LASS2 in human bladder carcinoma are largely unknown. In this study, the protein expression of LASS2 in 80 patients with different stages was detected by immunohistochemical staining. The prognostic value of LASS2 in bladder cancers can also be assessed by a long-term follow-up investigation. The mRNA expression level of the LASS2 gene was examined using real-time quantitative PCR (qPCR) in human bladder carcinoma and paired non-tumor bladder tissues, which were obtained from 30 patients who underwent total cystectomy. We found that patients with LASS2-negative bladder cancer were linked to poor clinical prognosis. The expression of LASS2 mRNA was significantly correlated with clinical stage (P < 0.001), depth of tumor invasion (P < 0.001), and recurrence (P < 0.001). Thus, LASS2 expression may be correlated with the development and progression of human bladder carcinoma and may be a prognostic indicator for this carcinoma. PMID:21755371

  19. Clinicopathological and prognostic significance of RECQL5 helicase expression in breast cancers.

    PubMed

    Arora, Arvind; Abdel-Fatah, Tarek M A; Agarwal, Devika; Doherty, Rachel; Croteau, Deborah L; Moseley, Paul M; Hameed, Khalid; Green, Andrew; Aleskandarany, Mohammed A; Rakha, Emad A; Patterson, Karl; Ball, Graham; Chan, Stephen Y T; Ellis, Ian O; Bohr, Vilhelm A; Bryant, Helen E; Madhusudan, Srinivasan

    2016-01-01

    RECQL5 is a member of the RecQ family of DNA helicases and has key roles in homologous recombination, base excision repair, replication and transcription. The clinicopathological significance of RECQL5 expression in breast cancer is unknown. In this study, we have evaluated RECQL5 mRNA expression in 1977 breast cancers, and RECQL5 protein level in 1902 breast cancers [Nottingham Tenovus series (n = 1650) and ER- cohort (n = 252)]. Expression levels were correlated to aggressive phenotypes and survival outcomes. High RECQL5 mRNA expression was significantly associated with high histological grade (P = 0.007), HER2 overexpression (P = 0.032), ER+/HER2-/high proliferation genefu subtype (P < 0.0001), integrative molecular clusters (intClust 1and 9) (P < 0.0001) and poor survival (P < 0.0001). In subgroup analysis, high RECQL5 mRNA level remains significantly associated with poor BCSS in ER+ cohort (P < 0.0001) but not in ER- cohort (P = 0.116). At the protein level, in tumours with low RAD51, high RECQL5 level was significantly associated with high histological grade (P < 0.0001), higher mitotic index (P = 0.008), dedifferentiation (P = 0.025), pleomorphism (P = 0.027) and poor survival (P = 0.003). In subgroup analysis, high RECQL5/low RAD51 remains significantly associated with poor BCSS in ER+ cohort (P = 0.010), but not in ER- cohort (P = 0.628). In multivariate analysis, high RECQL5 mRNA and high RECQL5/low RAD51 nuclear protein coexpression independently influenced survival (P = 0.022) in whole cohort and in the ER+ subgroup. Preclinically, we show that exogenous expression of RECQL5 in MCF10A cells can drive proliferation supporting an oncogenic function for RECQL5 in breast cancer. We conclude that RECQL5 is a promising biomarker in breast cancer. PMID:26586793

  20. Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers: A Meta-Analysis.

    PubMed

    Xu, Feng; Liu, Fuquan; Zhao, Hongwei; An, Guangyu; Feng, Guosheng

    2015-12-01

    Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients' survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76-2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58-2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75-2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05-3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41-2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46-2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42-4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30-4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46-3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40-5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95% CIREM: 1.06-2.27; PREM = 0

  1. Prognostic significance of neutrophil-to-lymphocyte ratio in rectal cancer: a meta-analysis

    PubMed Central

    Dong, Yi-wei; Shi, Yan-qiang; He, Li-wen; Su, Pei-zhu

    2016-01-01

    Background Inflammatory responses play decisive roles in tumor development, immune surveillance, and responses to therapy. High neutrophil-to-lymphocyte ratio (NLR), as an inflammation index, has been reported to be a predictor for poor prognosis of various cancers. The purpose of this meta-analysis was to evaluate the prognostic value of NLR in patients with rectal cancer. Methods A comprehensive search of the literature was conducted through PubMed and EMBASE. Pooled hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the association between NLR and three outcomes: overall survival, disease-free survival, and recurrence-free survival. Results Seven cohorts involving 959 patients were included in this meta-analysis. Our pooled results demonstrated that elevated NLR was associated with poor overall survival (HR: 13.41, 95% CI: 4.90–36.72), disease-free survival (HR: 4.37, 95% CI: 2.33–8.19), and recurrence-free survival (HR: 3.64, 95% CI: 1.88–7.05). Conclusion An elevated NLR is a valuable and easily available prognostic marker for rectal cancer. It is associated with unfavorable overall survival, disease-free survival, and recurrence-free survival. NLR could be a useful candidate factor for making treatment decisions for individual patients with rectal cancer. PMID:27307753

  2. Sex differences in the prognostic significance of KRAS codons 12 and 13, and BRAF mutations in colorectal cancer: a cohort study

    PubMed Central

    2013-01-01

    Background Activating KRAS and BRAF mutations predict unresponsiveness to EGFR-targeting therapies in colorectal cancer (CRC), but their prognostic value needs further validation. In this study, we investigated the impact of KRAS codons 12 and 13, and BRAF mutations on survival from CRC, overall and stratified by sex, in a large prospective cohort study. Methods KRAS codons 12 and 13, and BRAF mutations were analysed by pyrosequencing of tumours from 525 and 524 incident CRC cases in The Malmö Diet and Cancer Study. Associations with cancer-specific survival (CSS) were explored by Cox proportional hazards regression, unadjusted and adjusted for age, TNM stage, differentiation grade, vascular invasion and microsatellite instability (MSI) status. Results KRAS and BRAF mutations were mutually exclusive. KRAS mutations were found in 191/ 525 (36.4%) cases, 82.2% of these mutations were in codon 12, 17.3% were in codon 13, and 0.5% cases had mutations in both codons. BRAF mutations were found in 78/524 (14.9%) cases. Overall, mutation in KRAS codon 13, but not codon 12, was associated with a significantly reduced CSS in unadjusted, but not in adjusted analysis, and BRAF mutation did not significantly affect survival. However, in microsatellite stable (MSS), but not in MSI tumours, an adverse prognostic impact of BRAF mutation was observed in unadjusted, but not in adjusted analysis. While KRAS mutation status was not significantly associated with sex, BRAF mutations were more common in women. BRAF mutation was not prognostic in women; but in men, BRAF mutation was associated with a significantly reduced CSS in overall adjusted analysis (HR = 3.50; 95% CI = 1.41–8.70), but not in unadjusted analysis. In men with MSS tumours, BRAF mutation was an independent factor of poor prognosis (HR = 4.91; 95% CI = 1.99–12.12). KRAS codon 13 mutation was associated with a significantly reduced CSS in women, but not in men in unadjusted, but not in adjusted analysis. Conclusions

  3. Gene expression of INPP5F as an independent prognostic marker in fludarabine-based therapy of chronic lymphocytic leukemia

    PubMed Central

    Palermo, G; Maisel, D; Barrett, M; Smith, H; Duchateau-Nguyen, G; Nguyen, T; Yeh, R-F; Dufour, A; Robak, T; Dornan, D; Weisser, M

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Various disease-related and patient-related factors have been shown to influence the course of the disease. The aim of this study was to identify novel biomarkers of significant clinical relevance. Pretreatment CD19-separated lymphocytes (n=237; discovery set) and peripheral blood mononuclear cells (n=92; validation set) from the REACH trial, a randomized phase III trial in relapsed CLL comparing rituximab plus fludarabine plus cyclophosphamide with fludarabine plus cyclophosphamide alone, underwent gene expression profiling. By using Cox regression survival analysis on the discovery set, we identified inositol polyphosphate-5-phosphatase F (INPP5F) as a prognostic factor for progression-free survival (P<0.001; hazard ratio (HR), 1.63; 95% confidence interval (CI), 1.35–1.98) and overall survival (P<0.001; HR, 1.47; 95% CI, 1.18–1.84), regardless of adjusting for known prognostic factors. These findings were confirmed on the validation set, suggesting that INPP5F may serve as a novel, easy-to-assess future prognostic biomarker for fludarabine-based therapy in CLL. PMID:26430724

  4. The Overexpression of FEN1 and RAD54B May Act as Independent Prognostic Factors of Lung Adenocarcinoma

    PubMed Central

    Hwang, Jau-Chung; Sung, Wen-Wei; Tu, Hung-Pin; Hsieh, Kun-Chou; Yeh, Chung-Min; Chen, Chih-Jung; Tai, Hui-Chun; Hsu, Chao-Tien; Shieh, Grace S.; Chang, Jan-Gowth; Yeh, Kun-Tu; Liu, Ta-Chih

    2015-01-01

    Synthetic lethality arises when a combination of mutations in two or more genes leads to cell death. However, the prognostic role of concordant overexpression of synthetic lethality genes in protein level rather than a combination of mutations is not clear. In this study, we explore the prognostic role of combined overexpression of paired genes in lung adenocarcinoma. We used immunohistochemical staining to investigate 24 paired genes in 93 lung adenocarcinoma patients and Kaplan-Meier analysis and Cox proportional hazards models to evaluate their prognostic roles. Among 24 paired genes, only FEN1 (Flap endonuclease 1) and RAD54B (RAD54 homolog B) were overexpressed in lung adenocarcinoma patients with poor prognosis. Patients with expression of both FEN1 and RAD54B were prone to have advanced nodal involvement and significantly poor prognosis (HR = 2.35, P = 0.0230). These results suggest that intensive follow up and targeted therapy might improve clinical outcome for patients who show expression of both FEN1 and RAD54B. PMID:26431531

  5. Prognostic significance and optimal cutoff of age in medullary thyroid cancer

    PubMed Central

    Wang, Yu-long; Li, Duan-shu; Wang, Yu; Huang, Cai-ping; Ji, Qing-hai

    2016-01-01

    Age has been found to correlate with the prognosis for medullary thyroid cancer (MTC). This study was conducted to investigate whether age can predict long-term unfavorable prognosis and evaluate its predictive accuracy associated with TNM staging, using data of patients diagnosed with MTC between 2000 and 2010 from Surveillance, Epidemiology and End Results database. The relationship between the patients’ age at diagnosis and cancer-specific survival (CSS) was evaluated using multivariate Cox regression analysis. Age stratifications were combined into a nomogram model to predict the CSS of MTC. The X-tile program determined 49 and 69 as optimal age cutoff values for CSS. On multivariate analysis, independent factors for survival were age (50–69 years, HR 2.853, 95% CI 1.631–4.991; ≥70 years, HR 5.804, 95% CI 2.91–11.555), race (white, HR 0.344, 95% CI 0.188–0.630), T (T3/4, HR 3.931, 95% CI 2.093–7.381), N (N1a, HR 3.269, 95% CI 1.386–7.710) and M (M1, HR 3.998, 95% CI 2.419–6.606). The C-index for CSS prediction with TNM, age (cutoff of 45)/sex/race/TNM and age (cutoff of 49 and 69)/sex/race/TNM were 0.832 (95% CI 0.763–0.901), 0.863 (95% CI 0.799–0.928), and 0.876 (95% CI 0.817–0.935), respectively. Subgroup multivariate analyses also showed that age significantly increased the risk for CSS in females, non-Hispanic white patients, and those with stage IV MTC. In conclusion, CSS was independently associated with ages between 49 and 69 years, which might be applied for risk stratification in MTC patients. PMID:26910117

  6. Prognostic significance of the combined score of endothelial expression of nucleolin and CD31 in surgically resected non-small cell lung cancer.

    PubMed

    Zhao, Hongyun; Huang, Yan; Xue, Cong; Chen, Yang; Hou, Xue; Guo, Ying; Zhao, Liping; Hu, Zhi huang; Huang, Yujie; Luo, Yongzhang; Zhang, Li

    2013-01-01

    Nucleolin is implicated to play a role in angiogenesis, a vital process in tumor growth and metastasis. However, the presence and clinical relevance of nucleolin in human non small cell lung cancer (NSCLC) remains largely unknown. In this study, we explored the expression and prognostic implication of nucleolin in surgically resected NSCLC patients. A cohort of 146 NSCLC patients who underwent surgical resection was selected for tissue microarray. In this tissue microarray, nucleolin expression was measured by immunofluorescence. Staining for CD31, a marker of endothelial cells, was performed to mark blood vessels. A Cox proportional hazards model was used to assess the prognostic significance of nucleolin. Nucleolin expression was observed in 34.2% of all patients, and 64.1% in high CD31 expression patients. The disease-free survival (DFS) was significantly shorter in patients with high nucleolin (CD31(hi)NCL(hi)) compared to patients with low tumor blood vessels (CD31(lo)NCL(lo)) (5 ys of DFS 24% vs 64%, p = 0.002). Such a difference was demonstrated in the following stratified analyses: stage I (p<0.001), squamous cell carcinoma and adenosquamous cell carcinoma (p = 0.028), small tumor (<5 cm, p = 0.008), and surgery alone (p = 0.015). Multivariate analysis further revealed that nucleolin expression independently predicted for worse survival (p = 0.003). This study demonstrates that nucleolin is associated with the clinical outcomes in postoperative NSCLC patients. Thus, the expression levels of nucleolin may provide a new prognostic marker to identify patients at higher risk for treatment failure, especially in some subgroups. PMID:23382938

  7. Overexpression of SULT2B1b is an independent prognostic indicator and promotes cell growth and invasion in colorectal carcinoma

    PubMed Central

    Hu, Liang; Yang, Guang-Zhen; Zhang, Yu; Feng, Dan; Zhai, Yan-Xia; Gong, Hui; Qi, Chen-Ye; Fu, Hao; Ye, Ming-Ming; Cai, Qing-Ping; Gao, Chun-Fang

    2015-01-01

    Aberrant expression of cytosolic sulfotransferase 2B1b (SULT2B1b) has been reported in several human malignancies. However, the expression pattern and clinical significance of SULT2B1b in colorectal carcinoma (CRC) remains unknown. Real-time quantitative PCR, western blot, and immunohistochemistry analyses were used to determine SULT2B1b expression in CRC clinical samples and CRC-derived cell lines. Kaplan–Meier and Cox proportional regression analyses were used to evaluate the association between SULT2B1b expression and patient survival in two independent cohorts of 485 patients with CRC. Gain- and loss-of-function approaches were employed to investigate the role of SULT2B1b in regulation of CRC cell growth and invasion. We found that SULT2B1b expression was frequently upregulated in CRC clinical samples and CRC-derived cell lines and was significantly correlated with lymph node metastasis and TNM stage in both the training and validation cohorts. Patients with higher intratumoral SULT2B1b expression had a significantly shorter disease-specific survival (DSS) and disease-free survival (DFS) than those with lower expression. Importantly, increased expression of SULT2B1b significantly predicted poor DSS and DFS and was an independent unfavorable prognostic indicator for stage II patients in both cohorts. Functional studies revealed that overexpression of SULT2B1b promoted CRC cell growth and invasion in vitro. Conversely, knockdown of SULT2B1b inhibited these processes. In conclusion, our findings suggest that SULT2B1b expression correlates with disease progression and metastasis and may serve as a novel prognostic biomarker and potential therapeutic target for patients with CRC. PMID:26121319

  8. TP53 overexpression is an independent adverse prognostic factor in de novo myelodysplastic syndromes with fibrosis.

    PubMed

    Loghavi, Sanam; Al-Ibraheemi, Alyaa; Zuo, Zhuang; Garcia-Manero, Guillermo; Yabe, Mariko; Wang, Sa A; Kantarjian, Hagop M; Yin, Cameron C; Miranda, Roberto N; Luthra, Raja; Medeiros, L Jeffrey; Bueso-Ramos, Carlos E; Khoury, Joseph D

    2015-10-01

    Bone marrow (BM) fibrosis is associated with poor prognosis in patients with de novo myelodysplastic syndromes (MDS). TP53 mutations and TP53 (p53) overexpression in MDS are also associated with poor patient outcomes. The prevalence and significance of TP53 mutations and TP53 overexpression in MDS with fibrosis are unknown. We studied 67 patients with de novo MDS demonstrating moderate to severe reticulin fibrosis (MDS-F). Expression of TP53 was evaluated in BM core biopsy specimens using dual-colour CD34/TP53 immunohistochemistry with computer-assisted image analysis. Mutation analysis was performed using next-generation sequencing, or Sanger sequencing methods. TP53 mutations were present in 47·1% of cases. TP53 mutation was significantly associated with TP53 expression (P = 0·0294). High levels of TP53 expression (3 +  in ≥10% cells) were associated with higher BM blast counts (P = 0·0149); alterations of chromosomes 5 (P = 0·0009) or 7 (P = 0·0141); complex karyotype (P = 0·0002); high- and very-high risk IPSS-R groups (P = 0·009); and TP53 mutations (P = 0·0003). High TP53 expression independently predicted shorter overall survival (OS) by multivariate analysis (P = <0·001). Expression of TP53 by CD34-positive cells was associated with shorter OS and leukaemia-free survival (P = 0·0428). TP53 overexpression is a predictor of poor outcome in patients with MDS-F. PMID:26123119

  9. Prognostic significance of geriatric assessment in combination with laboratory parameters in elderly patients with aggressive non-Hodgkin lymphoma.

    PubMed

    Aaldriks, Ab A; Giltay, Erik J; Nortier, Johan W R; van der Geest, Lydia G M; Tanis, Bea C; Ypma, Paula; le Cessie, Saskia; Maartense, Ed

    2015-04-01

    The age-adjusted International Prognostic Index (IPI) is an important prognostic factor for patients with non-Hodgkin lymphoma (NHL). We investigated whether a geriatric assessment (GA) is of additional prognostic value in NHL. In this prospective cohort study of 44 patients aged 70 years or older with NHL receiving rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), a GA was administered before the start of chemotherapy. GA was composed of the Mini Nutritional Assessment (MNA), Groningen Frailty Indicator (GFI), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Mini Mental State Examination (MMSE) and levels of albumin, creatinine, lactate dehydrogenase (LDH) and hemoglobin. Multivariate analyses were performed using logistic regression and the Cox regression model. After adjustment for sex, age, comorbidity and univariate laboratory values with p ≤ 0.1, abnormal MNA and GFI scores and low hemoglobin level were associated with not being able to complete the intended chemotherapy: odds ratio (OR) 8.29 (95% confidence interval [CI]: 1.24-55.6; p = 0.03), 9.17 (95% CI: 1.51-55.8; p = 0.02) and 5.41 (95% CI: 0.99-29.8; p = 0.05), respectively. Adjusted for sex, age, comorbidity, age-adjusted IPI and univariate laboratory values with p ≤ 0.1, frailty by GFI and low hemoglobin were associated with worse survival, with a hazard ratio (HR) of mortality of 2.55 (95% CI: 1.07-6.10; p = 0.04) and 4.90 (95% CI: 1.76-13.7; p = 0.002), respectively. We conclude that (risk of) malnutrition, measured with the MNA, frailty, measured with the GFI, and low hemoglobin level had additional predictive value for early treatment withdrawal, and GFI and hemoglobin were, independent of the age-adjusted IPI, predictive for an increased mortality risk. PMID:24956143

  10. Diagnostic and prognostic significance of the IgM antibody to the Hepatitis delta virus

    SciTech Connect

    Farci, P.; Gerin, J.L.; Aragona, M.; Lindsey, I.; Crivelli, O.; Balestrieri, A.; Smedile, A.; Thomas, H.C.; Rizzetto, M.

    1986-03-21

    The IgM class antibody to the hepatitis delta virus (HDV) was determined in different clinical categories of hepatitis B surface antigen carriers infected by the HDV (positive in the test for total antibody to HDV). The IgM antibody was found at high titers in each 70 patients with inflammatory liver disease and at a low titer in one six patients with inactive cirrhosis; it was not found in eight carriers with normal liver histology. Testing for Igm antibody to HDV distinguishes hepatitis B surface antigen carriers who have underlying inflammatory HDV liver disease from those with past HDV infection and provides prognostic information on the course of chronic HDV hepatitis.

  11. Prognostic significance of heart rate turbulence parameters in patients with chronic heart failure

    PubMed Central

    2014-01-01

    Background This study is aimed to evaluate the clinical significance of heart rate turbulence (HRT) parameters in predicting the prognosis in patients with chronic heart failure (CHF). Methods From June 2011 to December 2012, a total of 104 CHF patients and 30 healthy controls were enrolled in this study. We obtained a 24-hour Holter ECG recording to assess the HRT parameters, included turbulence onset (TO), turbulence slope (TS), standard deviation of N-N intervals (SDNN), and resting heart rate (RHR). The relationships between HRT parameters and the prognosis of CHF patients were determined. Results The assessment follow-up period lasted until January 31, 2013. The overall mortality of CHF patients was 9.6% (10/104). Our results revealed that CHF patients had higher levels of TO than those of healthy subjects, but the TS levels of CHF patients were lower than that of the control group. CHF patients with NYHA grade IV had higher HRT1/2 rate than those with NYHA grade II/III. There were statistical differences in TS, LVEF, SDNN and RHR between the non-deteriorating group and the non-survivor group. Significant differences in TS among the three groups were also found. Furthermore, CHF patients in the non-survivor group had lower levels of TS than those in the deteriorating group. Correlation analyses indicated that TO negatively correlate with SDNN, while TS positively correlated with SDNN and left ventricular ejection fraction (LVEF). We also observed negative correlations between TS and left ventricular end-diastolic cavity dimension (LVEDD), RHR, homocysteine (Hcy) and C-reactive protein (CRP). Multivariate Cox regression analysis further confirmed that LVEF (≤30%), HRT2, SDNN and RHR were independent risk factors which can indicate poor prognosis in CHF patients. Conclusions Our findings indicate that HRT may have good clinical predictive value in patients with CHF. Thus, quantifying HRT parameters could be a useful tool for predicting mortality in CHF

  12. Prognostic significance of the heterogenous expression of IgG Fc receptors in B-cell chronic lymphocytic leukemia.

    PubMed

    Schranz, V; Gráf, F

    1992-03-01

    Receptors for the Fc part of IgG (Fc gamma R) are expressed in three forms on peripheral blood lymphocytes. The presence of the releasable form (Fc gamma R(REL.)) as well as of the two nonreleasable forms with lower (Fc gamma R(LOW)) and higher (Fc gamma R(HIGH)) cellular avidity was correlated with survival in 63 patients with B-cell chronic lymphocytic leukemia (B-CLL). High percentage of cells with Fc gamma R(LOW) as well as high "absolute" number of cells carrying the two nonreleasable forms of Fc gamma R were connected to unfavorable prognosis. Combining these three parameters, an Fc gamma R constellation was defined which pointed to a favorable prognosis (in 24 patients) when all three parameters were low, but detected short survivors when all three data were high (in 14 patients). The Fc gamma R constellation was capable of identifying patients with better or worse prognosis within groups that were homogeneous regarding some other known prognostic factors. Fc gamma R constellation as a prognostic factor was shown to be independent of age, sex, and Rai and Binet stages, but it was found to be connected with the total tumor mass score (TTM). The three forms of Fc gamma R on B cells might reflect stages of B-cell activation. Differences in Fc gamma R constellations between patients with B-CLL would thus correspond to differently activated B-cell clones with variable prognosis. PMID:1571409

  13. Prognostic Significance of Tumor Hypoxia Inducible Factor-1{alpha} Expression for Outcome After Radiotherapy in Oropharyngeal Cancer

    SciTech Connect

    Silva, Priyamal; Slevin, Nick J.; Sloan, Philip; Valentine, Helen; Cresswell, Jo; Ryder, David; Price, Patricia; Homer, Jarrod J.; West, Catharine

    2008-12-01

    Purpose: Head-and-neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of patients in terms of subsite, treatment, and biology. Currently most management decisions are based on clinical parameters with little appreciation of patient differences in underlying tumor biology. We investigated the prognostic significance of clinicopathologic features and tumor hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) expression in a homogeneous series of patients who underwent radiotherapy. Methods and Materials: An audit identified 133 consecutive patients with histologically proven squamous cell carcinoma of the tonsil or tongue base. All patients received primary radiotherapy between 1996 and 2001. Tumor HIF-1{alpha} expression was examined in 79 patients. Results: Features associated with poor locoregional control were low Hb level (p = 0.05) and advancing T (p = 0.008), N (p = 0.03), and disease (p = 0.008) stage. HIF-1{alpha} expression was a more significant adverse prognostic factor in the tonsil (hazard ratio [HR], 23.1; 95% confidence interval [CI]. 3.04-176.7) than the tongue-base tumor (HR, 2.86; 95% CI, 1.14-7.19) group (p = 0.03, test for interaction). High tumor HIF-1{alpha} expression was associated with low blood Hb levels (p = 0.03). In a multivariate analysis HIF-1{alpha} expression retained prognostic significance for locoregional control (HR, 7.10; 95% CI, 3.07-16.43) and cancer-specific survival (HR, 9.19; 95% CI, 3.90-21.6). Conclusions: There are significant differences in radiation therapy outcome within a homogeneous subsite of the oropharynx related to molecular marker expression. The work highlights the importance of studying homogeneous groups of patients in HNSCC, and the complex interrelationships between tumor biology and clinicopathologic factors. The establishment of tumor-type specific markers would represent a major advance in this area.

  14. High expression of peroxiredoxin 4 affects the survival time of colorectal cancer patients, but is not an independent unfavorable prognostic factor

    PubMed Central

    YI, NAN; XIAO, MING BING; NI, WEN KAI; JIANG, FENG; LU, CUI HUA; NI, RUN-ZHOU

    2014-01-01

    Peroxiredoxin 4 (Prx4) has a number of important biological functions, such as efficient antioxidant capacity and promotion of cell proliferation and differentiation. The purpose of this study was to investigate the expression and significance of Prx4 in human colorectal cancer (CRC). Quantitative polymerase chain reaction (qPCR) was performed to detect Prx4 in 8 freshly frozen specimens of CRC and their adjacent normal tissues. In addition, immunohistochemical analysis was performed to detect Prx4 in 59 specimens of CRC and 26 of adjacent normal tissues. The immunohistochemical and qPCR results demonstrated that the expressions of the Prx4 gene and protein were higher in CRC compared to those in the adjacent normal tissues. The expression intensity of the Prx4 protein was correlated with depth of invasion (P=0.001), lymph node metastasis (P=0.006) and Dukes’ classification (P=0.004) in CRC. The Kaplan-Meier survival curves revealed that high Prx4 expression was correlated with short survival time. However, the Cox proportional hazards regression analysis did not identify Prx4 as an independent prognostic marker for CRC (P>0.05). These results suggested that Prx4 may be associated with carcinogenesis and the development of CRC and it may be a prognostic marker for postoperative CRC patients. PMID:25054044

  15. Zinc finger protein ZBTB20 is an independent prognostic marker and promotes tumor growth of human hepatocellular carcinoma by repressing FoxO1

    PubMed Central

    Kan, Heping; Huang, Yuqi; Li, Xianghong; Liu, Dingli; Chen, Jianjia; Shu, Miaojiang

    2016-01-01

    Zinc finger and BTB domain-containing 20 (ZBTB20) is a new BTB/POZ-domain gene and a member of the POK family of transcriptional repressors. Notably, the role of ZBTB20 and its underlying mechanisms involved in hepatocarcinogenesis are poorly investigated. In this study, the expression of ZBTB20 was significantly overexpressed in hepatocellular carcinoma (HCC) tissues. The positive expression of ZBTB20 was associated with large tumor size, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage. Additionally, HCC patients with positive expression of ZBTB20 had a poorer 5-year survival. Multivariate analyses revealed that ZBTB20 overexpression was an independent prognostic factor for HCC. Gain- and loss-of-function experiments demonstrated that ZBTB20 promoted HCC cell viability, proliferation, tumorigenicity, and cell cycle progression. Mechanistically, Cyclin D1 and Cyclin E were increased, while p21 and p27 were decreased by ZBTB20 in HCC cells. FoxO1 was inversely correlated with ZBTB20 protein expression in the same cohort of HCC specimens. We further revealed that FoxO1 was transcriptionally repressed by ZBTB20 in HCC. Moreover, restoration of FoxO1 expression partially abrogated ZBTB20-induced HCC cell proliferation and growth entry in vitro and in vivo. Collectively, these results indicate that ZBTB20 may serve as a prognostic marker and promotes tumor growth of HCC via transcriptionally repressing FoxO1. PMID:26893361

  16. Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1, 2 and 3 in Periampullary Adenocarcinoma

    PubMed Central

    Heby, Margareta; Warfvinge, Carl Fredrik; Nodin, Björn; Eberhard, Jakob; Jirström, Karin

    2016-01-01

    Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumours with dismal prognosis, for which there is an urgent need to identify novel treatment strategies. The human epithelial growth factor receptors EGFR, HER2 and HER3 have been studied in several tumour types, and HER-targeting drugs have a beneficial effect on survival in selected types of cancer. However, these effects have not been evident in pancreatic cancer, and remain unexplored in other types of periampullary cancer. The prognostic impact of HER-expression in these cancers also remains unclear. The aim of this study was therefore to examine the expression and prognostic value of EGFR, HER2 and HER3 in periampullary cancer, with particular reference to histological subtype. To this end, protein expression of EGFR, HER2 and HER3, and HER2 gene amplification was assessed by immunohistochemistry and silver in situ hybridization, respectively, on tissue microarrays with tumours from 175 periampullary adenocarcinomas, with follow-up data on recurrence-free survival (RFS) and overall survival (OS) for up to 5 years. EGFR expression was similar in pancreatobiliary (PB) and intestinal (I) type tumours, but high HER2 and HER3 expression was significantly more common in I-type tumours. In PB-type cases receiving adjuvant gemcitabine, but not in untreated cases, high EGFR expression was significantly associated with a shorter OS and RFS, with a significant treatment interaction in relation to OS (pinteraction = 0.042). In I-type cases, high EGFR expression was associated with a shorter OS and RFS in univariable, but not in multivariable, analysis. High HER3 expression was associated with a prolonged RFS in univariable, but not in multivariable, analysis. Neither HER2 protein expression nor gene amplification was prognostic. The finding of a potential interaction between the expression of EGFR and response to adjuvant chemotherapy in PB-type tumours needs validation, and merits

  17. Facility characteristics as independent prognostic factors of nursing home-acquired pneumonia

    PubMed Central

    Lim, Che Wan; Choi, Younghoon; An, Chang Hyeok; Park, Sang Joon; Hwang, Hee-Jin; Chung, Jae Ho; Min, Joo-Won

    2016-01-01

    Background/Aims: Recently, the incidence of nursing home-acquired pneumonia (NHAP) has been increasing and is now the leading cause of death among nursing home residents. This study was performed to identify risk factors associated with NHAP mortality, focusing on facility characteristics. Methods: Data on all patients ≥ 70 years of age admitted with newly diagnosed pneumonia were reviewed. To compare the quality of care in nursing facilities, the following three groups were defined: patients who acquired pneumonia in the community, care homes, and care hospitals. In these patients, 90-day mortality was compared. Results: Survival analyses were performed in 282 patients with pneumonia. In the analyses, 90-day mortality was higher in patients in care homes (12.2%, 40.3%, and 19.6% in community, care homes, and care hospitals, respectively). Among the 118 NHAP patients, residence in a care home, structural lung diseases, treatment with inappropriate antimicrobial agents for accompanying infections, and a high pneumonia severity index score were risk factors associated with higher 90-day mortality. However, infection by potentially drug-resistant pathogens was not important. Conclusions: Unfavorable institutional factors in care homes are important prognostic factors for NHAP. PMID:26837007

  18. Clinicopathological and Prognostic Significance of Survivin Expression in Patients with Oral Squamous Cell Carcinoma: Evidence from a Meta-Analysis

    PubMed Central

    Xie, Shang; Xu, Hui; Shan, Xiaofeng; Liu, Baozhong; Wang, Kan; Cai, Zhigang

    2015-01-01

    Background Survivin has been proposed as a promising prognostic marker in oral squamous cell carcinoma (OSCC), but the published data on survivin expression in patients with this condition are controversial. To address this we performed a meta-analysis systematically to assess the clinicopathological and prognostic significance of survivin expression in OSCC. Methods We searched PubMed, Embase, Web of Science and Ovid databases for papers investigating the clinicopathological and prognostic significance of survivin expression in OSCC. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to determine the relevance of survivin. Results A total of 15 papers, including 1040 cases in which survivin expression was detected by immunohistochemistry (IHC) or reverse transcription polymerase chain reaction (RT-PCR), were included. A meta-analysis of clinicopathological variables revealed a correlation between survivin expression and lymph node metastasis (OR = 0.62, 95% CI = 0.44–0.88, p < 0.05) and clinical stage (OR = 0.63, 95% CI = 0.41–0.96, p < 0.05). However, no significant associations were found between survivin expression and tumor differentiation grade (OR = 0.72, 95%CI = 0.26–1.11, p > 0.05), depth of invasion (OR = 0.76, 95% CI = 0.50–1.14, p > 0.05), age (OR = 0.78, 95% CI = 0.48–1.29, p > 0.05) or gender (OR = 1.31, 95% CI = 0.86–2.01, p > 0.05). Subgroup analysis using stratified detection methods showed no significant associations between the expression of survivin protein and clinicopathological variables in OSCC. A correlation between survivin expression and poor prognosis of patients with OSCC (HR = 1.62, 95% CI = 1.23–2.01, p < 0.05) was demonstrated. Conclusion Survivin is a potential prognostic marker of OSCC. Future studies with larger sample sizes and well-designed inclusion criteria will be needed to dissect the role of survivin expression in determining the clinicopathological features and

  19. Prognostic significance of computed tomography-detected extramural vascular invasion in colon cancer

    PubMed Central

    Yao, Xun; Yang, Su-Xing; Song, Xing-He; Cui, Yan-Cheng; Ye, Ying-Jiang; Wang, Yi

    2016-01-01

    AIM To compare disease-free survival (DFS) between extramural vascular invasion (EMVI)-positive and -negative colon cancer patients evaluated by computed tomography (CT). METHODS Colon cancer patients (n = 194) undergoing curative surgery between January 2009 and December 2013 were included. Each patient’s demographics, cancer characteristics, EMVI status, pathological status and survival outcomes were recorded. All included patients had been routinely monitored until December 2015. EMVI was defined as tumor tissue within adjacent vessels beyond the colon wall as seen on enhanced CT. Disease recurrence was defined as metachronous metastases, local recurrence, or death due to colon cancer. Kaplan-Meier analyses were used to compare DFS between the EMVI-positive and -negative groups. Cox’s proportional hazards models were used to measure the impact of confounding variables on survival rates. RESULTS EMVI was observed on CT (ctEMVI) in 60 patients (30.9%, 60/194). One year after surgery, there was no statistically significant difference regarding the rates of progressive events between EMVI-positive and -negative patients [11.7% (7/60) and 6.7% (9/134), respectively; P = 0.266]. At the study endpoint, the EMVI-positive patients had significantly more progressive events than the EMVI-negative patients [43.3% (26/60) and 14.9% (20/134), respectively; odds ratio = 4.4, P < 0.001]. Based on the Kaplan-Meier method, the cumulative 1-year DFS rates were 86.7% (95%CI: 82.3-91.1) and 92.4% (95%CI: 90.1-94.7) for EMVI-positive and EMVI-negative patients, respectively. The cumulative 3-year DFS rates were 49.5% (95%CI: 42.1-56.9) and 85.8% (95%CI: 82.6-89.0), respectively. Cox proportional hazards regression analysis revealed that ctEMVI was an independent predictor of DFS with a hazard ratio of 2.15 (95%CI: 1.12-4.14, P = 0.023). CONCLUSION ctEMVI may be helpful when evaluating disease progression in colon cancer patients.

  20. Prognostic Significance of β-Catenin, E-Cadherin, and SOX9 in Colorectal Cancer: Results from a Large Population-Representative Series

    PubMed Central

    Bruun, Jarle; Kolberg, Matthias; Nesland, Jahn M.; Svindland, Aud; Nesbakken, Arild; Lothe, Ragnhild A.

    2014-01-01

    Robust biomarkers that can precisely stratify patients according to treatment needs are in great demand. The literature is inconclusive for most reported prognostic markers for colorectal cancer (CRC). Hence, adequately reported studies in large representative series are necessary to determine their clinical potential. We investigated the prognostic value of three Wnt signaling-associated proteins, β-catenin, E-cadherin, and SOX9, in a population-representative single-hospital series of 1290 Norwegian CRC patients by performing immunohistochemical analyses of each marker using the tissue microarray technology. Loss of membranous or cytosolic β-catenin and loss of cytosolic E-cadherin protein expression were significantly associated with reduced 5-year survival in 903 patients who underwent major resection (722 evaluable tissue cores) independently of standard clinicopathological high-risk parameters. Pre-specified subgroup analyses demonstrated particular effect for stage IV patients for β-catenin membrane staining (P = 0.018; formal interaction test P = 0.025). Among those who underwent complete resection (714 patients, 568 evaluable), 5-year time-to-recurrence analyses were performed, and stage II patients with loss of cytosolic E-cadherin were identified as an independent high-risk subgroup (P = 0.020, formal interaction test was not significant). Nuclear β-catenin and SOX9 protein, regardless of intracellular location, were not associated with prognosis. In conclusion, the protein expression level of membranous or cytosolic β-catenin and E-cadherin predicts CRC patient subgroups with inferior prognosis. PMID:24904831

  1. Prognostic and Predictive Significance of Stromal Fibroblasts and Macrophages in Colon Cancer

    PubMed Central

    Owusu, Benjamin Y.; Vaid, Mudit; Kaler, Pawan; Klampfer, Lidija

    2015-01-01

    Colon cancer development and malignant progression are driven by genetic and epigenetic alterations in tumor cells and by factors from the tumor microenvironment. Cancer cells become reliant on the activity of specific oncogenes and on prosurvival and proliferative signals they receive from the abnormal environment they create and reside in. Accordingly, the response to anticancer therapy is determined by genetic and epigenetic changes that are intrinsic to tumor cells and by the factors present in the tumor microenvironment. Recent advances in the understanding of the involvement of the tumor microenvironment in tumor progression and therapeutic response are optimizing the application of prognostic and predictive factors in colon cancer. Moreover, new targets in the tumor microenvironment that are amenable to therapeutic intervention have been identified. Because stromal cells are with rare exceptions genetically stable, the tumor microenvironment has emerged as a preferred target for therapeutic drugs. In this review, we discuss the role of stromal fibroblasts and macrophages in colon cancer progression and in the response of colon cancer patients to therapy. PMID:26568685

  2. The prognostic significance of specific HOX gene expression patterns in ovarian cancer.

    PubMed

    Kelly, Zoe; Moller-Levet, Carla; McGrath, Sophie; Butler-Manuel, Simon; Kavitha Madhuri, Thumuluru; Kierzek, Andrzej M; Pandha, Hardev; Morgan, Richard; Michael, Agnieszka

    2016-10-01

    HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials. PMID:27225067

  3. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance

    PubMed Central

    Stål, Per

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD. PMID:26494963

  4. Prognostic Significance of Circulating Tumor Cells in Non-Small-Cell Lung Cancer Patients: A Meta-Analysis

    PubMed Central

    Huang, Jianwei; Wang, Ke; Xu, Jianjun; Huang, Jian; Zhang, Tao

    2013-01-01

    Background The prognostic significance of circulating tumor cells (CTCs) detected in patients with non-small-cell lung cancer (NSCLC) is still inconsistent. We aimed to assess the prognostic relevance of CTCs using a meta-analysis. Methods We searched PubMed, Web of Science and EMBASE for relevant studies that assessed the prognostic relevance of CTCs in NSCLC. Statistical analyses were conducted to calculate the summary incidence, odds ratio, relative risks (RRs) and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies. Results A total of 20 studies, comprising 1576 patients, met the inclusion criteria. In identified studies, CTCs were not correlated with histology (adenocarcinoma vs squamous cell carcinoma) (odds ratio [OR]  =  0.88; 95% confidence interval [CI]: 0.59–1.33; Z = –0.61; P = 0.545). However, pooled analyses showed that CTCs were associated with lymph node metastasis (OR = 2.06; 95% CI: 1.18–3.62; Z = 2.20; P = 0.027) and tumor stage (OR  = 1.95; 95% CI: 1.08–3.54; Z = 2.53; P = 0.011). Moreover, CTCs were significantly associated with shorter overall survival (relative risk [RR]  = 2.19; 95% CI: 1.53–3.12; Z = 4.32; P<0.0001) and progression-free/disease-free survival (RR  = 2.14; 95% CI: 1.36–3.38; Z = 3.28; P<0.0001). Conclusion The presence of CTCs indicates a poor prognosis in patients with NSCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in lung cancer. PMID:24223761

  5. The prognostic significance of the 2014 International Society of Urological Pathology (ISUP) grading system for prostate cancer.

    PubMed

    Samaratunga, Hemamali; Delahunt, Brett; Gianduzzo, Troy; Coughlin, Geoff; Duffy, David; LeFevre, Ian; Johannsen, Shulammite; Egevad, Lars; Yaxley, John

    2015-10-01

    The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters.Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32-79 years). Median serum prostate specific antigen was 5.9 (range 0.4-69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1-5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS.This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate. PMID:26325670

  6. Complement Component 1, s Subcomponent Overexpression is an Independent Poor Prognostic Indicator in Patients with Urothelial Carcinomas of the Upper Urinary Tract and Urinary Bladder

    PubMed Central

    Chang, I-Wei; Lin, Victor Chia-Hsiang; Wu, Wen-Jen; Liang, Peir-In; Li, Wei-Ming; Yeh, Bi-Wen; He, Hong-Lin; Liao, Alex Chien-Hwa; Chan, Ti-Chun; Li, Chien-Feng

    2016-01-01

    Purpose: Urothelial carcinoma of the urinary bladder and upper tract is prevalent. By subjecting a documented transcriptome data set of urothelial carcinoma of bladder (GSE31684) to data mining and focusing on genes linked to peptidase activity (GO:0008233), we recognized C1S as the most significantly upregulated gene related to an advanced tumor status and metastasis. We subsequently analyzed the association of both C1S mRNA and its encoded protein expression with the clinical and pathological significance. Materials and Methods: We used real-time reverse transcription polymerase chain reaction to detect C1S transcription levels in 20 cases each of urothelial carcinoma of bladder and upper tract. An immunohistochemical stain was conducted to determine C1s protein expression levels in patients with urothelial carcinoma of upper tract (n = 340) and urinary bladder (n = 295). Furthermore, we examined the correlation of C1s expression with clinicopathological characteristics, disease-specific survival, and metastasis-free survival. Results: C1S transcription levels were significantly high in patients with advanced-stage tumors of both groups (all P < .05). Immunohistochemical analysis revealed that C1s expression levels were significantly associated with adverse clinicopathological parameters in both groups of urothelial carcinoma (all P < .05). C1s overexpression predicted poor disease-specific and metastasis-free survival rates for both urothelial carcinoma groups in the univariate analysis, and it was also an independent prognostic factor in the multivariate analysis (all P < .05). Conclusions: C1s may play a pivotal role in urothelial carcinoma progress and can represent a vital prognostic marker and a promising new therapeutic target in urothelial carcinoma. PMID:27471555

  7. Prognostic Significance of Telomere Maintenance Mechanisms in Pediatric High-Grade Gliomas

    PubMed Central

    Dorris, Kathleen; Sobo, Matthew; Onar-Thomas, Arzu; Panditharatna, Eshini; Stevenson, Charles B.; Gardner, Sharon L.; DeWire, Mariko D.; Pierson, Christopher R.; Olshefski, Randal; Rempel, Sandra A.; Goldman, Stewart; Miles, Lili; Fouladi, Maryam; Drissi, Rachid

    2014-01-01

    Background Children with high-grade glioma, including diffuse intrinsic pontine glioma (DIPG), have a poor prognosis despite multimodal therapy. Identifying novel therapeutic targets is critical to improve their outcome. We evaluated prognostic roles of telomere maintenance mechanisms in children with HGG, including DIPG. Methods A multi-institutional retrospective study was conducted involving 50 flash-frozen HGG (35 non-brainstem; 15 DIPG) tumors from 45 children (30 non-brainstem; 15 DIPG). Telomerase activity, expression of hTERT mRNA (encoding telomerase catalytic component) and TERC (telomerase RNA template) and alternative lengthening of telomeres (ALT) mechanism were assayed. Cox Proportional Hazard regression analyses assessed association of clinical and pathological variables, TERC and hTERT levels, telomerase activity, and ALT use with progression-free or overall survival (OS). Results High TERC and hTERT expression was detected in 13/28 non-brainstem HGG samples as compared to non-neoplastic controls. High TERC and hTERT expression was identified in 13/15 and 11/15 DIPG samples, respectively, compared to controls. Evidence of ALT was noted in 3/11 DIPG and 10/19 non-brainstem HGG specimens. ALT and telomerase use were identified in 4/19 non-brainstem HGG and 2/11 DIPG specimens. In multivariable analyses, increased TERC and hTERT levels were associated with worse OS in patients with non-brainstem HGG, after controlling for tumor grade or resection extent. Conclusions Children with HGG and DIPG, have increased hTERT and TERC expression. In children with non-brainstem HGG, increased TERC and hTERT expression levels are associated with a worse OS, making telomerase a promising potential therapeutic target in pediatric HGG. PMID:24477622

  8. High expression of the Ets-related gene (ERG) is an independent prognostic marker for relapse-free survival in patients with acute promyelocytic leukemia.

    PubMed

    Hecht, Anna; Nowak, Daniel; Nowak, Verena; Hanfstein, Benjamin; Faldum, Andreas; Büchner, Thomas; Spiekermann, Karsten; Sauerland, Cristina; Lengfelder, Eva; Hofmann, Wolf-Karsten; Nolte, Florian

    2013-04-01

    In acute promyelocytic leukemia (APL), relapse occurs in about 15 % of cases and is a major cause for death. Molecular markers identifying patients at high risk for relapse are not well established. High expression of the transcription factor Ets-related gene (ERG) is associated with inferior overall survival (OS) and disease-free survival in different types of hematologic malignancies. There are no data available about the impact of ERG expression in APL. ERG expression levels were analyzed in bone marrow samples of 86 APL patients at initial diagnosis. High ERG expression was significantly associated with an inferior OS in patients who had reached first complete remission. It was also significantly correlated with inferior relapse-free survival (RFS) and time to relapse (i.e., relapse-free interval, RFI). In multivariate analysis, high ERG expression had an independent negative impact on RFS and RFI. High ERG expression was significantly associated with inferior OS, RFS, and RFI. Moreover, in multivariate analysis, it maintained its value as an independent negative prognostic factor with regard to RFS and RFI. Therefore, ERG expression might serve as a molecular marker for risk stratification in APL and might identify patients who could benefit from intensified treatment regimens. PMID:23250622

  9. Overexpression of CIP2A is an independent prognostic indicator in nasopharyngeal carcinoma and its depletion suppresses cell proliferation and tumor growth

    PubMed Central

    2014-01-01

    Background Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a prognostic marker for several human malignancies. In this study, we investigated the clinical significance of CIP2A and its function in nasopharyngeal carcinoma (NPC). Methods Quantitative RT-PCR, western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in NPC cell lines and clinical samples. Kaplan-Meier curves were used to estimate the association between CIP2A expression and patient survival. The functional role of CIP2A in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and xenograft growth. Results CIP2A levels were upregulated in NPC cell lines and clinical samples at both the mRNA and protein levels (P < 0.01). Patients with high CIP2A expression had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and poorer disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) rates than patients with low CIP2A expression. In addition, CIP2A expression status was an independent prognostic indicator for NPC patients. The depletion of CIP2A expression inhibited c-Myc protein expression in NPC cell lines, suppressed cell viability, colony formation, and anchorage-independent growth in vitro, and inhibited xenograft tumor growth in vivo. Conclusions Our data demonstrate that high CIP2A expression in patients was associated with poor survival in NPC, and depletion of CIP2A expression inhibited NPC cell proliferation and tumor growth. Thus, these results warrant further investigation of CIP2A as a novel therapeutic target for the treatment of NPC. PMID:24884612

  10. Bax expression has prognostic significance that is enhanced when combined with AgNOR counts in glottic carcinomas.

    PubMed Central

    Xie, X.; Clausen, O. P.; De Angelis, P.; Boysen, M.

    1998-01-01

    Using nucleolar organizer regions (NORs) as a proliferative marker and Bax expression as a marker for apoptosis, we have studied the individual and combined prognostic significance of these markers. Successive sections of diagnostic, formalin-fixed and paraffin-embedded specimens from 69 patients with T1-4 tumours were stained with a rabbit anti-human Bax polyclonal antibody and silver nitrate for visualization of NORs (AgNORs). After classification for staining intensity and the percentage of Bax expression, a final score resulting in four classes of increasing Bax expression was obtained. AgNOR counts were expressed as mean counts (mAgNOR) and the percentage of tumour nuclei with more than one AgNOR (pAgNOR>1). Both AgNOR parameters were grouped in three classes with increasing values. Low Bax scores correlated significantly with poor prognosis (P = 0.0106). For mAgNOR and pAgNOR>1, high values correlated with poor prognosis (P = 0.0185 and P = 0.0003 respectively). A combined parameter, for which the Bax score was subtracted from the AgNOR scores, appeared to be statistically stronger than the individual parameters (P < 0.0001). Both Bax expression and AgNOR scores, and in particular the combination of these parameters, appear to be strong prognostic markers in glottic squamous cell carcinomas. PMID:9662258

  11. Metabonomics Analysis of Plasma Reveals the Lactate to Cholesterol Ratio as an Independent Prognostic Factor of Short-Term Mortality in Acute Heart Failure

    PubMed Central

    Desmoulin, Franck; Galinier, Michel; Trouillet, Charlotte; Berry, Matthieu; Delmas, Clément; Turkieh, Annie; Massabuau, Pierre; Taegtmeyer, Heinrich; Smih, Fatima; Rouet, Philippe

    2013-01-01

    Objective Mortality in heart failure (AHF) remains high, especially during the first days of hospitalization. New prognostic biomarkers may help to optimize treatment. The aim of the study was to determine metabolites that have a high prognostic value. Methods We conducted a prospective study on a training cohort of AHF patients (n = 126) admitted in the cardiac intensive care unit and assessed survival at 30 days. Venous plasmas collected at admission were used for 1H NMR–based metabonomics analysis. Differences between plasma metabolite profiles allow determination of discriminating metabolites. A cohort of AHF patients was subsequently constituted (n = 74) to validate the findings. Results Lactate and cholesterol were the major discriminating metabolites predicting 30-day mortality. Mortality was increased in patients with high lactate and low total cholesterol concentrations at admission. Accuracies of lactate, cholesterol concentration and lactate to cholesterol (Lact/Chol) ratio to predict 30-day mortality were evaluated using ROC analysis. The Lact/Chol ratio provided the best accuracy with an AUC of 0.82 (P < 0.0001). The acute physiology and chronic health evaluation (APACHE) II scoring system provided an AUC of 0.76 for predicting 30-day mortality. APACHE II score, Cardiogenic shock (CS) state and Lact/Chol ratio ≥ 0.4 (cutoff value with 82% sensitivity and 64% specificity) were significant independent predictors of 30-day mortality with hazard ratios (HR) of 1.11, 4.77 and 3.59, respectively. In CS patients, the HR of 30-day mortality risk for plasma Lact/Chol ratio ≥ 0.4 was 3.26 compared to a Lact/Chol ratio of < 0.4 (P  =  0.018). The predictive power of the Lact/Chol ratio for 30-day mortality outcome was confirmed with the independent validation cohort. Conclusion This study identifies the plasma Lact/Chol ratio as a useful objective and simple parameter to evaluate short term prognostic and could be integrated into quantitative

  12. Prognostic significance of p62/SQSTM1 subcellular localization and LC3B in oral squamous cell carcinoma

    PubMed Central

    Liu, J-L; Chen, F-F; Lung, J; Lo, C-H; Lee, F-H; Lu, Y-C; Hung, C-H

    2014-01-01

    Background: Autophagy is a programmed cell survival mechanism that has a key role in both physiologic and pathologic conditions. The relationship between autophagy and cancer is complex because autophagy can act as either a tumour suppressor or as a tumour promoter. The role of autophagy in oral squamous cell carcinoma (OSCC) is controversial. Several studies have claimed that either a high or low expression of autophagy-related proteins was associated with poor prognosis of OSCCs. The aims of the study were to compare autophagy in OSCCs, verrucous hyperplasias, and normal oral mucosas, and to inspect the prognostic role of autophagy in OSCCs. Methods: We used the autophagosome marker, LC3B, and autophagy flux marker, p62/SQSTM1 (p62), by using immunohistochemistry, and examined p62 mRNA by RNA in situ hybridization, to evaluate autophagy in 195 OSCCs, 47 verrucous hyperplasias, and 37 normal oral mucosas. The prognostic roles of LC3B and p62 protein expressions in OSCCs were investigated. Results: We discovered that the normal oral mucosa exhibited limited LC3B punctae and weak cytoplasmic p62 staining, whereas the OSCCs exhibited a marked increase in LC3B punctae and cytoplasmic p62 expression. The expression pattern of LC3B and cytoplasmic p62 of the verrucous hyperplasias were between normal oral mucosas and OSCCs. The normal oral mucosas, verrucous hyperplasias, and OSCCs presented no differences in nuclear p62 expression and the p62 mRNA level. p62 mRNA expression was elevated in a minority of cases. High p62 mRNA expression was associated with high p62 protein expression in the cytoplasm. Increased LC3B punctae, high cytoplasmic p62, and low nuclear p62 expressions in OSCCs were associated with aggressive clinicopathologic features and unfavourable prognosis. In addition, low nuclear p62 expression was an independent prognostic factor for overall and disease-specific survival rates. Furthermore, we disclosed that high cytoplasmic p62 expression accompanied

  13. Reversing HOXA9 Oncogene Activation by PI3K Inhibition: Epigenetic Mechanism and Prognostic Significance in Human Glioblastoma

    PubMed Central

    Costa, Bruno M.; Smith, Justin S.; Chen, Ying; Chen, Justin; Phillips, Heidi S.; Aldape, Kenneth D.; Zardo, Giuseppe; Nigro, Janice; James, C. David; Fridlyand, Jane; Reis, Rui M.; Costello, Joseph F.

    2010-01-01

    HOXA genes encode critical transcriptional regulators of embryonic development that have been implicated in cancer. In this study, we documented functional relevance and mechanism of activation of HOXA9 in glioblastoma (GBM), the most common malignant brain tumor. Expression of HOXA genes was investigated using RT-PCR in primary gliomas and glioblastoma cell lines and was validated in two sets of expression array data. In a subset of GBM, HOXA genes are aberrantly activated within confined chromosomal domains. Transcriptional activation of the HOXA cluster was reversible by a PI3K inhibitor through an epigenetic mechanism involving histone H3K27 trimethylation. Functional studies of HOXA9 showed its capacity to decrease apoptosis and increase cellular proliferation along with TRAIL resistance. Notably, aberrant expression of HOXA9 was independently predictive of shorter overall and progression-free survival in two GBM patient sets, and improved survival prediction by MGMT promoter methylation. Thus, HOXA9 activation is a novel, independent and negative prognostic marker in GBM that is reversible through a PI3K-associated epigenetic mechanism. Our findings suggest a transcriptional pathway through which PI3K activates oncogenic HOXA expression with implications for mTOR or PI3K targeted therapies. PMID:20068170

  14. Reversing HOXA9 oncogene activation by PI3K inhibition: epigenetic mechanism and prognostic significance in human glioblastoma.

    PubMed

    Costa, Bruno M; Smith, Justin S; Chen, Ying; Chen, Justin; Phillips, Heidi S; Aldape, Kenneth D; Zardo, Giuseppe; Nigro, Janice; James, C David; Fridlyand, Jane; Reis, Rui M; Costello, Joseph F

    2010-01-15

    HOXA genes encode critical transcriptional regulators of embryonic development that have been implicated in cancer. In this study, we documented functional relevance and mechanism of activation of HOXA9 in glioblastoma (GBM), the most common malignant brain tumor. Expression of HOXA genes was investigated using reverse transcription-PCR in primary gliomas and glioblastoma cell lines and was validated in two sets of expression array data. In a subset of GBM, HOXA genes are aberrently activated within confined chromosomal domains. Transcriptional activation of the HOXA cluster was reversible by a phosphoinostide 3-kinase (PI3K) inhibitor through an epigenetic mechanism involving histone H3K27 trimethylation. Functional studies of HOXA9 showed its capacity to decrease apoptosis and increase cellular proliferation along with tumor necrosis factor-related apoptosis-including ligand resistance. Notably, aberrant expression of HOXA9 was independently predictive of shorter overall and progression-free survival in two GBM patient sets and improved survival prediction by MGMT promoter methylation. Thus, HOXA9 activation is a novel, independent, and negative prognostic marker in GBM that is reversible through a PI3K-associated epigenetic mechanism. Our findings suggest a transcriptional pathway through which PI3K activates oncogenic HOXA expression with implications for mTOR or PI3K targeted therapies. PMID:20068170

  15. Pretreatment whole blood Epstein-Barr virus-DNA is a significant prognostic marker in patients with Hodgkin lymphoma.

    PubMed

    Park, Ji Hyun; Yoon, Dok Hyun; Kim, Shin; Park, Jung Sun; Park, Chan-Sik; Sung, Heungsup; Lee, Sang-Wook; Huh, Jooryung; Suh, Cheolwon

    2016-04-01

    Epstein-Barr virus (EBV) in the peripheral blood has become a significant predictor of clinical outcomes in EBV-associated Hodgkin lymphoma (HL). However, due to its relative rarity, prevalence and prognostic role of circulating EBV-DNA has not been well established in Asian patients. Seventy patients with newly diagnosed HL were prospectively registered between October 2007 and January 2013, and underwent pretreatment whole blood (WB) EBV-DNA quantitation using real-time polymerase chain reaction (RT-PCR). WB EBV-DNA in baseline and serial RT-PCR within 1 year were investigated. Clinicopathologic parameters of the patients according to pretreatment WB EBV-DNA were also explored. Twelve patients (17.1 %) demonstrated WB EBV-DNA(+), which was significantly associated to older age, advanced stages, frequent involvements of extranodal sites, low serum albumin and hemoglobin levels, and high international prognostic scores ≥2. Three-year event-free survival (EFS) and overall survival (OS) were significantly inferior in patients with pretreatment WB EBV-DNA(+) (53.5 vs 67.0 and 65.6 vs 90.2 %) (p < 0.032 and <0.01). Negatively conversed EBV-DNA within 1 year after chemotherapy also significantly affected favorable EFS (p < 0.01). Taken together, pretreatment WB EBV-DNA(+) may be a significant predictor of inferior EFS and OS over EBV-encoded RNA in situ hybridization (EBER-ISH)(+) in Korean patients with HL. Serial EBV-DNA monitoring following chemotherapy also seems helpful to predict survival outcomes. PMID:26883027

  16. Prognostic Significance of Serine-Phosphorylated STAT3 Expression in pT1-T2 Oral Tongue Carcinoma

    PubMed Central

    Staffieri, Claudia; Cappellesso, Rocco; Marino, Filippo; Ottaviano, Giancarlo; Val, Matteo; Giacomelli, Luciano; de Filippis, Cosimo; Stellini, Edoardo; Staffieri, Alberto; Marioni, Gino

    2015-01-01

    Objectives Phosphorylated (activated) STAT3 (pSTAT3) is a regulator of numerous genes that play an essential part in the onset, development and progression of cancer; it is involved in cell proliferation and preventing apoptosis, and in invasion, angiogenesis, and the evasion of immune surveillance. This study aimed mainly to investigate the potential prognostic role of pSTAT3 expression in oral tongue squamous cell carcinoma (SCC). Methods Phospho-ser727 STAT3 immunolabeling was correlated with prognostic parameters in 34 consecutive cases of pT1-T2 tongue SCCs undergoing primary surgery. Computer-based image analysis was used for the immunohistochemical reactions analysis. Results Statistical analysis showed a difference in disease-free survival (DFS) when patients were stratified by pN status (P=0.031). Most tumors had variable degrees (mean±SD, 80.7%±23.8%) of intense nuclear immunoreaction to pSTAT3. Our findings rule out any significant association of serine-phosphorylated nuclear STAT3 expression with tumor stage, grade, lymph node metastasis, recurrence rate, or DFS. Conclusion In spite of these results, it is worth further investigating the role of pSTAT3 (serine- and tyrosine-pSTAT3) in oral tongue SCC in larger series because preclinical models are increasingly showing that several anticancer strategies would benefit from STAT3 phosphorylation inhibition. PMID:26330924

  17. Diagnostic and Prognostic Significance of Serum and Tissue Galectin 3 Expression in Patients with Carcinoma of the Bladder

    PubMed Central

    Gendy, Hoda El; Madkour, Bothina; Abdelaty, Sara; Essawy, Fayza; Khattab, Dina; Hammam, Olfat; Nour, Hani H.

    2014-01-01

    Background Galectins are group of proteins found in the cytoplasm, nucleus, cell surface and extracellular matrix. Galectin 3 (Gal-3) displays pathological expression in a variety of processes such as tumorigenesis. Patients and Method 70 patients classified into the control group, cystitis group, transitional cell carcinoma group, and squamous cell carcinoma group were enrolled in this study which aimed to detect the serum level and the intensity of tissue expression of Gal-3. Results Both serum level and tissue expression of Gal-3 were statistically higher in bladder cancer patients compared to the other groups. Gal-3 level expression increased from low to high grade urothelial tumors, with a statistically significant increase of its level and expression between muscle invasive and non-muscle invasive Ta urothelial tumors. Conclusion The serum Gal-3 level is sensitive and specific for the diagnosis of bladder cancer. The prognostic significance of tissue expression is to be confirmed. PMID:26195948

  18. Prognostic Significance of NT-proBNP Levels in Patients over 65 Presenting Acute Myocardial Infarction Treated Invasively or Conservatively

    PubMed Central

    Drewniak, Wojciech; Szybka, Wojciech; Bielecki, Dariusz; Malinowski, Michal; Kotlarska, Joanna; Krol-Jaskulska, Agnieszka; Popielarz-Grygalewicz, Agata; Konwicka, Aleksandra; Dąbrowski, Marek

    2015-01-01

    Objectives. Assessment of prognostic significance of NT-proBNP level and the effects of invasive (I) and conservative (C) treatment of acute myocardial infarction (AMI) in patients over 65. Materials and Methods. One-year survival was assessed in 286 consecutive patients with AMI aged 65–100 (79 ± 8) subjected to I or C treatment (136 and 150 individuals), respectively. Results. 245 (85%) patients survived in-hospital stay: 124 (91.1%) received I treatment and 121 (80.6%) received C treatment. Heart failure (HF) was diagnosed in 30 patients receiving I treatment (22.6%) and in 71 subjected to C treatment (47.3%), p < 0,0001. NT-proBNP levels in the latter group were significantly higher than in the 185 patients without HF (12311 ± 13560 pg/mL versus 4773 ± 8807 pg/mL, p < 0.0001). NT-proBNP levels after coronary angioplasty were lower than in patients receiving C treatment (5922 ± 10250 pg/mL versus 8718 ± 12024 pg/mL, p = 0.0002). Left ventricular ejection fraction was significantly higher in I patients than in C patients (47 ± 13% versus 42 ± 11.6%, p = 0.004). During the one-year follow-up, 82.3% of I patients and 61.2% of the C patients survived (p < 0.0003). There was a significantly lower probability of death at NT-proBNP below 8548.5 pg/mL. Conclusions. The NT-proBNP level in the first day of AMI is a good prognosticator. One-year follow-up prognosis for patients who received I treatment in the AMI is better than that for C patients. I patients exhibit superior left ventricular function after angioplasty and in the follow-up. PMID:26539524

  19. TERT Promoter Mutation Status as an Independent Prognostic Factor in Cutaneous Melanoma

    PubMed Central

    Murali, Rajmohan; Puig-Butille, Joan Anton; Schilling, Bastian; Livingstone, Elisabeth; Potrony, Miriam; Carrera, Cristina; Schimming, Tobias; Möller, Inga; Schwamborn, Marion; Sucker, Antje; Hillen, Uwe; Badenas, Celia; Malvehy, Josep; Zimmer, Lisa; Scherag, André; Puig, Susana

    2014-01-01

    Background Recently, TERT promoter mutations were identified at high frequencies in cutaneous melanoma tumor samples and cell lines. The mutations were found to have a UV-signature and to lead to increased TERT gene expression. We analyzed a large cohort of melanoma patients for the presence and distribution of TERT promoter mutations and their association with clinico-pathological characteristics. Methods 410 melanoma tumor samples were analyzed by Sanger sequencing for the presence of TERT promoter mutations. An analysis of associations between mutation status and various clinical and pathologic variables was performed. Results TERT promoter mutations were identified in 154 (43%) of 362 successfully sequenced melanomas. Mutation frequencies varied between melanoma subtype, being most frequent in melanomas arising in nonacral skin (48%) and melanomas with occult primary (50%), and less frequent in mucosal (23%), and acral (19%) melanomas. Mutations carried a UV signature (C>T or CC>TT). The presence of TERT promoter mutations was associated with factors such as BRAF or NRAS mutation (P < .001), histologic type (P = .002), and Breslow thickness (P < .001). TERT promoter mutation was independently associated with poorer overall survival in patients with nonacral cutaneous melanomas (median survival 80 months vs 291 months for wild-type; hazard ratio corrected for other covariates 2.47; 95% confidence interval [CI] = 1.29 to 4.74; P = .006). Conclusions UV-induced TERT promoter mutations are one of the most frequent genetic alterations in melanoma, with frequencies varying depending on melanoma subtype. In nonacral cutaneous melanomas, presence of TERT promoter mutations is independently associated with poor prognosis. PMID:25217772

  20. Prognostic Significance of VEGF after Twenty-Year Follow-up in a Randomized Trial of Fenretinide in Non-Muscle-Invasive Bladder Cancer.

    PubMed

    Puntoni, Matteo; Petrera, Marilena; Campora, Sara; Garrone, Elsa; Defferrari, Carlotta; Torrisi, Rosalba; Johansson, Harriet; Bruno, Silvia; Curotto, Antonio; DeCensi, Andrea

    2016-06-01

    Non-muscle-invasive bladder cancer (NMIBC) may progress to muscle-invasive disease, but no effective preventive treatments are available. In addition, no reliable prognostic biomarkers have been identified. We assessed the long-term effect of the oral retinoid fenretinide and the prognostic value of circulating VEGF levels. We updated through the Tumor Registry the vital status of 99 patients with resected Ta/T1 bladder tumors who were recruited in a randomized trial of 2 years of fenretinide or no treatment in 1993-1994. Serum VEGF levels measured at baseline and 12 months were available in a subgroup of 62 patients. After a median of 20.5 years, 54 subjects died, 35 of any cancer and 14 of bladder cancer. Neither overall survival (OS), nor cancer survival (CS) or bladder cancer survival (BCS) was affected by fenretinide (log-rank P ≥ 0.2). DNA aneuploidy in bladder washing was associated with shorter OS (P = 0.02), CS (P = 0.05), and BCS (P = 0.09). Subjects with baseline VEGF levels in the top quintile (≥350 pg/mL) had a significantly shorter OS (P = 0.01), CS (P = 0.02), and BCS (P = 0.008). The trend across quintiles of VEGF was significant for BCS (P = 0.007). Multivariate analyses showed that, in addition to smoking status, VEGF level in the top quintile was an independent prognostic factor for OS (HR = 2.7; 95% CI, 1.1-6.5), CS (HR = 3.3; 95% CI, 1.1-9.4) and BCS (HR = 8.9; 95% CI,1.3-61). Fenretinide did not affect the long-term outcome of patients with NMIBC. High serum VEGF level was a significant predictor of overall and cancer death and may help to identify high-risk subjects who may benefit from a preventive therapy. Cancer Prev Res; 9(6); 437-44. ©2016 AACR. PMID:27045034

  1. Prognostic Significance of Cyclin D1 Expression in Colorectal Cancer: A Meta-Analysis of Observational Studies

    PubMed Central

    Li, Yang; Wei, Jun; Xu, Chuanhui; Zhao, Zhongxin; You, Tiangeng

    2014-01-01

    Objective Cyclin D1 plays a vital role in cancer cell cycle progression and is overexpressed in many human cancers, including colorectal cancer (CRC). However, the prognostic value of cyclin D1 overexpression in colorectal cancer is conflicting and heterogeneous. We conducted a meta-analysis to more precisely evaluate its prognostic significance. Methods A comprehensive literature search for relevant studies published up to January 2014 was performed using PubMed, EMBASE, and ISI Web of Science. The pooled hazard ratio (HR) with 95% confidence intervals (CI) was used to estimate the effects. Results 22 studies with 4150 CRC patients were selected to evaluate the association between cyclin D1 and overall survival (OS), disease-free survival (DFS) and clinicopathological parameters. In a random-effects model, the results showed that cyclin D1 overexpression in CRC was significantly associated with both poor OS (HR = 0.73, 95% CI: 0.63–0.85, P<0.001) and DFS (HR = 0.60, 95% CI: 0.44–0.82, P = 0.001). Additionally, cyclin D1 overexpression was significantly associated with more relative older patients (≥60 years) (OR 0.62, 95% CI 0.44–0.89, P = 0.009), T3,4 tumor invasion (OR 0.70, 95% CI 0.57–0.85, P<0.001), N positive (OR 0.75, 95% CI 0.60–0.95, P = 0.016) and distant metastasis (OR 0.60, 95% CI 0.36–0.99, P = 0.047) of CRC. Conclusion The meta-analysis results indicated that cyclin D1 is an unfavorable prognostic factor for CRC. Cyclin D1 overexpression might be associated with poor clinical outcome and some clinicopathological factors such as age, T category, N category and distant metastasis in CRC patients. PMID:24728073

  2. Independent Living Resource Manual for American Indians and Alaska Natives with Significant Disabilities.

    ERIC Educational Resources Information Center

    Sanderson, Priscilla Lansing; And Others

    This resource manual for American Indians and Alaska Natives with significant disabilities lists sources of independent living information and resources available within tribal, state, and federal organizations. The first section defines independent living in the context of this population and introduces state level services, mechanisms for…

  3. Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Colorectal Liver Metastasis: A Systematic Review and Meta-Analysis

    PubMed Central

    Zhang, Aiqun; Lu, Wenping; Xiang, Canhong; Dong, Jiahong

    2016-01-01

    Background and Objective Inflammation is deemed to play critical roles in tumor progression and metastasis, and an increased neutrophil-lymphocyte ratio (NLR) has been reported to correlate with poor survivals in various malignancies. However, association between NLR elevation and survival outcome in patients with colorectal liver metastasis (CRLM) remains controversial. The aim of this study was to investigate the prognostic significance of elevated NLR in CRLM. Methods The meta-analysis was conducted in adherence to the MOOSE guidelines. PubMed, Embase, Cochrane Library, Web of Science and the Chinese SinoMed were systematically searched to identify eligible studies from the initiation of the databases to May, 2016. Overall survival (OS) and recurrence free survival (RFS) were pooled by using hazard ratio (HR) with corresponding 95% confidence interval (CI). Correlation between NLR values and clinicopathological features was synthesized by using odds ratio (OR) with corresponding 95% CI. Results A total of 1685 patients from 8 studies (9 cohorts) were analyzed, consisting 347 (20.59%) in high pretreatment NLR value group and 1338 (79.41%) in low pretreatment NLR value one. The results demonstrated that elevated pretreatment NLR was significantly related to poor OS (HR 2.17, 95% CI 1.82–2.58) and RFS (HR 1.96, 95% CI 1.64–2.35) in patients with CRLM. Conclusion The result of this systematic review and meta-analysis indicated that an elevated pretreatment NLR was closely correlated with poor long-term survival (OS and RFS) in CRLM patients. NLR can be routinely monitored and serve as a useful and cost-effective marker with strong prognostic significance in patients with CRLM. PMID:27427969

  4. Prognostic significance of PD-L1 expression in patients with gastric cancer in East Asia: a meta-analysis

    PubMed Central

    Liu, Yong-Xuan; Wang, Xin-Shuai; Wang, Yu-Feng; Hu, Xiao-Chen; Yan, Jun-Qiang; Zhang, Ya-Li; Wang, Wei; Yang, Rui-Jie; Feng, Ying-Ying; Gao, She-Gan; Feng, Xiao-Shan

    2016-01-01

    The overexpression of programmed cell death-ligand 1(PD-L1) has been observed in gastric cancer (GC). However, whether the expression of PD-L1 in tumor cells or blood serum is associated with the prognosis of patients with GC remains unclear. Therefore, we performed a meta-analysis to evaluate the prognostic significance of PD-L1 expression in GC. Electronic databases were searched systematically. Studies that met the inclusion criteria were included in the meta-analysis. Data concerning the hazard ratio (HR) for overall survival and disease-free survival with a 95% confidence interval (CI) according to the expression status of PD-L1 evaluated by immunohistochemistry or enzyme-linked immunosorbent assay were extracted. The data were analyzed using a random effects model. Subgroup analyses were proposed. Our results showed that eight studies with 950 patients met the inclusion criteria and were included in the meta-analysis. The pooled HR for overall survival indicated that patients with PD-L1-positive expression had significantly shorter survival time compared with the PD-L1-negative group (HR 1.60, 95% CI 1.09–2.36, P=0.012). The pooled HR for disease-free survival demonstrated that the difference between the two groups was not statistically significant (HR 1.02, 95% CI 0.32–3.20, P=0.98). In conclusion, our results indicate that the evaluation of PD-L1 overexpression in GC tissue or blood serum may be useful in the future as a novel prognostic factor. PMID:27226727

  5. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide

    PubMed Central

    Verstuyft, Céline; Costedoat-Chalumeau, Nathalie; Hummel, Aurélie; Le Guern, Véronique; Sacré, Karim; Meyer, Olivier; Daugas, Eric; Goujard, Cécile; Sultan, Audrey; Lobbedez, Thierry; Galicier, Lionel; Pourrat, Jacques; Le Hello, Claire; Godin, Michel; Morello, Rémy; Lambert, Marc; Hachulla, Eric; Vanhille, Philippe; Queffeulou, Guillaume; Potier, Jacky; Dion, Jean-Jacques; Bataille, Pierre; Chauveau, Dominique; Moulis, Guillaume; Farge-Bancel, Dominique; Duhaut, Pierre; Saint-Marcoux, Bernadette; Deroux, Alban; Manuzak, Jennifer; Francès, Camille; Aumaitre, Olivier; Bezanahary, Holy; Becquemont, Laurent; Bienvenu, Boris

    2016-01-01

    Objective To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). Methods We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR) was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. Results Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02–24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064–10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. Conclusion This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients. PMID:27002825

  6. Vasculogenic mimicry has no prognostic significance in pT3 and pT4 cutaneous melanoma.

    PubMed

    Massi, Daniela; Franchi, Alessandro; Paglierani, Milena; Ketabchi, Sheyda; Borgognoni, Lorenzo; Reali, Umberto Maria; Santucci, Marco

    2004-04-01

    The concept of vasculogenic mimicry has been introduced to define periodic acid-Schiff (PAS)-positive channels and loops lined by tumor cells, instead of endothelium, able to contribute to microcirculation in uveal melanomas. Previous studies have shown that the PAS-positive patterns are associated with a poor prognosis in uveal melanoma. The aim of the current study was to investigate whether vasculogenic mimicry has a prognostic impact in pT3 and pT4 cutaneous melanoma. Fifteen patients with pT3 and pT4 cutaneous melanoma who did not experience progression after 10 years of follow-up and 30 matched controls who underwent progression were selected. Tumor sections were stained with PAS reaction, omitting the nuclear counterstaining. For immunohistochemistry, sections were stained with CD31, CD105 (endoglin), and laminin. Differences in the distribution of the PAS-positive patterns and a series of clinicopathological variables were evaluated by the Pearson chi(2) and Mann-Whitney U tests. We observed PAS-positive linear sheets, arcs, elliptical loops, and networks encircling roundish to oval aggregates of melanoma cells. The overall distribution of the PAS-positive patterns did not match with the blood microvessels' architecture as detected by immunohistochemical analysis. No statistically significant differences in the distribution of PAS-positive patterns were found between cases and controls. The presence of a parallel pattern correlated significantly with thickness (P = 0.04), whereas an inverse correlation was found with vessel area (P = 0.05). In conclusion, our results suggest that there is a mismatch between vasculogenic mimicry and tumor angiogenesis and do not support any prognostic role of vasculogenic mimicry in thick cutaneous melanoma. PMID:15116332

  7. Predictive and Prognostic Significance of Glutathione Levels and DNA Damage in Cervix Cancer Patients Undergoing Radiotherapy

    SciTech Connect

    Vidyasagar, Mamidipudi Srinivasa; Kodali, Maheedhar; Prakash Saxena, Pu

    2010-10-01

    Purpose: To assess the predictive significance of serum glutathione (GSH) and tumor tissue DNA damage in the treatment of cervical cancer patients undergoing chemoradiotherapy. Methods and Materials: This study included subjects undergoing hysterectomy (for normal cervix tissue) and cervical cancer patients who underwent conventional concurrent chemoradiotherapy (cisplatin once per week for 5 weeks with concurrent external radiotherapy of 2 Gy per fraction for 5 weeks, followed by two applications of intracavitary brachytherapy once per week after 2 weeks' rest). Blood was collected after two fractions, whereas both blood and tissues were collected after five fractions of radiotherapy in separate groups of subjects. Serum for total GSH content and tissues were processed for single-cell gel electrophoresis (SCGE) assay for DNA damage analysis. Clinical tumor radioresponse was assessed 2 months after the completion of treatment as complete responders (CR) (100% shrinkage), partial responders (PR) (>50%), and nonresponders (NR) (<50%). Results: Serum GSH content depleted significantly after a total dose of 4 Gy and 10 Gy of radiotherapy with a single dose of cisplatin, which was significantly lesser in NR than of CR patients. Similarly, Olive Tail Moment, the index of DNA damage, indicated significantly higher values in the fifth fraction of radiotherapy (5-RT) than in pretreatment. The DNA damage after 5-RT in the NR subgroup was significantly lower than that of CR. Conclusions: Serum GSH analysis and tumor tissue SCGE assay found to be useful parameters for predicting chemoradioresponse prior to and also at an early stage of treatment of cervical cancers.

  8. Tumor Necrosis Adds Prognostically Significant Information to Grade in Clear Cell Renal Cell Carcinoma: A Study of 842 Consecutive Cases From a Single Institution.

    PubMed

    Khor, Li-Yan; Dhakal, Hari P; Jia, Xuefei; Reynolds, Jordan P; McKenney, Jesse K; Rini, Brian I; Magi-Galluzzi, Cristina; Przybycin, Christopher G

    2016-09-01

    Tumor necrosis has been shown to be an independent predictor of adverse outcome in renal cell carcinoma. A modification of the International Society of Urological Pathology (ISUP) grading system for renal cell carcinomas has recently been proposed, which incorporates the presence of tumor necrosis into grade. The investigators proposing this system found that necrosis added significant prognostic information to ISUP grade. We attempted to describe our experience with the effect of tumor necrosis in relationship to nuclear grade by reviewing the slides from a large consecutive series of localized clear cell renal cell carcinomas from our institution and obtaining long-term clinical follow-up information (overall survival). Of the 842 clear cell renal cell carcinomas reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and 140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. Five hundred and forty-seven (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%) were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2 months (range 0.12 to 273.6), and 310 (36.8%) patients died. On univariable analysis, there was no significant difference in outcome for tumors of ISUP grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade 4 and necrosis were significant predictors of overall survival on multivariable analysis. When the recently proposed modified grading system incorporating tumor necrosis was applied to our data, there was no significant difference in overall survival between patients with modified grade 1 tumors and those with modified grade 2 tumors (P=0.31); however, there was a statistically significant difference between patients with modified grade 1 or 2 tumors and those with modified grade 3 tumors (P=0.04),and a substantial difference in outcome between those with modified grade 3 and modified grade 4 tumors (P<0.001). When a recursive partitioning approach

  9. MTSS1 is an independent prognostic biomarker for survival in intrahepatic cholangiocarcinoma patients

    PubMed Central

    Shi, Wei; Hasimu, Gulimire; Wang, Yan; Li, Ning; Chen, Mingquan; Zhang, Hao

    2015-01-01

    MTSS1 is a possible metastasis suppressor which has been proved to play a key role in metastasis of various tumors, yet its role in intrahepatic cholangiocarcinoma (ICC) remains unclear. In present study, we reported detection of MTSS1 expression in ICC and explored its clinical significances. Tissue microarrays containing 93 cases with ICC were constructed and immunohistochemistry was performed to detect MTSS1 expression on these arrays. PcDNA3.1-MTSS1 was transfected into QBC939 cell lines and cell function was measured by transwell assay. Data showed that MTSS1 expression was barely detectable in 56 cases (60.0%) of the 93 primary tumors and that lacking MTSS1 expression was significantly associated with tumor size, nodal metastases and advanced disease stage. In addition, survival analysis demonstrated that lacking MTSS1 expression also correlated significantly with tumor recurrence and poor outcome of patients with ICC. Meanwhile, enhanced expression of MTSS1 leaded to inhibition of the migration of QBC939 cell lines in vitro. These findings together support that MTSS1 may serve as a useful biomarker in predicting tumor recurrence and prognosis of ICC. PMID:26692940

  10. Investigation of prognostic significance of CD109 expression in women with vulvar squamous cell carcinoma

    PubMed Central

    Özbay, Pelin Özün; Ekinci, Tekin; Yiǧit, Seyran; Yavuzcan, Ali; Uysal, Selda; Soylu, Ferit; Cakalagaoglu, Fulya

    2013-01-01

    Objective The goal of this study was to investigate the between cluster of differentiation 109 (CD109) expression and tumor diameter, invasion depth, tumor grade, presence of lymph-node metastasis, and overall survival in patients with vulvar squamous cell carcinoma, which is the most common type of vulvar cancer. Method Twenty-six patients who underwent an operation for vulvar cancer between 1999 and 2009 in our clinic were included in this study. Immunohistochemical staining was performed on formalin-fixed and paraffin-embedded tissue. Result Tumor diameter was not found to be significantly associated with CD109 expression, intensity of cytoplasmic staining, or combined score (P = 0.325, P = 0.169, P = 0.352, respectively). Invasion depth and combined score were also not significantly correlated with CD109 expression (P = 0.324 and P = 0.174 respectively). There was a negative correlation between invasion depth and the intensity of cytoplasmic staining (P = 0.042). There was no significant correlation between tumor stage and CD109 expression, the intensity of cytoplasmic staining, and the combined score (P = 0.574, P = 0.389, P = 0.605, respectively). A significant positive correlation was observed between tumor grade and CD109 expression, the intensity of cytoplasmic staining, and the combined score (P = 0.003, P = 0.018, P = 0.008, respectively). No significant difference was found between the percentages of CD109 expression in patients with positive (48%) and negative (11%) lymph nodes (P = 0.058). The percentage of CD109 expression did not significantly differ in relation to overall survival (P = 0.483). Conclusion Comprehensive and more extensive studies are needed to examine the relationship between CD109 expression and vulvar malignant lesions. PMID:23776335

  11. miR-517a is an independent prognostic marker and contributes to cell migration and invasion in human colorectal cancer

    PubMed Central

    MA, WENQI; YU, QIANG; JIANG, JUE; DU, XIAOPENG; HUANG, LILI; ZHAO, LINLIN; ZHOU, QI

    2016-01-01

    Colorectal cancer (CRC) is a highly invasive tumor that is frequently associated with distant metastasis, which is the primary cause of poor prognosis. However, the mechanisms of metastasis remain poorly understood. MicroRNAs (miRNAs/miRs) have been considered to be implicated in CRC progression. In particular, miR-517a is proposed as a novel tumor-associated miRNA and has a potential role in tumor metastasis. The expression of miR-517a in CRC specimens was detected by reverse transcription-quantitative polymerase chain reaction. Transwell assays were performed to determine the migration and invasion of CRC cells. The putative target genes of miR-517a were disclosed using publicly available databases and western blot analysis. The present study identified that the expression of miR-517a was significantly higher in CRC tissues as compared with adjacent non-tumor tissues. Clinical analysis indicated that increased expression of miR-517a was correlated with poor prognostic features and poor long-term survival of CRC patients. In vitro evidences demonstrated that downregulation of miR-517a inhibited cell migration and invasion in HCT-116 cells. By contrast, upregulation of miR-517a increased the number of migrated and invaded SW480 cells. Notably, miR-517a expression was inversely regulated by forkhead box J3 (FOXJ3) abundance in CRC cells. Furthermore, an inverse correlation between miR-517a and FOXJ3 expression was observed in CRC tissues. In conclusion, miR-517a appears to be an independent prognostic marker for predicting survival of CRC patients, and may promote cell migration and invasion by inhibiting FOXJ3. PMID:27073521

  12. Prognostic significance of exercise blood pressure and heart rate in middle-aged men.

    PubMed

    Filipovský, J; Ducimetière, P; Safar, M E

    1992-09-01

    Systolic blood pressure and heart rate measured at rest and during a standardized exercise test were analyzed in the cohort of middle-aged male employees followed-up an average of 17 years in the Paris Prospective Study I. The population sample selected for the analysis included 4,907 men who completed at least 5 minutes of bicycle ergometry, who had no heart disease at entry, and whose resting blood pressure was less than or equal to 180/105 mm Hg. Exercise-induced increase in systolic blood pressure was positively correlated with resting systolic blood pressure (r = 0.104, p less than 0.0001), whereas the correlation of exercise-induced heart rate increase with resting heart rate was negative (r = -0.169, p less than 0.001). Using Cox regression analysis with the inclusion of resting systolic blood pressure and heart rate; exercise-induced elevations of systolic blood pressure and heart rate; and controlling for age, smoking, total cholesterol, body mass index, electrical left ventricular hypertrophy, and sports activities, cardiovascular mortality was found to be associated with the systolic blood pressure increase (p less than 0.05), whereas no association with resting systolic blood pressure was found. Total mortality was predicted by resting systolic blood pressure and its elevation (p less than 0.01 for both) and by resting heart rate (p less than 0.0001). The heart rate increase did not contribute to death prediction. In conclusion, the magnitude of the exercise-induced increase of systolic blood pressure, but not of heart rate, may represent a risk factor for death from cardiovascular as well as noncardiovascular causes, independently of resting blood pressure and heart rate. PMID:1387630

  13. Prognostic significance of neurological signs in high-risk infants - a systematic review.

    PubMed

    Hamer, Elisa G; Hadders-Algra, Mijna

    2016-03-01

    The aim of this paper was to systematically review the literature on the significance of specific neurological signs in infancy, in particular in infants at risk for developmental problems such as cerebral palsy (CP). A literature search was performed using the databases PubMed, Embase, Web of Science, and AMED. Papers on infantile reactions ('primitive reflexes') and postural reactions were included if data were available allowing for calculation of sensitivity, specificity, or positive and negative predictive value for CP or atypical developmental outcome. Our search identified 23 articles on 20 different neurological signs. Properties of six neurological signs were reported in at least three different papers. The data indicated that, in early infancy, an absent Moro or plantar grasp response may be predictive for adverse developmental outcome. After early infancy, persistence of the Moro response and asymmetric tonic neck reflex was clinically significant. Prediction of a delayed emergence of the parachute reaction increases with age. Abnormal performances on the pull-to-sit manoeuvre and vertical suspension test have predictive significance throughout infancy. The neurological signs reviewed have some predictive value in infants at risk. For most of the signs, criteria for abnormality and significance are age-dependent. PMID:27027608

  14. Study of prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves

    PubMed Central

    Bhadoo, Divya; Bajpai, M.; Abid, Ali; Sukanya, Gayan; Agarwala, Sandeep; Srinivas, M.; Deka, Deepika; Agarwal, Nutan; Agarwal, Ramesh; Kumar, Rakesh

    2015-01-01

    Aims: Study on prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves. Materials and Methods: Antenatally diagnosed hydronephrosis patients were included. Postnatally, they were divided into two groups, posterior urethral valve (PUV) and non-PUV. The studied parameters were: Gestational age at detection, surgical intervention, ultrasound findings, cord blood and follow up plasma renin activity (PRA) values, vesico-ureteric reflux (VUR), renal scars, and glomerular filtration rate (GFR). Results: A total of 25 patients were included, 10 PUV and 15 non-PUV. All infants with PUV underwent primary valve incision. GFR was less than 60 ml/min/1.73 m2 body surface area in 4 patients at last follow-up. Keyhole sign, oligoamnios, absent bladder cycling, and cortical cysts were not consistent findings on antenatal ultrasound in PUV. Cord blood PRA was significantly higher (P < 0.0001) in PUV compared to non-PUV patients. Gestational age at detection of hydronephrosis, cortical cysts, bladder wall thickness, and amniotic fluid index were not significantly correlated with GFR while PRA could differentiate between poor and better prognosis cases with PUV. Conclusions: Ultrasound was neither uniformly useful in diagnosing PUV antenatally, nor differentiating it from cases with non-PUV hydronephrosis. In congenital hydronephrosis, cord blood PRA was significantly higher in cases with PUV compared to non-PUV cases and fell significantly after valve ablation. Cord blood PRA could distinguish between poor and better prognosis cases with PUV. PMID:25829668

  15. Diagnostic and prognostic significance of serum microRNAs in colorectal cancer.

    PubMed

    Menéndez, Pablo; Villarejo, Pedro; Padilla, David; Menéndez, José M; Montes, Jose A Rodríguez

    2013-02-01

    MicroRNAs are short non-coding RNA molecules involved in the regulation of gene expression. There are few studies related to the determination of serum microRNAs in colorectal cancer. The identification of microRNAs in peripheral blood as noninvasive markers of tumor disease may lead to potential applications, although further clinical studies focusing on serum microRNAs are required to determine their clinical significance for the diagnosis and prognosis outcome of colorectal cancer. PMID:22903548

  16. Thyroid Gland Involvement in Carcinoma Larynx and Hypopharynx-Predictive Factors and Prognostic Significance

    PubMed Central

    Iype, Elizabeth Mathew; Jagad, Vijay; Varghese, Bipin T.; Sebastian, Paul

    2016-01-01

    Introduction Intraoperative management of thyroid gland in laryngeal and hypopharyngeal cancer is controversial. Aim The objectives of this study were to determine the incidence of thyroid gland invasion in patients undergoing surgery for laryngeal or hypopharyngeal carcinoma, to assess predictive factors and to assess the prognosis in patients with and without thyroid gland invasion. Materials and Methods One hundred and thirty-three patients who underwent surgery for carcinoma larynx and hypopharynx from 2006 to 2010 were reviewed retrospectively. Surgical specimens were examined to determine the incidence of thyroid gland invasion and predictive factors were analysed. The recurrence rate and the survival in patients with and without thyroid gland invasion were also analysed. Results Out of the 133 patients with carcinoma larynx and hypopharynx who underwent surgery, histological thyroid gland invasion was observed in 28/133 (21%) patients. Significant relationship was found between histological thyroid gland invasion and preoperative evidence of thyroid cartilage erosion by CT scan and also when gross thyroid gland involvement observed during surgery. There is significant association between thyroid gland invasion when there is upper oesophageal or subglottic involvement. Conclusion After analysing the retrospective data from our study, we would like to suggest that thyroid gland need not be removed routinely in all laryngectomies, unless there is advanced disease with thyroid cartilage erosion and gross thyroid gland involvement or disease with significant subglottic or oesophageal involvement. PMID:27042568

  17. Prognostic Significance of Microvessel Density Determining by Endoglin in Stage II Rectal Carcinoma: A Retrospective Analysis

    PubMed Central

    Martinovic, Zeljko; Kovac, Drazen; Martinovic, Mia

    2015-01-01

    Background. The role of endoglin in the Dukes B rectal cancer is still unexplored. The aim of this study was to examine the expression of endoglin (CD105) in resected rectal cancer and to evaluate the relationship between microvessels density (MVD), clinicopathological factors, and survival rates. Methods. The study included 95 primary rectal adenocarcinomas, corresponding to 67 adjacent and 73 distant normal mucosa specimens from surgical resection samples. Tumor specimens were paraffin-embedded and immunohistochemical staining for the CD105 endothelial antigen was performed to count CD105-MVD. For exact measurement of the CD105-MVD used a computer-integrated system Alphelys Spot Browser 2 was used. Results. The intratumoral CD105-MVD was significantly higher compared with corresponding adjacent mucosa (P < 0.0001) and distant mucosa specimens (P < 0.0001). There was no significant difference in the CD105-MVD according to patients age, gender, tumor location, grade of differentiation, histological type, depth of tumor invasion, and tumor size. The overall survival rate was significantly higher in the low CD105-MVD group of patients than in the high CD105-MVD group of patients (log-rank test, P = 0.0406). Conclusion. CD105-assessed MVD could help to identify patients with possibility of poor survival in the group of stage II RC. PMID:26089870

  18. Prognostic Significance of N-Glycolyl GM3 Ganglioside Expression in Non-Small Cell Lung Carcinoma Patients: New Evidences.

    PubMed

    Blanco, Rancés; Domínguez, Elizabeth; Morales, Orlando; Blanco, Damián; Martínez, Darel; Rengifo, Charles E; Viada, Carmen; Cedeño, Mercedes; Rengifo, Enrique; Carr, Adriana

    2015-01-01

    The prognostic role of N-glycolyl GM3 ganglioside (NeuGcGM3) expression in non-small cell lung carcinoma (NSCLC) still remains controversial. In this study, the NeuGcGM3 expression was reevaluated using an increased number of NSCLC cases and the 14F7 Mab (a highly specific IgG1 raised against NeuGcGM3). An immunohistochemical score integrating the percentage of 14F7-positive cells and the intensity of reaction was applied to reassess the relationship between NeuGcGM3 expression, some clinicopathological features, and the overall survival (OS) of NSCLC patients. The double and the triple expression of NeuGcGM3 with the epidermal growth factor receptor (EGFR) and/or its ligand, the epidermal growth factor (EGF), were also evaluated. NeuGcGM3 expression correlates with both S-Phase fraction (p = 0.006) and proliferation index (p = 0.000). Additionally, NeuGcGM3 expression was associated with a poor OS of patients in both univariate (p = 0.020) and multivariate (p = 0.010) analysis. Moreover, the double and/or the triple positivity of tumors to NeuGcGM3, EGFR, and/or EGF permitted us to identify phenotypes of NSCLC with a more aggressive biological behavior. Our results are in agreement with the negative prognostic significance of NeuGcGM3 expression in NSCLC patients. However, standardization of techniques to determine the expression of NeuGcGM3 in NSCLC as well as the implementation of a universal scoring system is recommended. PMID:26634172

  19. Prognostic Significance of N-Glycolyl GM3 Ganglioside Expression in Non-Small Cell Lung Carcinoma Patients: New Evidences

    PubMed Central

    Blanco, Rancés; Domínguez, Elizabeth; Morales, Orlando; Blanco, Damián; Martínez, Darel; Rengifo, Charles E.; Viada, Carmen; Cedeño, Mercedes; Rengifo, Enrique; Carr, Adriana

    2015-01-01

    The prognostic role of N-glycolyl GM3 ganglioside (NeuGcGM3) expression in non-small cell lung carcinoma (NSCLC) still remains controversial. In this study, the NeuGcGM3 expression was reevaluated using an increased number of NSCLC cases and the 14F7 Mab (a highly specific IgG1 raised against NeuGcGM3). An immunohistochemical score integrating the percentage of 14F7-positive cells and the intensity of reaction was applied to reassess the relationship between NeuGcGM3 expression, some clinicopathological features, and the overall survival (OS) of NSCLC patients. The double and the triple expression of NeuGcGM3 with the epidermal growth factor receptor (EGFR) and/or its ligand, the epidermal growth factor (EGF), were also evaluated. NeuGcGM3 expression correlates with both S-Phase fraction (p = 0.006) and proliferation index (p = 0.000). Additionally, NeuGcGM3 expression was associated with a poor OS of patients in both univariate (p = 0.020) and multivariate (p = 0.010) analysis. Moreover, the double and/or the triple positivity of tumors to NeuGcGM3, EGFR, and/or EGF permitted us to identify phenotypes of NSCLC with a more aggressive biological behavior. Our results are in agreement with the negative prognostic significance of NeuGcGM3 expression in NSCLC patients. However, standardization of techniques to determine the expression of NeuGcGM3 in NSCLC as well as the implementation of a universal scoring system is recommended. PMID:26634172

  20. Opposite Prognostic Significance of Cellular and Serum Circulating MicroRNA-150 in Patients with Chronic Lymphocytic Leukemia

    PubMed Central

    Stamatopoulos, Basile; Van Damme, Michaël; Crompot, Emerence; Dessars, Barbara; Housni, Hakim El; Mineur, Philippe; Meuleman, Nathalie; Bron, Dominique; Lagneaux, Laurence

    2015-01-01

    MicroRNAs (or miRs) play a crucial role in chronic lymphocytic leukemia (CLL) physiopathology and prognosis. In addition, circulating microRNAs in body fluids have been proposed as new biomarkers. We investigated the expression of matched cellular and serum circulating microRNA-150 by quantitative real-time PCR (qPCR) from purified CD19+ cells or from CLL serums obtained at diagnosis in a cohort of 273/252 CLL patients with a median follow-up of 78 months (range 7–380) and correlated it to other biological or clinical parameters. We showed that miR-150 was significantly overexpressed in CLL cells/serums compared with healthy subjects (P < 0.0001). Among CLL patients, a low cellular miR-150 expression level was associated with tumor burden, disease aggressiveness and poor prognostic factors. In contrast, a high level of serum miR-150 was associated with tumor burden markers and some markers of poor prognosis. Similarly, cellular and serum miR-150 also predicted treatment-free survival (TFS) and overall survival (OS) in an opposite manner: patients with low cellular/serum miR-150 levels have median TFS of 40/111 months compared with high-level patients who have a median TFS of 122/60 months (P < 0.0001/P = 0.0066). Similar results were observed for OS. We also found that cellular and serum miR-150 levels vary in an opposite manner during disease progression and that cellular miR-150 could be regulated by its release into the extracellular space. Cellular and serum levels of miR-150 are associated with opposite clinical prognoses and could be used to molecularly monitor disease evolution as a new prognostic factor in CLL. PMID:25584781

  1. Prognostic significance of the TREK-1 K2P potassium channels in prostate cancer

    PubMed Central

    Zhang, Gui-Ming; Wan, Fang-Ning; Qin, Xiao-Jian; Cao, Da-Long; Zhang, Hai-Liang; Zhu, Yao; Dai, Bo; Shi, Guo-Hai; Ye, Ding-Wei

    2015-01-01

    Background TREK-1 channels belong to the two-pore domain potassium channel superfamily and play an important role in central nervous system diseases. However, few studies have examined their role in carcinogenesis. Methods In this study, we assessed the expression of TREK-1 in 100 prostate cancer (PCa) tissues using immunohistochemistry and further analyzed its clinicopathological significance. Next, cell proliferation and cell cycle analysis were carried out on human PCa PC-3 cell lines where TREK-1 was stably knockdown. Results We found that compared with normal prostate tissues, PCa tissues showed overexpressed TREK-1 levels and TREK-1 levels were positively associated with Gleason score and T staging. High level of TREK-1 expression was related to shorter castration resistance free survival (CRFS). Furthermore, knockdown of TREK-1 significantly inhibited PCa cell proliferation in vitro and in vivo, and induced a G1/S cell cycle arrest. Conclusion Our results suggest that TREK-1 might be a biomarker in CRFS judgment of PCa, as well as a potential therapeutic target. PMID:25962960

  2. Prognostic significance of dilated inferior vena cava in advanced decompensated heart failure.

    PubMed

    Lee, Hsin-Fu; Hsu, Lung-An; Chang, Chi-Jen; Chan, Yi-Hsin; Wang, Chun-Li; Ho, Wan-Jing; Chu, Pao-Hsien

    2014-10-01

    Dilated inferior vena cava (IVC) is prevalent among patients with heart failure (HF), but whether its presence predicts worsening renal function (WRF) or adverse outcomes is unclear. This cohort study analyzed patients with left ventricular ejection fraction <40 % and repeated hospitalizations (≥2 times) for HF between August 2009 and August 2011. The study endpoints were death and HF re-hospitalization. Among baseline parameters, IVC diameter was the most powerful predictor for the development of WRF (area under the curve = 0.795, cut-off value = 20.5 mm). During the 2-year follow-up, 36 patients (49 %) were re-hospitalized for HF and 14 patients (19 %) died. The event rates were significantly greater in the WRF group than in the non-WRF group (71 vs. 30 %, P < 0.001 for HF re-hospitalization; 29 vs. 10 %, P = 0.03 for death). In Cox regression model, the risk of combined end-points was increased in patients with aging, elevated blood urine nitrogen, IVC >21 mm, and WRF. When adjusted for confounding factors, IVC >21 mm [hazard ratio (HR) 3.73, 95 % confidence interval (CI) 1.66-8.34] and WRF (HR 2.68, 95 % CI 1.07-6.75) were significant predictors for adverse outcomes. In patients with advanced decompensated HF, dilated IVC (>21 mm) predicted the development of WRF and could be a predictor for adverse outcomes. PMID:24939288

  3. Initial respiratory status in hyperleukocytic acute myeloid leukemia: prognostic significance and effect of leukapheresis.

    PubMed

    Van de Louw, Andry; Schneider, Coursen W; Desai, Ruchi J; Claxton, David F

    2016-06-01

    This study investigated whether initial respiratory status in hyperleukocytic acute myeloid leukemia (AML), as defined by oxygen/ventilatory support, is (1) associated with early mortality and overall survival and (2) improved after leukapheresis. A retrospective chart review of 89 patients requiring leukapheresis was performed. White blood cell count (WBC) decreased from 153 (56-475) × 10(9)/L to 60 (17-259) × 10(9)/L after first leukapheresis (p < 0.01). Initial respiratory status was room air (n = 40), low (n = 31) or high flow oxygen therapy (n = 8) or mechanical ventilation (n = 10). As compared to admission, respiratory status significantly deteriorated after both first and second leukapheresis (p < 0.01) and was not different at day 5 for patients still alive (p = 0.131). Both day 28 mortality and overall survival were significantly affected by initial respiratory status (p < 0.01). Despite being effective in reducing WBC, leukapheresis did not improve respiratory status of hyperleukocytic AML patients, a factor strongly associated with survival. PMID:26374497

  4. The Prognostic Significance of Src and p-Src Expression in Patients with Osteosarcoma

    PubMed Central

    Hu, Chao; Deng, Zhouming; Zhang, Yi; Yan, Lei; Cai, Lin; Lei, Jun; Xie, Yuanlong

    2015-01-01

    Background The expression of Src and phospho-Src (p-Src) is closely related to tumor invasion and metastasis. The aim of the present study was to investigate the expression of these molecules in osteosarcoma and their relationship with each other, to provide a theoretical basis to understand the prognosis of osteosarcoma. Material/Methods We selected surgically resected osteosarcoma specimens from 116 patients of Zhongnan Hospital of Wuhan University and Hubei Cancer Hospital, Hubei, China, between January 2000 and January 2010 with detailed follow-up data. Twenty osteochondroma specimens from the corresponding period were used as controls. Expression of Src and p-Src was detected in osteosarcoma and osteochondroma by immunohistochemistry. We analyzed the relationship of the 2 proteins and osteosarcoma patient prognosis. Results The expression of Src and p-Src in osteosarcoma was significantly higher than the expression level in osteochondroma (P<0.05). The expression levels of the 2 proteins, clinical stage, and tumor metastasis were significantly associated with survival time (P<0.05), but there was no correlation between age or sex and survival time. The expression of Src and p-Src in osteosarcoma was positively correlated. Conclusions Src and p-Src can be used as an auxiliary indicator to determine a malignant phenotype of bone tumors, and the combined detection of Src and p-Src may indicate the prognosis of osteosarcoma. PMID:25725252

  5. Prognostic significance of glutathione S-transferase-pi in invasive breast cancer.

    PubMed

    Huang, Jingxiang; Tan, Puay-Hoon; Thiyagarajan, Jayabaskar; Bay, Boon-Huat

    2003-06-01

    Glutathione S-transferase pi (GST-pi), a Phase II detoxification enzyme, has recently been implicated in protection against apoptosis. Expression of GST-pi and Bcl-2 protein, an established apoptosis marker, was analyzed by immunohistochemistry in 116 cases of infiltrative ductal breast carcinomas in Singapore women. The markers were correlated with apoptosis detected by the TUNEL method and clinico-pathological parameters. There were 67 (58%) GST-pi-positive breast tumors and 43 (37%) Bcl-2-positive tumors. In a large proportion of GST-pi-positive/Bcl-2-positive tumors, there was a distinct accumulation of the GST-pi enzyme within the nucleus of cancer cells when examined by double immunofluorescence labeling under confocal microscopy. GST-pi immunoreactivity was not significantly correlated with any of the traditional histologic factors known to influence prognosis, whereas Bcl-2 overexpression was associated with reduced size of primary tumor (P =.021) and positive estrogen receptor status (P =.001). Univariate analysis revealed that GST-pi-positive, Bcl-2-positive, and lower histological grade tumors had decreased levels of apoptosis (P =.024, P =.011, and P =.029, respectively). However, multivariate analysis showed that histological grade and Bcl-2, but not GST-pi, immunoreactivity were correlated with apoptotic status. The Kaplan-Meier disease-free survival curves showed a significant difference between GST-pi-positive and GST-pi-negative breast cancer cases (P =.002). Disease-free survival in patients with GST-pi-positive tumors was also worse than that in patients with GST-pi-negative tumors in the group who had adjuvant chemotherapy (P =.04). In patients who were lymph node positive, GST-pi immunopositivity was found to influence disease-free survival. Recurrence of tumors was also significantly affected by GST-pi immunoreactivity (relative risk of 8.1). The findings indicate that GST-pi-positive tumors are more aggressive and have a poorer prognosis than

  6. Prognostic significance of tissue and serum HER2 and MUC1 in canine mammary cancer.

    PubMed

    Campos, Liliane C; Silva, Juliana O; Santos, Fabiana S; Araújo, Marina R; Lavalle, Gleidice E; Ferreira, Enio; Cassali, Geovanni D

    2015-07-01

    The aim of our study was to compare serum levels and protein tissue of human epidermal growth factor receptor-2 proto-oncogene (HER2) and mucin 1 (MUC1) using an antigen-capture enzyme-linked immunosorbent assay and immunohistochemistry (IHC) in canine mammary carcinomas and investigate how the 2 markers correlate with dogs with metastasis and without metastasis to a regional lymph node. Forty-eight female dogs were selected, including 14 with non-metastatic cancer, 14 with lymph node metastasis, and 20 healthy animals. Serum samples were collected from all the animals and tissues from 28 dogs with malignant mammary tumor with or without metastasis for evaluated HER2 and MUC1 expression. Tissue sample were evaluated for MUC1 and HER2 immunoexpression by IHC. The results showed measurable serum levels of MUC1 and HER2 in all groups. While serum MUC1 levels were significantly higher in animals with metastasis than the other 2 groups, no increase was observed in HER2 serum levels. The MUC1 IHC results showed that only membrane immunostaining was significantly different between the groups. Statistically, there was an association between immunostaining and the serum HER2 levels. Our results indicate that serum concentrations of HER2 and the IHC staining pattern for HER2 in primary tumor do not correlate with the presence of regional metastasis. However, increased concentrations of MUC1 in the serum of dogs with mammary cancer are associated with the presence of metastasis to regional lymph nodes. A membrane pattern of IHC staining for MUC1 in the primary tumor suggests that metastases to regional lymph node are present. PMID:26179096

  7. Prognostic significance of resting anterior thallium-201 defects in patients with inferior myocardial infarction

    SciTech Connect

    Gibson, R.S.; Taylor, G.J.; Watson, D.D.; Berger, B.C.; Crampton, R.S.; Martin, R.P.; Beller, G.A.

    1980-11-01

    To determine whether Tl-201 scintigraphy performed at rest during the late hospital phase of inferior myocardial infarction can predict subsequent coronary events, 25 patients with historical, enzymatic, and electrocardiographic criteria of transmural inferior infarction underwent serial imaging with computer quantification 7 to 35 days after admission. All 25 patients had inferior defects, and 13 (52%) also had anterior defects implying stenosis of the left anterior descending coronary artery. The patients were divided into those with inferior and anterior perfusion defects (Group 1) and those with inferior defects alone (Group 2). In Group 1, three patients had persistent defects in the anterior wall and ten had initial defects with redistribution. New or recurrent coronary events - which included new onset or progression of angina pectoris, sudden death, reinfarction, and congestive heart failure - were recorded over an average 7.2 months of followup (range 3 to 9 mo) for all patients. Ten of 13 (77%) patients in Group 1 had 17 coronary events and four of 12 (33%) patients in Group 2 had six coronary events (p < 0.02). Nine patients in Group 1 and three in Group 2 developed angina (p < 0.03). The apparently increased prevalence in Group 1 of sudden death (8% against 0%), reinfarction (8% against 0%), and congestive heart failure (46% against 25%) was not statistically significant. Thus resting T1-201 scintigraphy with computer quantification is a highly sensitive method to detect inferior myocardial infarction even in the late hospital phase. Moreover, it appears to identify those patients with inferior infarction at high risk for subsequent coronary events, presumably due to stenosis of the left anterior descending coronary artery.

  8. Clinical and prognostic significance of lung thallium uptake on rest imaging in acute myocardial infarction

    SciTech Connect

    Jain, D.; Lahiri, A.; Raftery, E.B. )

    1990-01-15

    Exercise-induced pulmonary uptake of thallium-201 in patients with ischemic heart disease is probably due to transient pulmonary edema and left ventricular failure induced by exercise. The significance of increased lung uptake of thallium-201 at rest after acute myocardial infarction (AMI) has not been described. Ninety-six patients admitted with chest pain for suspected AMI or unstable angina underwent thallium-201 imaging at rest. Using conventional diagnostic criteria, 62 had AMI, 12 had unstable angina and 22 had neither. Increased lung uptake of thallium-201 was present in 24 of the total 96 (25%) patients, 20 of the 62 (32%) patients with AMI and 4 of 34 (13%) patients with no evidence of infarction. In the AMI group, those with increased lung thallium-201 uptake had a higher mean +/- standard deviation segmental thallium-201 defect score (22 +/- 7 vs 12 +/- 8, p less than 0.0001), lower ejection fraction (35 +/- 14 vs 49 +/- 14%, p less than 0.002), higher peak creatine kinase levels (2,410 +/- 1,247 vs 1,496 +/- 1,228 IU/liter, p less than 0.01), higher wall motion abnormality score (25 +/- 13 vs 13 +/- 12, p less than 0.0001), increased incidence of clinical in-hospital heart failure (15 of 20 vs 7 of 42, p less than 0.0001) and higher short-term mortality (4 of 20 vs 1 of 42, p less than 0.02) compared to those without increased lung thallium-201 uptake.

  9. Abnormal deposition of collagen/elastic vascular fibres and prognostic significance in idiopathic interstitial pneumonias

    PubMed Central

    Parra, Edwin Roger; Kairalla, Ronaldo Adib; de Carvalho, Carlos Roberto Ribeiro; Capelozzi, Vera Luiza

    2007-01-01

    Background Vascular remodelling has recently been shown to be a promising pathogenetic indicator in idiopathic interstitial pneumonias (IIPs). Aim To validate the importance of the collagen/elastic system in vascular remodelling and to study the relationships between the collagen/elastic system, survival and the major histological patterns of IIPs. Methods Collagen/elastic system fibres were studied in 25 patients with acute interstitial pneumonia/diffuse alveolar damage, 22 with non‐specific interstitial pneumonia/non‐specific interstitial pneumonia and 55 with idiopathic pulmonary fibrosis/usual interstitial pneumonia. The Picrosirius polarisation method and Weigert's resorcin–fuchsin histochemistry and morphometric analysis were used to evaluate the amount of vascular collagen/elastic system fibres and their association with the histological pattern of IIPs. The association between vascular remodelling and the degree of parenchymal fibrosis in usual interstitial pneumonia (UIP) was also considered. Results The vascular measurement of collagen/elastic fibres was significantly higher in UIP than in the lungs of controls, and in those with diffuse alveolar damage and those with non‐specific interstitial pneumonia. In addition, the increment of collagen/elastic fibres in UIP varied according to the degree and activity of the parenchymal fibrosis. The most important predictors of survival in UIP were vascular remodelling classification and vascular collagen deposition. Conclusion A progressive vascular fibroelastosis occurs in IIP histological patterns, probably indicating evolutionarily adapted responses to parenchymal injury. The vascular remodelling classification and the increase in vascular collagen were related to survival in IIP and possibly play a role in its pathogenesis. Further studies are needed to determine whether this relationship is causal or consequential. PMID:17251318

  10. Galectin-1 Is an Independent Prognostic Factor for Local Recurrence and Survival After Definitive Radiation Therapy for Patients With Squamous Cell Carcinoma of the Uterine Cervix

    SciTech Connect

    Huang, Eng-Yen; Chanchien, Chan-Chao; Lin, Hao; Wang, Chung-Chi; Wang, Chong-Jong; Huang, Chao-Cheng

    2013-12-01

    Purpose: To investigate the role of galectin-1 in patients with cervical cancer after definitive radiation therapy. Methods and Materials: We reviewed 154 patients with International Federation of Gynecology and Obstetrics stage I-II squamous cell carcinoma. Patients underwent curative-intent radiation therapy. Paraffin-embedded tissues were analyzed using immunohistochemistry staining for galectin-1. The rates of cancer-specific survival (CSS), local recurrence (LR), and distant metastasis were compared among patient tissue samples with no, weak, and strong galectin-1 expression. The Kaplan-Meier method and the Cox proportional hazard model with hazard ratios and 95% confidence intervals (CIs) were used for univariate and multivariate analyses, respectively. Results: The areas under the curve for the intracellular expression scores of galectin-1 for both LR and CSS were significantly higher than those for stromal expression. There were no significant differences in the demographic data, such as stage and serum tumor markers, between patients with and without intracellular expression of galectin-1 in cancer tissue samples. Using multivariate analyses, the hazard ratios of LR and CSS were 2.60 (95% CI 1.50-4.52) (P=.001) and 1.94 (95% CI 1.18-3.19) (P=.010), respectively. Conclusion: Galectin-1 is an independent prognostic factor associated with LR and CSS in stage I-II cervical cancer patients undergoing definitive radiation therapy. Further studies targeting galectin-1 may improve the local control of cervical cancer.

  11. Diagnostic and prognostic significance of genetic regional heterogeneity in meningiomas1

    PubMed Central

    Pfisterer, Wolfgang K.; Hank, Nicole C.; Preul, Mark C.; Hendricks, William P.; Pueschel, Jeanette; Coons, Stephen W.; Scheck, Adrienne C.

    2004-01-01

    We analyzed the frequency and regional distribution of cells with genetic abnormalities of chromosomes 1, 14, and 22 in meningiomas. This data was evaluated for correlation to the clinical outcome of the patients. Eight defined areas of each of 77 paraffin-embedded meningioma samples (59 grade I, 13 grade II, and 5 grade III) were analyzed by fluorescent in situ hybridization using bacterial artificial chromosome probes localized to chromosomes 1p36.32, 1q25.3, 14q13.3, 14q32.12, 22q11.2, and 22q12.1-3. Chromosome deletion was considered to be regionally heterogeneous if <7 regions showed cells with chromosome deletions. Deletion of 1p occurred in 35% of the grade I tumors. Distribution of cells with 1p deletion was regionally heterogeneous in 25% and homogeneous in 10% of grade I tumors. Distribution of cells with deletion of 1p was regionally heterogeneous in 23% and homogeneous in 69% of the grade II tumors. All grade III meningiomas had homogeneous distribution of cells with deletion of chromosome 1p. Distribution of cells with deletion of 14q was regionally heterogeneous in 27% and homogeneous in 2% of the grade I meningiomas, heterogeneous in 31% and homogeneous in 62% of the grade II tumors, and heterogeneous in 40% and homogeneous in 60% of the grade III meningiomas. Distribution of cells with deletion of 22q was regionally heterogeneous in 15% and homogeneous in 3% of the grade I tumors, heterogeneous in 15% and homogeneous in 31% of grade II tumors, and homogeneous in 20% of the grade III meningiomas. Distribution of cells with trisomy 22q was regionally heterogeneous in 10% of grade I tumors, heterogeneous in 23% of grade II, and homogeneous in 80% of grade III meningiomas. The proportion of patients with a deletion of 22q (either homogeneous or heterogeneous) who had recurrence was greater than the proportion of those without 22q deletion who had recurrence, and deletion of 22q was significantly associated with radiologically detected recurrence (P < 0

  12. Diagnostic and Prognostic Significance of Various Histopathological Features in Extrahepatic Biliary Atresia

    PubMed Central

    Karnan, Indumathi; Srinivasan, Padmanaban; Sadagopan, Pappathi; Manickam, Saraswathy

    2016-01-01

    Introduction Extrahepatic biliary atresia is a progressive disorder characterised by fibroinflammatory obliteration or stenosis of the extrahepatic biliary tree leading to obstruction of bile flow and cholestatic jaundice. It is the most common cause for cholestasis in newborn. Histopathological criteria for diagnosing biliary atresia from liver biopsy have not been clearly defined. Aim This study was undertaken to analyse the significance of the various histopathological features in diagnosis and prognosis of extrahepatic biliary atresia from liver biopsy specimens. Materials and Methods This was a retrospective study of 43 cases of extra-hepatic biliary atresia diagnosed and treated at a tertiary care hospital between January 2010 to December 2014. Formalin fixed paraffin embedded liver biopsy tissues were processed by standard technique and the slides were stained with haematoxylin and eosin. All the slides were reviewed and graded by a semi-quantitative scoring system. Features such as increased age at kasai’s portoenterostomy, portal fibrosis, bile duct proliferation, cholestasis, portal inflammation and duct plate malformation were studied. Statistical analysis was worked out using SPSS 17.0 (statistical package for the social science software). Chi-square test was used to find association between various parameters with respect to mortality and Kaplan-Meier estimator was used for survival analysis of the population under study. Results In this study comprising of 43 cases, only 6 cases (13.95%) were alive at the end of 6 months follow-up. Twenty patients who died and the 17 cases with poor survival had greater degrees of fibrosis, bile duct proliferation and cholestasis. Majority of the cases with duct plate malformation expired inspite of earlier surgical intervention. Thus proving the association of fibrosis, bile duct proliferation, cholestasis and duct plate malformation with the survival and prognosis of biliary atresia cases. Age at surgery did not

  13. The Prognostic Significance of Metabolic Response Heterogeneity in Metastatic Colorectal Cancer

    PubMed Central

    Hendlisz, Alain; Deleporte, Amelie; Delaunoit, Thierry; Maréchal, Raphaël; Peeters, Marc; Holbrechts, Stéphane; Van den Eynde, Marc; Houbiers, Ghislain; Filleul, Bertrand; Van Laethem, Jean-Luc; Ceyssens, Sarah; Barbuto, Anna-Maria; Lhommel, Renaud; Demolin, Gauthier; Garcia, Camilo; El Mansy, Hazem; Ameye, Lieveke; Moreau, Michel; Guiot, Thomas; Paesmans, Marianne; Piccart, Martine; Flamen, Patrick

    2015-01-01

    Background Tumoral heterogeneity is a major determinant of resistance in solid tumors. FDG-PET/CT can identify early during chemotherapy non-responsive lesions within the whole body tumor load. This prospective multicentric proof-of-concept study explores intra-individual metabolic response (mR) heterogeneity as a treatment efficacy biomarker in chemorefractory metastatic colorectal cancer (mCRC). Methods Standardized FDG-PET/CT was performed at baseline and after the first cycle of combined sorafenib (600mg/day for 21 days, then 800mg/day) and capecitabine (1700 mg/m²/day administered D1-14 every 21 days). MR assessment was categorized according to the proportion of metabolically non-responding (non-mR) lesions (stable FDG uptake with SUVmax decrease <15%) among all measurable lesions. Results Ninety-two patients were included. The median overall survival (OS) and progression-free survival (PFS) were 8.2 months (95% CI: 6.8–10.5) and 4.2 months (95% CI: 3.4–4.8) respectively. In the 79 assessable patients, early PET-CT showed no metabolically refractory lesion in 47%, a heterogeneous mR with at least one non-mR lesion in 32%, and a consistent non-mR or early disease progression in 21%. On exploratory analysis, patients without any non-mR lesion showed a significantly longer PFS (HR 0.34; 95% CI: 0.21–0.56, P-value <0.001) and OS (HR 0.58; 95% CI: 0.36–0.92, P-value 0.02) compared to the other patients. The proportion of non-mR lesions within the tumor load did not impact PFS/OS. Conclusion The presence of at least one metabolically refractory lesion is associated with a poorer outcome in advanced mCRC patients treated with combined sorafenib-capecitabine. Early detection of treatment-induced mR heterogeneity may represent an important predictive efficacy biomarker in mCRC. Trial Registration ClinicalTrials.gov NCT01290926 PMID:26421426

  14. Prognostic Significance of CREB-Binding Protein and CD81 Expression in Primary High Grade Non-Muscle Invasive Bladder Cancer: Identification of Novel Biomarkers for Bladder Cancer Using Antibody Microarray.

    PubMed

    Lee, Myung-Shin; Kim, Joo Heon; Lee, Ji-Su; Yun, Seok Joong; Kim, Wun-Jae; Ahn, Hanjong; Park, Jinsung

    2015-01-01

    High-grade (HG) bladder cancers (BCs) are genetically unstable and have an unpredictable course. The identification of prognostic factors in HG non-muscle invasive BC (NMIBC) is crucial for improving patients' quality of life and preventing BC-specific mortality. Here, we used an antibody microarray (AbM) to identify novel candidate biomarkers in primary HG NMIBC and validated the prognostic significance of the candidate biomarkers. Three pairs of tissue samples from primary HG NMIBC and normal urothelium were analyzed using an AbM kit containing 656 antibodies, and differentially expressed proteins were identified. Among the 42 upregulated and 14 downregulated proteins with statistical significance in BC tissues, CREB-binding protein and CD81 were selected as representative upregulated and downregulated candidate biomarkers, respectively. We then validated the expression of these candidate biomarkers in primary human urothelial cells and BC cell lines by western blotting and immunofluorescence assays, and the results were consistent with the AbM expression profiles. Additionally, Kaplan-Meier survival using immunohistochemical data from an independent primary HG NMIBC cohort comprising 113 patients showed that expression of the 2 biomarkers was significantly associated with recurrence-free and progression-free survival. In multivariate analysis, the 2 biomarkers remained significant predictors for recurrence-free survival. Taken together, our findings suggest that expression of CREB-binding protein and CD81 in BC tissue specimens may have prognostic value in patients with primary HG NMIBC. PMID:25915404

  15. Prognostic significance of bone marrow infiltration detected by PET-CT in newly diagnosed diffuse large B cell lymphoma

    PubMed Central

    Liang, Jin-Hua; Sun, Jin; Wang, Li; Fan, Lei; Chen, Yao-Yu; Qu, Xiao-Yan; Li, Tian-Nv; Li, Jian-Yong; Xu, Wei

    2016-01-01

    The aim of this study was to examine the prognostic value of bone marrow involvement (BMI) assessed by baseline PET-CT (PET(0)-BMI) in treatment-naïve patients with diffuse large B-cell lymphoma (DLBCL). All patients from a single centre diagnosed as DLBCL between 2005 and 2014 had data extracted from staging PET-CT (PET(0)-CT), bone marrow biopsy (BMB), and treatment records. The PET(3)-CT (PET-CT scan after cycle 3 of immunochemotherapy) was performed on all the patients with PET(0)-BMI positivity (PET(0)-BMI(+)). Of 169 patients, 20 (11.8%) had BMI on BMB, whereas 35 (20.7%) were PET(0)-BMI positive. Among PET(0)-BMI(+) patients, patients with maximum of standard uptake value (SUVmax) of bone marrow (SUVmax(BM)) more than 8.6 were significantly associated with high IPI score (3–5) (P=0.002), worse progression-free survival (PFS) and overall survival (OS) (P=0.025 and P=0.002, respectively). In the 68 stage IV cases, 3-year OS was higher in the patients with negative PET(0)-BMI (PET(0)-BMI(−)) than that with PET(0)-BMI(+) (84.2%±6.5% vs. 44.1%±8.6%; P=0.003), while 3-year PFS only shown a trend of statistic significance (P=0.077) between the two groups. Among the 69 patients of inter-risk of IPI (2–3), patients with PET(0)-BMI(+) had significantly inferior PFS and OS than that with PET(0)-BMI(−) (P=0.009 and P<0.001, respectively). The cut-off value of the decreased percentage of SUVmax(BM) between PET(0)-CT and PET(3)-CT (ΔSUVmax(BM)) was 70.0%, which can predict PFS (P=0.003) and OS (P=0.023). These data confirmed that along with the increased sensitivity and accuracy of identifying bone marrow by PET-CT, novel prognostic values of marrow involvement were found in patients with DLBCL. PMID:26919239

  16. Cytoplasmic accumulation of NCoR in malignant melanoma: consequences of altered gene repression and prognostic significance

    PubMed Central

    Padrón, Andreina; Garcia-Carbonell, Ricard; Rius, Cristina; González-Perez, Abel; Arumí-Uria, Montserrat; Iglesias, Mar; Nonell, Lara; Bellosillo, Beatriz; Segura, Sonia; Pujol, Ramon Maria; Lopez-Bigas, Nuria; Bertran, Joan

    2015-01-01

    Invasive malignant melanoma (MM) is an aggressive tumor with no curative therapy available in advanced stages. Nuclear corepressor (NCoR) is an essential regulator of gene transcription, and its function has been found deregulated in different types of cancer. In colorectal cancer cells, loss of nuclear NCoR is induced by Inhibitor of kappa B kinase (IKK) through the phosphorylation of specific serine residues. We here investigate whether NCoR function impacts in MM, which might have important diagnostic and prognostic significance. By IHC, we here determined the subcellular distribution of NCoR in a cohort of 63 primary invasive MM samples, and analyzed its possible correlation with specific clinical parameters. We therefore used a microarray-based strategy to determine global gene expression differences in samples with similar tumor stage, which differ in the presence of cytoplasmic or nuclear NCoR. We found that loss of nuclear NCoR results in upregulation of a specific cancer-related genetic signature, and is significantly associated with MM progression. Inhibition of IKK activity in melanoma cells reverts NCoR nuclear distribution and specific NCoR-regulated gene transcription. Analysis of public database demonstrated that inactivating NCoR mutations are highly prevalent in MM, showing features of driver oncogene. PMID:25823659

  17. Prognostic significance of B-cell lymphoma 2 expression in acute leukemia: A systematic review and meta-analysis

    PubMed Central

    LIU, YANFENG; HE, PENGCHENG; LIU, FENG; SHI, LILI; ZHU, HUACHAO; CHENG, XIAOYAN; ZHAO, JING; WANG, YUAN; ZHANG, MEI

    2014-01-01

    A number of studies have provided estimates of the correlation between B-cell lymphoma 2 (Bcl-2) expression and its clinical significance in acute leukemia (AL); however, the results have been heterogeneous. In order to clarify the prognostic significance of Bcl-2 status in patients with AL, a systematic review and meta-analysis of 5 published studies including a total of 665 subjects was performed. The reported frequency of Bcl-2 expression was 0–99.00%. Bcl-2-positive patients had a higher median white blood cell count compared to Bcl-2-negative patients. Additionally, Bcl-2-negative patients had >2-fold higher odds of achieving complete remission (CR) compared to Bcl-2-positive patients. The summary hazard ratio of Bcl-2 negativity/positivity for CR was 0.62 [95% confidence interval: 0.53–0.81, P<0.001]. Although this meta-analysis was based on data abstracted from observational studies, our results may justify the use of risk-adapted therapeutic strategies for AL according to the Bcl-2 expression status. PMID:24772309

  18. Elevation of circulating big endothelin-1: an independent prognostic factor for tumor recurrence and survival in patients with esophageal squamous cell carcinoma

    PubMed Central

    Jiao, Wenjie; Xu, Jing; Zheng, Jinsheng; Shen, Yi; Lin, Lesheng; Li, Jian

    2008-01-01

    Background Endothelin(ET) axis plays a key role in many tumor progression and metastasis via various mechanisms such as angiogenesis, mediating extracellular matrix degradation and inhibition of apoptosis. However, there is limited information regarding the clinical significance of plasma big ET-1 levels in esophageal cancer patients. Circulating plasma big ET-1 levels were measured in patients with esophageal squamous cell carcinoma(ESCC) to evaluate the value of ET-1 as a biomarker for predicting tumor recurrence and patients survival. Methods Preoperative plasma big ET-1 concentrations were measured by an enzyme linked immunosorbent assay(ELISA) in 108 ESCC patients before surgery, and then again at 1,2,3,10 and 30 days after curative radical resection for ESCC. The association between preoperative plasma big ET-1 levels and clinicopathological features, tumor recurrence and patient survival, and their changes following surgery were evaluated. Results The preoperative plasma big ET-1 levels in ESCC patients were significantly higher than those in controls. And there was a significant association between plasma big ET-1 levels and disease stage, as well as invasion depth of the tumor and lymph node status. Furthermore, plasma big ET-1 levels decreased significantly after radical resection of the primary tumor and patients with postoperative recurrence had significantly higher plasma big ET-1 levels than that of patients without recurrence. Finally, the survival rate of patients with higher plasma big ET-1 concentrations (>4.3 pg/ml) was significantly lower than that of patients with lower level (≤ 4.3 pg/ml). Multivariate regression analysis showed that plasma big ET-1 level is an independent prognostic factor for survival in patients with ESCC. Conclusion Plasma big ET-1 level in ESCC patients may reflect malignancy and predict tumor recurrence and patient survival. Therefore, the preoperative plasma big ET-1 levels may be a clinically useful biomarker for

  19. Prognostic Significance of the Systemic Inflammatory and Immune Balance in Alcoholic Liver Disease with a Focus on Gender-Related Differences

    PubMed Central

    Kasztelan-Szczerbińska, Beata; Surdacka, Agata; Celiński, Krzysztof; Roliński, Jacek; Zwolak, Agnieszka; Miącz, Sławomir; Szczerbiński, Mariusz

    2015-01-01

    Objectives Mechanisms of immune regulation in alcoholic liver disease (ALD) are still unclear. The aim of our study was to determine an impact of Th17 / regulatory T (Treg) cells balance and its corresponding cytokine profile on the ALD outcome. Possible gender-related differences in the alcohol-induced inflammatory response were also assessed. Materials and Methods 147 patients with ALD were prospectively recruited, assigned to subgroups based on their gender, severity of liver dysfunction and presence of ALD complications at admission, and followed for 90 days. Peripheral blood frequencies of Th17 and Treg cells together with IL-1beta, IL-6, IL-17A, IL-23, and TGF-beta1 levels were investigated. Flow cytometry was used to identify T cell phenotype and immunoenzymatic ELISAs for the corresponding cytokine concentrations assessment. Multivariable logistic regression was applied in order to select independent predictors of advanced liver dysfunction and the disease complications. Results IL-17A, IL-1beta, IL-6 levels were significantly increased, while TGF-beta1 decreased in ALD patients. The imbalance with significantly higher Th17 and lower Treg frequencies was observed in non-survivors. IL-6 and TGF-beta1 levels differed in relation to patient gender in ALD group. Concentrations of IL-6 were associated with the severity of liver dysfunction, development of ALD complications, and turned out to be the only independent immune predictor of 90-day survival in the study cohort. Conclusions We conclude that IL-6 revealed the highest diagnostic and prognostic potential among studied biomarkers and was related to the fatal ALD course. Gender-related differences in immune regulation might influence the susceptibility to alcohol-associated liver injury. PMID:26107937

  20. Ectopic expression of B and T lymphocyte attenuator in gastric cancer: a potential independent prognostic factor in patients with gastric cancer.

    PubMed

    Feng, Xing-Yu; Wen, Xi-Zhi; Tan, Xiao-Jing; Hou, Jing-Hui; Ding, Ya; Wang, Ke-Feng; Dong, Jun; Zhou, Zhi-Wei; Chen, Ying-Bo; Zhang, Xiao-Shi

    2015-01-01

    It has been confirmed that B and T lymphocyte attenuator (BTLA; also known as CD272) is a novel co--inhibitory molecule that exhibits a critical role in restraining cell-mediated antitumor immunity. The present study aimed to investigate the expression and prognostic significance of BTLA in gastric adenocarcinoma. Immunohistochemical (IHC) staining was performed to investigate BTLA expression in gastric cancer tissues and normal mucosal tissues. In total, 123 pathologically confirmed specimens were obtained from stage IIIa gastric cancers. A correlation test, Kaplan-Meier curves, and a Cox proportional hazards regression model were used to analyze the data. No BTLA staining in the normal tissues was found, while BTLA-stained gastric carcinoma cells were detected in 75.6% (93/123) of the gastric cancer specimens. High expression levels of BTLA were detected in 31.7% (39/123) of the specimens, while low expression levels were detected in 68.3% (84/123) of the specimens. High BTLA expression levels were associated with shorter survival time, as confirmed by univariate and multivariate analyses. These findings provide a basis for the concept that high BTLA expression levels in gastric cancer, identified by IHC, are an independent biomarker for the poor prognosis of patients with gastric cancer. PMID:25334051

  1. Prognostic significance of L1CAM expression and its association with mutant p53 expression in high-risk endometrial cancer.

    PubMed

    Van Gool, Inge C; Stelloo, Ellen; Nout, Remi A; Nijman, Hans W; Edmondson, Richard J; Church, David N; MacKay, Helen J; Leary, Alexandra; Powell, Melanie E; Mileshkin, Linda; Creutzberg, Carien L; Smit, Vincent T H B M; Bosse, Tjalling

    2016-02-01

    Studies in early-stage, predominantly low- and intermediate-risk endometrial cancer have demonstrated that L1 cell adhesion molecule (L1CAM) overexpression identifies patients at increased risk of recurrence, yet its prognostic significance in high-risk endometrial cancer is unclear. To evaluate this, its frequency, and the relationship of L1CAM with the established endometrial cancer biomarker p53, we analyzed the expression of both markers by immunohistochemistry in a pilot series of 116 endometrial cancers (86 endometrioid, 30 non-endometrioid subtype) with high-risk features (such as high tumor grade and deep myometrial invasion) and correlated results with clinical outcome. We used The Cancer Genome Atlas (TCGA) endometrial cancer series to validate our findings. Using the previously reported cutoff of 10% positive staining, 51/116 (44%) tumors were classified as L1CAM-positive, with no significant association between L1CAM positivity and the rate of distant metastasis (P=0.195). However, increasing the threshold for L1CAM positivity to 50% resulted in a reduction of the frequency of L1CAM-positive tumors to 24% (28/116), and a significant association with the rate of distant metastasis (P=0.018). L1CAM expression was strongly associated with mutant p53 in the high-risk and TCGA series (P<0.001), although a substantial fraction (36% of endometrioid, 10% of non-endometrioid morphology) of p53-mutant endometrial cancers displayed <10% L1CAM positivity. Moreover, 30% of p53-wild-type non-endometrioid endometrial cancers demonstrated diffuse L1CAM staining, suggesting p53-independent mechanisms of L1CAM overexpression. In conclusion, the previously proposed threshold for L1CAM positivity of >10% does not predict prognosis in high-risk endometrial cancer, whereas an alternative threshold (>50%) does. L1CAM expression is strongly, but not universally, associated with mutant p53, and may be strong enough for clinical implementation as prognostic marker in combination

  2. Clinical prognostic significance and pro-metastatic activity of RANK/RANKL via the AKT pathway in endometrial cancer.

    PubMed

    Wang, Jing; Liu, Yao; Wang, Lihua; Sun, Xiao; Wang, Yudong

    2016-02-01

    RANK/RANKL plays a key role in metastasis of certain malignant tumors, which makes it a promising target for developing novel therapeutic strategies for cancer. However, the prognostic value and pro-metastatic activity of RANK in endometrial cancer (EC) remain to be determined. Thus, the present study investigated the effect of RANK on the prognosis of EC patients, as well as the pro-metastatic activity of EC cells. The results indicated that those with high expression of RANK showed decreased overall survival and progression-free survival. Statistical analysis revealed the positive correlations between RANK/RANKL expression and metastasis-related factors. Additionally, RANK/RANKL significantly promoted cell migration/invasion via activating AKT/β-catenin/Snail pathway in vitro. However, RANK/RANKL-induced AKT activation could be suppressed after osteoprotegerin (OPG) treatment. Furthermore, the combination of medroxyprogesterone acetate (MPA) and RANKL could in turn attenuate the effect of RANKL alone. Similarly, MPA could partially inhibit the RANK-induced metastasis in an orthotopic mouse model via suppressing AKT/β-catenin/Snail pathway. Therefore, therapeutic inhibition of MPA in RANK/RANKL-induced metastasis was mediated by AKT/β-catenin/Snail pathway both in vitro and in vivo, suggesting a potential target of RANK for gene-based therapy for EC. PMID:26734994

  3. An examination of the hypothesis that intraocular pressure elevation episodes can have prognostic significance in glaucoma suspects

    PubMed Central

    McMonnies, Charles

    2014-01-01

    The efficacy of intraocular pressure reduction in retarding the progression of glaucoma has been demonstrated. This review examines the potential for prognostic advantage for glaucoma suspects in reducing their optic nerve head exposure to elevated intraocular pressure associated with activities which have been shown to elevate intraocular pressure. In this observational study, patients examined at the Centre for Eye Health (University of New South Wales) with a diagnosis of glaucoma suspect were surveyed to determine their histories for participation in activities which are known to elevate intraocular pressure. The evidence regarding the pathological significance of these sources of elevation in susceptible patients was examined. Apart from the universality of sleep-related intraocular pressure elevations, the histories from 183 confirmed glaucoma suspects indicate a wide range and variation in frequency of participation in other intraocular pressure elevating activities. A reduction in exposure to elevated intraocular pressure may improve the prognosis for glaucoma suspects. Additional patient specific assessment of the results of this screening could provide an indication of the degree (frequency, intensity level and duration) of exposure to elevated intraocular pressure. Such information may provide the basis for improving a patient's prognosis by helping them to identify opportunities to reduce such exposure to elevated intraocular pressure. Any benefit of reduction of such exposure appears likely to be greater if activities which elevate intraocular pressure are of long duration, occur frequently, occur over a long period of time, and/or involve high levels of intraocular pressure elevation. PMID:25199440

  4. Clinical prognostic significance and pro-metastatic activity of RANK/RANKL via the AKT pathway in endometrial cancer

    PubMed Central

    Wang, Jing; Liu, Yao; Wang, Lihua; Sun, Xiao; Wang, Yudong

    2016-01-01

    RANK/RANKL plays a key role in metastasis of certain malignant tumors, which makes it a promising target for developing novel therapeutic strategies for cancer. However, the prognostic value and pro-metastatic activity of RANK in endometrial cancer (EC) remain to be determined. Thus, the present study investigated the effect of RANK on the prognosis of EC patients, as well as the pro-metastatic activity of EC cells. The results indicated that those with high expression of RANK showed decreased overall survival and progression-free survival. Statistical analysis revealed the positive correlations between RANK/RANKL expression and metastasis-related factors. Additionally, RANK/RANKL significantly promoted cell migration/invasion via activating AKT/β-catenin/Snail pathway in vitro. However, RANK/RANKL-induced AKT activation could be suppressed after osteoprotegerin (OPG) treatment. Furthermore, the combination of medroxyprogesterone acetate (MPA) and RANKL could in turn attenuate the effect of RANKL alone. Similarly, MPA could partially inhibit the RANK-induced metastasis in an orthotopic mouse model via suppressing AKT/β-catenin/Snail pathway. Therefore, therapeutic inhibition of MPA in RANK/RANKL-induced metastasis was mediated by AKT/β-catenin/Snail pathway both in vitro and in vivo, suggesting a potential target of RANK for gene-based therapy for EC. PMID:26734994

  5. Prognostic significance of drainage to pelvic nodes at sentinel lymph node mapping in patients with extremity melanoma.

    PubMed

    Karakousis, Giorgos C; Pandit-Taskar, Neeta; Hsu, Meier; Panageas, Katherine; Atherton, Sonny; Ariyan, Charlotte; Brady, Mary S

    2013-02-01

    Patients undergoing sentinel lymph node (SLN) mapping for lower extremity melanoma may have drainage to pelvic nodes (DPN) in addition to superficial inguinal nodes. These nodes are not sampled routinely at SLN biopsy. Factors predicting DPN and its prognostic significance were assessed in a large cohort of patients undergoing an SLN biopsy. Three hundred and twenty five patients with single primary melanomas of the lower extremity or buttocks who underwent SLN mapping were identified from our prospective melanoma database (December 1995-October 2008). Associations of clinical and pathologic factors with DPN and time to melanoma recurrence (TTR) were analyzed by logistic and Cox regression, respectively. DPN was common, occurring in 23% of cases. Increased Breslow's thickness (P=0.007) and age (P=0.01) were associated with DPN by multivariate analysis. Patients with DPN were not more likely to have a positive SLN; however, SLN- patients with DPN showed a shorter TTR (P=0.02) in a multivariable model including thickness and ulceration. With age included in the model, DPN remained marginally associated with TTR in this group (P=0.08). The pelvic recurrence rates observed were similar in recurrent patients with DPN compared with those without DPN (39% in both groups). In conclusion, DPN occurs in almost one-quarter of patients with lower extremity melanoma and is marginally associated with a shorter TTR in SLN- patients. PMID:23250048

  6. An examination of the hypothesis that intraocular pressure elevation episodes can have prognostic significance in glaucoma suspects.

    PubMed

    McMonnies, Charles

    2015-01-01

    The efficacy of intraocular pressure reduction in retarding the progression of glaucoma has been demonstrated. This review examines the potential for prognostic advantage for glaucoma suspects in reducing their optic nerve head exposure to elevated intraocular pressure associated with activities which have been shown to elevate intraocular pressure. In this observational study, patients examined at the Centre for Eye Health (University of New South Wales) with a diagnosis of glaucoma suspect were surveyed to determine their histories for participation in activities which are known to elevate intraocular pressure. The evidence regarding the pathological significance of these sources of elevation in susceptible patients was examined. Apart from the universality of sleep-related intraocular pressure elevations, the histories from 183 confirmed glaucoma suspects indicate a wide range and variation in frequency of participation in other intraocular pressure elevating activities. A reduction in exposure to elevated intraocular pressure may improve the prognosis for glaucoma suspects. Additional patient specific assessment of the results of this screening could provide an indication of the degree (frequency, intensity level and duration) of exposure to elevated intraocular pressure. Such information may provide the basis for improving a patient's prognosis by helping them to identify opportunities to reduce such exposure to elevated intraocular pressure. Any benefit of reduction of such exposure appears likely to be greater if activities which elevate intraocular pressure are of long duration, occur frequently, occur over a long period of time, and/or involve high levels of intraocular pressure elevation. PMID:25199440

  7. Symptomatic Chiari malformation in adults: a new classification based on magnetic resonance imaging with clinical and prognostic significance.

    PubMed

    Pillay, P K; Awad, I A; Little, J R; Hahn, J F

    1991-05-01

    Thirty-five consecutive adults with Chiari malformation and progressive symptoms underwent surgical treatment at a single institution over a 3-year period. All patients underwent magnetic resonance imaging scan before and after surgery. Images of the craniovertebral junction confirmed tonsillar herniation in all cases and allowed the definition of two anatomically distinct categories of the Chiari malformation in this age group. Twenty of the 35 patients had concomitant syringomyelia and were classified as Type A. The remaining 15 patients had evidence of frank herniation of the brain stem below the foramen magnum without evidence of syringomyelia and were labeled Type B. Type A patients had a predominant central cord symptomatology; Type B patients exhibited signs and symptoms of brain stem or cerebellar compression. The principal surgical procedure consisted of decompression of the foramen magnum, opening of the fourth ventricular outlet, and plugging of the obex. Significant improvement in preoperative symptoms and signs was observed in 9 of the 20 patients (45%) with syringomyelia (Type A), as compared to 13 of the 15 patients (87%) without syringomyelia (Type B). Postoperative reduction in syrinx volume was observed in 11 of the 20 patients with syringomyelia, including all 9 patients with excellent results. Magnetic resonance imaging has allowed a classification of the adult Chiari malformation in adults based on objective anatomic criteria, with clinical and prognostic relevance. The presence of syringomyelia implies a less favorable response to surgical intervention. PMID:1876240

  8. Prognostic significance of foveal capillary drop-out and previous panretinal photocoagulation for diabetic macular oedema treated with ranibizumab

    PubMed Central

    Ebneter, Andreas; Wolf, Sebastian; Zinkernagel, Martin S

    2016-01-01

    Aims To investigate the prognostic significance of macular capillary drop-out and previous panretinal laser photocoagulation in diabetic macular oedema treated with intravitreal ranibizumab. Methods Retrospective observational case series. Treatment-naive patients with diabetic macular oedema that had been treated with intravitreal ranibizumab as per the RESTORE study protocol for at least 12 months were included. Some patients (n=15) had previous panretinal laser photocoagulation. Best-corrected visual acuity and central retina thickness were recorded monthly. The foveal avascular zone and the perifoveal capillaries were quantitatively and qualitatively assessed on fluorescein angiography on two occasions during the observational period. Results From the 46 eyes (46 patients) in this study, 13 (28%) had evidence of perifoveal capillary drop-out. Central retinal thickness was significantly thinner at baseline (p=0.02) and throughout the study period in these eyes compared with those with normal perifoveal capillaries. Both groups responded with a significant gain of best-corrected visual acuity to ranibizumab treatment (7.6±3.3 and 6.3±1.3 ETDRS letters, respectively). Eyes with previous panretinal laser photocoagulation displayed a comparable final outcome regarding function and morphology, requiring a similar intensity of intravitreal injections. Conclusions Perifoveal capillary drop-out did not limit the gain of visual acuity from intravitreal ranibizumab treatment. The reduction of central retina thickness was similar to that seen in eyes with normal perifoveal capillaries. Central retinal thickness in eyes with perifoveal capillary drop-out was generally reduced. However, this did not affect their benefit from treatment. Ranibizumab did not increase the amount of perifoveal capillary loss. PMID:26187951

  9. Prognostic significance of full-length estrogen receptor beta expression in stage I-III triple negative breast cancer

    PubMed Central

    Shanle, Erin K; Onitilo, Adedayo A; Huang, Wei; Kim, KyungMann; Zang, Chong; Engel, Jessica M; Xu, Wei; Wisinski, Kari B

    2015-01-01

    Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which there is a need to identify new therapeutic targets. Full-length estrogen receptor beta (ERβ1) may be a possible target given its antiproliferative effects on breast cancer cells. The prognostic significance of ERβ in breast cancer subtypes has remained elusive, and disparate results observed across previously published reports might be due to the detection of multiple ERβ isoforms, the lack of specific antibodies and the use of different cutoffs to define ERβpositivity. The objective of this retrospective study was to determine the association between ERβ1 expression and disease-free and overall survival, as well as Ki67 expression, in non-metastatic TNBC. Immunohistochemical protocols were optimized using xenograft tissues obtained from a breast cancer cell line with inducible ERβ1 expression. ERβ1 localization and expression were assessed in two cohorts of TNBC using the VECTRATM platform. There was a close relationship between nuclear and cytoplasmic ERβ1 expression. ERβ1 was expressed in a subset of TNBCs, but its expression was significantly associated with Ki67 in only one of the cohorts. There was no significant association between ERβ1 expression and disease-free and overall survival in either cohort. Although these results suggest that ERβ1 expression alone may not be informative in TNBCs, this study provides a new strategy for optimizing and objectively measuring ERβ1 expression in tissues, which may provide a standard for ERβ1 immunohistochemistry in future large-scale clinical studies aimed at better understanding the role of ERβ1 in breast cancer. PMID:26328009

  10. [u-Plasminogen activator (urinary plasminogen activator, urokinase) (uPA) and its PA-1 type 1 inhibitor are not only prognostically but also predictively significant and support clinical decisions on therapy in primary carcinoma of the breast].

    PubMed

    Harbeck, N; Thomssen, C

    2003-09-01

    uPA and PAI-1 are the first novel tumor biological prognostic factors in breast cancer for which the prognostic impact has been validated at the highest level of evidence and hence all evaluation criteria for transfer into clinical practice have been fullfilled. Breast cancer patients with high uPA and/or PAI-1 levels in their primary tumor tissue have a significantly lower chance for cure than patients with low levels of both uPA and PAI-1. Our research that was honored with the Schmidt-Matthiesen-Award 2002 shows for the first time that uPA and PAI-1 are not only prognostic factors but also have a predictive impact with regard to response to adjuvant chemotherapy. Patients with high uPA/PAI-1 derive a significantly greater benefit from adjuvant chemotherapy than patients with low uPA/PAI-1. Benefit from adjuvant endocrine therapy is independent of uPA/PAI-1 status. The resulting question about the optimal chemotherapy for patients with high uPA/PAI-1 is currently being addressed in Germany by the NNBC-3 trial in node-negative breast cancer (AGO, EORTC-RBG) as well as the ADEBAR trial in patients with 4 or more involved axillary lymph nodes. Moreover, our results suggest the use of novel therapeutic agents interfering with the uPA system together with conventional chemotherapy in patients with high uPA/PAI-1 already in early stage disease. PMID:14569518

  11. Outcomes in Young Women With Breast Cancer of Triple-Negative Phenotype: The Prognostic Significance of CK19 Expression

    SciTech Connect

    Parikh, Rahul R.; Yang Qifeng; Higgins, Susan A.; Haffty, Bruce G.

    2008-01-01

    Purpose: Basal-like carcinoma of the breast is associated with genetic instability and aggressive behavior. In this study, we evaluated the luminal cytokeratin marker CK-19 in young women with breast cancer treated with conservative surgery and radiation therapy (CS+RT). Methods: Primary tumor specimens from a cohort of 158 young premenopausal women (range, 25-49 years) treated with CS+RT with a median follow-up of 6.25 years were constructed into a tissue microarray. The array was stained for ER, PR, HER2, CK19, and p53. The molecular profiles were correlated with clinical-pathologic factors, overall, local, and distant relapse-free survival. The association between CK19, other co-variables, and outcome was assessed in a multivariate model. Results: Positive expression of ER, PR, HER-2/neu, CK19, and p53 were 33.1%, 34.5%, 10.0%, 79.5%, and 20.9%, respectively. With 20 local relapses and 38 distant metastases, the 10-year overall, breast relapse-free, and distant relapse-free survival were 79.65%, 87.29%, and 67.35%, respectively. Tumor stage and nodal status were associated with distant relapse-free and overall survival. In multivariate analysis, CK19 negativity was a predictor poor local (RR, 3.54; 95% CI, 1.87-7.65; p < 0.01) distant (RR, 1.44; 95% CI, 0.86-2.70; p = 0.17), and overall survival (RR, 1.89; 95% CI, 1.04-3.55; p = 0.03). Conclusions: Lack of CK19 expression identifies a subset of patients with a significantly higher risk of local relapse. Distant relapse and overall survival rates also correlated with CK19 negativity. Further evaluation of the prognostic significance of basal and luminal cytokeratins in young women with breast cancer is warranted.

  12. The prognostic significance of tumor epidermal growth factor receptor (EGFR) expression change after neoadjuvant chemoradiation in patients with rectal adenocarcinoma

    PubMed Central

    Dvořák, Josef; Urbanec, Marek; Bluml, Antonin; Čermáková, Eva; Bartoš, Jiří; Petera, Jiří

    2015-01-01

    Aim of the study The aim of this retrospective study was to determine the prognostic impact of epidermal growth factor receptor (EGFR) expression changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer. Material and methods Fifty patients with locally advanced rectal cancer were evaluated. All the patients were administered the total dose of 44 Gy. Capecitabine has been concomitantly administered in the dose 825 mg/m2 in two daily oral administrations. Surgery was indicated 4–8 weeks from the chemoradiotherapy completion. Epidermal growth factor receptor expression in the pretreatment biopsies and in the resected specimens was assessed with immunohistochemistry. Results All of 50 patients received radiotherapy without interruption up to the total planned dose. In 30 patients sphincter-saving surgery was performed, 20 patients underwent amputation of the rectum. Downstaging was described in 30 patients. Four patients have had complete pathologic remission. Twenty-six patients have had partial remission, the disease was stable in 15 patients. Progression was reported in 5 patients. The median disease-free survival was 64.9 months, median overall survival was 76.4 months. Increased EGFR expression was found in 12 patients (26.1%). A statistically significantly shorter overall survival (p < 0.0001) and disease-free survival (p < 0.0001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR during neoadjuvant chemoradiotherapy was observed. Conclusions The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenokarcinoma associated with significant shorter overall survival and disease free survival. PMID:26199571

  13. Prognostic significance of epithelial-mesenchymal transition proteins Twist and Foxc2 in phyllodes tumours of the breast.

    PubMed

    Lim, Jeffrey Chun Tatt; Koh, Valerie Cui Yun; Tan, Jane Sie Yong; Tan, Wai Jin; Thike, Aye Aye; Tan, Puay Hoon

    2015-02-01

    Epithelial-mesenchymal transition (EMT), an important process during embryonic development, is reportedly exploited during tumour progression. Deregulation of EMT-related molecules has been shown in many malignancies, including breast carcinoma. We aim to investigate the clinical relevance and prognostic significance of EMT proteins, Twist and Foxc2, in breast phyllodes tumours (PTs). The study cohort comprised 271 PTs diagnosed from 2003 to 2010. Of these, 188 (69.4 %) were benign, 60 (22.1 %) borderline, and 23 (8.5 %) malignant. Immunohistochemistry for Twist and Foxc2 was performed on tissue microarray sections. Percentage of tumour cells stained was evaluated and correlated with clinicopathological parameters and clinical outcome. Twist and Foxc2 stromal nuclear expression was associated with tumour grade (P = 0.038 and 0.012). Foxc2 stromal nuclear expression was positively correlated with epithelial expression (P < 0.001), tumour relapse, and metastasis (P = 0.037). Furthermore, stromal nuclear immunoreactivity of Twist and Foxc2 was interrelated (P < 0.001). Tumours expressing Foxc2 and those co-expressing both Twist and Foxc2 revealed a shorter time to recurrence (P < 0.001 and 0.001) and death (P = 0.044 and 0.015). Twist and Foxc2 stromal expression in PTs was significantly correlated with tumour grade and worse histological features. In addition, expression of Foxc2 and co-expression of Twist and Foxc2 in the stroma of PTs contributed to poorer prognosis. Clinical relevance of EMT-related molecules may be worthy of further investigation in PTs. PMID:25677742

  14. Prognostic significance of PRAME expression based on immunohistochemistry for diffuse large B-cell lymphoma patients treated with R-CHOP therapy.

    PubMed

    Mitsuhashi, Kenjiro; Masuda, Akihiro; Wang, Yan-Hua; Shiseki, Masayuki; Motoji, Toshiko

    2014-07-01

    The preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is considered a prognostic marker for various human malignancies. The prognostic significance of PRAME expression for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab-containing chemotherapy has not been evaluated to date, and the ability of immunohistochemistry (IHC) to detect PRAME expression in these patients has not yet been studied, although IHC is simple to perform in clinical practice. We evaluated the prognostic significance of PRAME expression based on IHC analysis in 160 DLBCL patients treated with R-CHOP therapy. There was a significant association between higher PRAME expression and shorter progression-free survival (PFS), and a trend toward shorter overall survival (OS) in patients with higher PRAME expression than that in patients with lower PRAME expression (5-year PFS, 48.1 vs. 61.1 %; 5-year OS, 65.6 vs. 79.1 %). Patients with high PRAME expression tended to have lower chemotherapeutic responses. Thus, IHC is useful for detecting and assessing PRAME expression in DLBCL. Further, we found a positive correlation between IHC and quantitative real-time RT-PCR measurements of PRAME expression. Our findings indicate that IHC results of PRAME expression can be a novel prognostic maker in DLBCL patients treated with R-CHOP therapy. PMID:24820636

  15. IGHV gene mutational status and 17p deletion are independent molecular predictors in a comprehensive clinical-biological prognostic model for overall survival prediction in chronic lymphocytic leukemia

    PubMed Central

    2012-01-01

    Background Prognostic index for survival estimation by clinical-demographic variables were previously proposed in chronic lymphocytic leukemia (CLL) patients. Our objective was to test in a large retrospective cohort of CLL patients the prognostic power of biological and clinical-demographic variable in a comprehensive multivariate model. A new prognostic index was proposed. Methods Overall survival and time to treatment in 620 untreated CLL patients were analyzed retrospectively to evaluate the multivariate independence and predictive power of mutational status of immunoglobulin heavy chain variable gene segments (IGHV), high-risk chromosomal aberration such as 17p or 11q deletions, CD38 and ZAP-70 expression, age, gender, Binet stage, β2-microglobulin levels, absolute lymphocyte count and number of lymph node regions. Results IGHV mutational status and 17p deletion were the sole biological variables with independent prognostic relevance in a multivariate model for overall survival, which included easily measurable clinical parameters (Binet staging, β2-microglobulin levels) and demographics (age and gender). Analysis of time to treatment in Binet A patients below 70 years of age showed that IGHV was the most important predictor. A novel 6-variable clinical-biological prognostic index was developed and internally validated, which assigned 3 points for Binet C stage, 2 points/each for Binet B stage and for age > 65 years, 1 point/each for male gender, high β2-microglobulin levels, presence of an unmutated IGHV gene status or 17p deletion. Patients were classified at low-risk (score = 0-1; 21%), intermediate-risk (score 2-5; 63% of cases), high-risk (score 6-9; 16% of cases). Projected 5-year overall survival was 98%, 90% and 58% in low-, intermediate- and high-risk groups, respectively. A nomogram for individual patient survival estimation was also proposed. Conclusions Data indicate that IGHV mutational status and 17p deletion may be integrated with clinical

  16. Prognostic Significance and Treatment Implications of Minimal Residual Disease Studies in Philadelphia-Negative Adult Acute Lymphoblastic Leukemia

    PubMed Central

    Spinelli, Orietta; Tosi, Manuela; Peruta, Barbara; Guinea Montalvo, Marie Lorena; Maino, Elena; Scattolin, Anna Maria; Parolini, Margherita; Viero, Piera; Rambaldi, Alessandro; Bassan, Renato

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is curable in about 40–50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates. PMID:25237475

  17. Persistence of Cytogenetic Abnormalities at Complete Remission After Induction in Patients With Acute Myeloid Leukemia: Prognostic Significance and the Potential Role of Allogeneic Stem-Cell Transplantation

    PubMed Central

    Chen, Yiming; Cortes, Jorge; Estrov, Zeev; Faderl, Stefan; Qiao, Wei; Abruzzo, Lynne; Garcia-Manero, Guillermo; Pierce, Sherry; Huang, Xuelin; Kebriaei, Partow; Kadia, Tapan; De Lima, Marcos; Kantarjian, Hagop; Ravandi, Farhad

    2011-01-01

    Purpose To determine the prognostic impact of persistent cytogenetic abnormalities at complete remission (CR) on relapse-free survival (RFS) and overall survival (OS) in patients with acute myeloid leukemia (AML) and to examine the potential role of allogeneic stem-cell transplantation (SCT) in this setting. Patients and Methods Data from 254 adult patients with AML (excluding acute promyelocytic leukemia) who achieved CR after induction chemotherapy on various first-line protocols were examined. Results Median follow-up for surviving patients was 43 months. Patients with cytogenetic abnormalities at CR (n = 71) had significantly shorter RFS (P = .001) and OS (P < .001) compared with patients with normal cytogenetics at CR (n = 183); 3-year RFS was 15% and 45%, and 3-year OS was 15% and 56%, respectively. Among the patients with persistent cytogenetic abnormalities at CR, those who underwent SCT in first CR (CR1; n = 15) had better RFS and OS compared to those without SCT (n = 56; P = .04 and .06, respectively). In multivariate analysis, persistent cytogenetic abnormalities at CR was an independent predictor for RFS (P < .001) and OS (P = .001), but among patients with persistent cytogenetic abnormalities at CR, no significant differences in OS (P = .25) was observed between those who did or did not receive SCT with a trend favoring SCT for RFS (P = .08). Conclusion Persistent cytogenetically abnormal cells at CR predict a significantly shorter RFS and OS. SCT in CR1 may improve the clinical outcome of patients lacking cytogenetic remission after induction although this depends on patient selection. PMID:21555694

  18. Prognostic Significance of KIT Mutations in Core-Binding Factor Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

    PubMed Central

    Wang, Hongxiang; Chen, Li; Sun, Yi; Chen, Zhichao; Li, Qiubai

    2016-01-01

    The prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia (CBF-AML), including inv(16) and t(8;21) AML, is uncertain. We performed a systematic review and meta-analysis of the effect of KIT mutations on the complete remission (CR) and relapse rates and overall survival (OS) of CBF-AML. PubMed, Embase, Web of Science, and the Cochrane Library were searched and relevant studies were included. Negative effect was indicated on relapse risk of CBF-AML (RR [relative risk], 1.43; 95%CI [confidence interval], 1.20–1.70) and t(8;21) AML (RR, 1.70; 95% CI, 1.31–2.21), not on OS of CBF-AML (RR, 1.09; 95% CI, 0.97–1.23), CR (OR [odds ratio], 0.95; 95% CI, 0.52–1.74), relapse risk (RR, 1.12; 95% CI, 0.90–1.41) or OS (RR, 1.03; 95% CI, 0.90–1.18) of inv(16) AML. Subgroup analysis of t(8,21) AML showed negative effect of KIT mutations on CR (OR, 2.03; 95%CI: 1.02–4.05), relapse risk (RR, 1.89; 95%CI: 1.51–2.37) and OS (RR, 2.26; 95%CI: 1.35–3,78) of non-Caucasians, not on CR (OR, 0.61; 95%CI: 0.19–1.95) or OS (RR, 1.12; 95%CI: 0.90–1.40) of Caucasians. This study indicates KIT mutations in CBF-AML to be included in the initial routine diagnostic workup and stratification system of t(8,21) AML. Prospective large-scale clinical trials are warranted to evaluate these findings. PMID:26771376

  19. Prognostic Significance of Transverse Relaxation Rate (R2*) in Blood Oxygenation Level-Dependent Magnetic Resonance Imaging in Patients with Invasive Breast Cancer

    PubMed Central

    Choi, Hye Young; Ko, Eun Sook; Han, Boo-Kyung; Kim, Eun Ju; Kim, Sun Mi; Lim, Yaeji; Kim, Rock Bum

    2016-01-01

    Objective To examine the relationship between magnetic resonance transverse relaxation rate (R2*) and prognostic factors. Materials and Methods A total of 159 women with invasive ductal carcinomas (IDCs) underwent breast magnetic resonance imaging (MRI) including blood oxygenation level-dependent (BOLD) sequence at 3 T. The distribution of the measured R2* values were analyzed, and the correlation between R2* and various prognostic factors (age, tumor size, histologic grade, lymphovascular invasion, and axillary lymph node status, as well as expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, p53, and Ki-67) were retrospectively assessed using patient medical records. Results The baseline R2* values of the IDCs were very heterogeneous with wide range among the patients. The mean R2* value was (32.8 ± 14.0) Hz with a median of 29.3 Hz (range 13.5–109.4 Hz). In multivariate analysis, older age was associated with decreased R2* value (P = 0.011) and IDCs with p53-overexpression showed higher R2* values than those without p53-overexpression group (P = 0.031). Other prognostic factors were not significantly correlated with R2* value. Conclusion In this study, R2* values were significantly correlated with age and expression of p53. Further studies are necessary to determine the prognostic value of BOLD-MRI. PMID:27384310

  20. Clinical Characteristics and Prognostic Significance of TERT Promoter Mutations in Cancer: A Cohort Study and a Meta-Analysis

    PubMed Central

    Yuan, Ping; Cao, Jin-lin; Abuduwufuer, Abudumailamu; Wang, Lu-Ming; Yuan, Xiao-Shuai; Lv, Wang; Hu, Jian

    2016-01-01

    Background The prevalence of telomerase reverse transcriptase (TERT) promoter mutations (pTERTm) in non-small-cell lung cancer (NSCLC) have been investigated, but the results were inconsistent. In addition, several studies have analysed the role of pTERTm in the etiology of various types of cancers, however, the results also remain inconsistent. Methods The genomic DNA sequence of 103 NSCLC samples were analysed to investigate the frequency of pTERTm in these patients and to establish whether these mutations are associated with their clinical data. Furthermore, a meta-analysis based on previously published articles and our cohort study was performed to investigate the association of pTERTm with patient gender, age at diagnosis, metastasis status, tumour stage and cancer prognosis (5-year overall survival rate). Results In the cohort study, 4 patients had C228T and 2 had C250T, with a total mutation frequency up to 5.8%. Significant difference of clinical data between pTERTm carriers and noncarriers was only found in age at diagnosis. In the meta-analysis, We found that pTERTm carriers in cancer patients are older than noncarriers (Mean difference (MD) = 5.24; 95% confidence interval [CI], 2.00 to 8.48), male patients were more likely to harbour pTERTm (odds Ratios (OR) = 1.38; 95% CI, 1.22 to 1.58), and that pTERTm had a significant association with distant metastasis (OR = 3.78; 95% CI, 2.45 to 5.82), a higher tumour grade in patients with glioma (WHO grade III, IV vs. I, II: OR, 2.41; 95% CI, 1.88 to 3.08) and a higher tumour stage in other types of cancer (III, IV vs. I, II: OR, 2.48; 95% CI, 1.48 to 4.15). pTERTm was also significantly associated with a greater risk of death (hazard ratio = 1.71; 95% CI, 1.41 to 2.08). Conclusions pTERTm are a moderately prevalent genetic event in NSCLC. The current meta-analysis indicates that pTERTm is associated with patient age, gender and distant metastasis. It may serves as an adverse prognostic factor in individuals with

  1. Prognostic Significance of CDKN2A (p16) Promoter Methylation and Loss of Expression in 902 Colorectal Cancers: Cohort Study and Literature Review

    PubMed Central

    Shima, Kaori; Nosho, Katsuhiko; Baba, Yoshifumi; Cantor, Mami; Meyerhardt, Jeffrey A.; Giovannucci, Edward L.; Fuchs, Charles S.; Ogino, Shuji

    2010-01-01

    A cyclin-dependent kinase inhibitor CDKN2A (p16/Ink4a) is a tumor suppressor and upregulated in cellular senescence. CDKN2A promoter methylation and gene silencing are associated with the CpG island methylator phenotype (CIMP) in colon cancer. However, prognostic significance of CDKN2A methylation or loss of CDKN2A (p16) expression independent of CIMP status remains uncertain. Utilizing a database of 902 colorectal cancers in two independent cohort studies (the Nurses' Health Study and the Health Professionals Follow-up Study), we quantified CDKN2A promoter methylation and detected hypermethylation in 269 tumors (30%). By immunohistochemistry, we detected loss of CDKN2A (p16) expression in 25% (200/804) of tumors. We analyzed for LINE-1 hypomethylation and hypermethylation at 7 CIMP-specific CpG islands (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); microsatellite instability (MSI); KRAS, BRAF and PIK3CA mutations; and expression of TP53 (p53), CTNNB1 (β-catenin), CDKN1A (p21), CDKN1B (p27), CCND1 (cyclin D1), FASN (fatty acid synthase), and PTGS2 (cyclooxygenase-2). CDKN2A promoter methylation and loss of CDKN2A (p16) were associated with shorter overall survival in univariate Cox regression analysis [hazard ratio (HR), 1.36; 95% CI, 1.10-1.66; p=0.0036 for CDKN2A methylation; HR, 1.30; 95% CI, 1.03-1.63; p=0.026 for CDKN2A (p16) loss] but not in multivariate analysis that adjusted for clinical and tumor variables including CIMP, MSI, and LINE-1 methylation. Neither CDKN2A promoter methylation nor loss of CDKN2A (p16) was associated with colorectal cancer-specific mortality in univariate or multivariate analysis. Despite its well-established role in carcinogenesis, CDKN2A (p16) promoter methylation or loss of expression in colorectal cancer is not independently associated with patient prognosis. PMID:20473920

  2. Presence of tumour high-endothelial venules is an independent positive prognostic factor and stratifies patients with advanced-stage oral squamous cell carcinoma.

    PubMed

    Wirsing, Anna M; Rikardsen, Oddveig G; Steigen, Sonja E; Uhlin-Hansen, Lars; Hadler-Olsen, Elin

    2016-02-01

    Staging of oral squamous cell carcinoma is based on the tumour-node-metastasis (TNM) system, which has been deemed insufficient for prognostic purposes. Hence, better prognostic tools are needed to reflect the biological diversity of these cancers. Previously, high numbers of specialized blood vessels called high-endothelial venules have been reported to be associated with prolonged survival in patients with breast cancer. In this study, we analysed the prognostic value and morphological characteristics of tumour-associated high-endothelial venules in oral cancer. The presence of tumour-associated high-endothelial venules was evaluated by immunohistochemistry in 75 patients with oral squamous cell carcinoma and analysed with correlation to clinicopathological parameters, patients' survival and vessel morphology. Ten of the samples were analysed at multiple levels to evaluate intratumoural heterogeneity. The presence of tumour-associated high-endothelial venules was found to be associated with lower disease-specific death in multivariate regression analyses (P = 0.002). High-endothelial venules were present in all (n = 53) T1-T2 tumours, but only in two thirds (n = 14) of the T3-T4 tumours. The morphology of high-endothelial venules was heterogeneous and correlated with lymphocyte density. High-endothelial venules were found to be distributed homogeneously within the tumours. We found the presence of tumour-associated high-endothelial venules to be an easy-to-use, robust, and independent positive prognostic factor for patients with oral cancer. Absence of these vessels in advanced-stage tumours might identify patients with more aggressive disease. Evaluating the presence of tumour-associated high-endothelial venules might help to tailor the treatment of oral cancer patients to their individual needs. PMID:26383526

  3. Prognostic significance of c-KIT in vulvar cancer: bringing this molecular marker from bench to bedside

    PubMed Central

    2012-01-01

    Background Vulvar carcinomas are rare tumors, and there is limited data regarding molecular alterations. To our knowledge there are no published studies on c-KIT and squamous cell carcinomas of the vulva (VSCC). Although there are a significant number of other tumor types which express c-KIT, there remains controversy as to its relationship to patient outcome. Thus, we wished to investigate such controversial findings to determine the prognostic importance of c-KIT by evaluating its protein and mRNA expression in VSCCs, correlating these findings with clinicopathological features and Human Papillomavirus (HPV) infection. Methods c-KIT expression was scored by immunohistochemistry (IHC) as positive or negative in 139 formalin-fixed paraffin-embedded (FFPE) cases of vulvar carcinomas arrayed in a tissue microarray (TMA) using the DAKO® A4502 rabbit polyclonal c-KIT antibody (diluted 1:100). c-KIT mRNA was evaluated by qRT-PCR in 34 frozen samples from AC Camargo Hospital Biobank (17 tumoral and 17 non-tumoral samples) using TaqMan probes–Applied Biosystems [Hs00174029_m1]. HPV genotyping was assessed in 103 samples using Linear Array® HPV Genotyping Test kit (Roche Molecular Diagnostics, Basel, Switzerland). All results obtained were correlated with clinical and pathological data of the patients. Results c-KIT protein was positive by immunohistochemistry in 70.5% of the cases and this was associated with a higher global survival (p = 0.007), a higher recurrence-free survival (p < 0.0001), an absence of associated lesions (p = 0.001), lymph node metastasis (p = 0.0053), and HPV infection (p = 0.034). Furthermore, c-KIT mRNA quantitation revealed higher levels of transcripts in normal samples compared to tumor samples (p = 0,0009). Conclusions Our findings indicate that those vulvar tumors staining positively for c-KIT present better prognosis. Thus, positivity of c-KIT as evaluated by IHC may be a good predictor for use of more conservative

  4. Prognostic investigations of B7-H1 and B7-H4 expression levels as independent predictor markers of renal cell carcinoma.

    PubMed

    Safaei, Hamid Reza; Rostamzadeh, Ayoob; Rahmani, Omid; Mohammadi, Mohsen; Ghaderi, Omar; Yahaghi, Hamid; Ahmadi, Koroosh

    2016-06-01

    In order to evaluate the correlation of B7-H4 and B7-H1 with renal cell carcinoma (RCC), we analyzed B7-H1 and B7-H4 expressions and their clinical significance by immunohistochemical method. Our result indicated that B7-H4-positive staining was detected in 58.13 % of RCC tissues (25 tissues tumors), and there were 18 tissues of patients without detectable B7-H4. Furthermore, 21 cases (48.83 %) were B7-H1-positive. Positive tumor expressions of B7-H4 and B7-H1 were markedly related to advanced TNM stage (P = 0.001; P = 0.014), high grade (P = 0.001; P = 002), and larger tumor size (P = 0.002; P = 024) in RCC tissues than patients with B7-H4-negative and B7-H1-negative in RCC tissues. The patients with B7-H1 and B7-H4-positive expressions were found to be markedly correlated with the overall survival of the patients (P < 0.05) and tended to have an increased risk of death when compared with negative expression groups. Univariate analysis showed that B7-H4 and B7-H1 expressions, TNM stage, high grade, and tumor size were significantly related to the prognosis of RCC. Furthermore, multivariate analysis showed that B7-H4 and B7-H1 expressions decreased overall survival. The adjusted HR for B7-H1 was 2.83 (95 % CI 1.210-2.971; P = 0.031) and also was 2.918 (95 % CI 1.243-3.102; P = 0.006) for B7-H4 that showed these markers were independent prognostic factors in RCC patients. The expressions of B7-H1 and B7-H4 in RCC patients indicate that these markers may be as a predictor of tumor development and death risk. Further investigations can be helpful to confirm B7-H1 and B7-H4 roles as an independent predictor of clinical RCC outcome. PMID:26687644

  5. Prognostic significance of serum insulin-like growth factor-1 in patients with hepatocellular carcinoma following transarterial chemoembolization

    PubMed Central

    LIU, SHENG; LIU, YANHUA; JIANG, XUEWEN

    2016-01-01

    Insulin-like growth factor-1 (IGF-1) is an effective survival factor that is involved in the development and progression of various tumors. The aim of the present study was to investigate whether baseline serum IGF-1 levels are associated with time to progression (TTP) and overall survival (OS) in patients with hepatocellular carcinoma (HCC) who have undergone transarterial chemoembolization (TACE). A total of 145 patients with HCC who underwent TACE as an initial treatment were enrolled in the study. Baseline serum IGF-1 levels were detected using enzyme-linked immunosorbent assay (ELISA) kits. The patients were followed up for a median follow-up period of 47 months (range, 10.6–69.3 months). During the follow-up, 98 patients (76.6%) experienced disease progression and 59 patients (46.1%) succumbed. The serum IGF-1 level was found to be significantly associated with hepatitis infection status, Child-Pugh class, bilirubin level, tumor size and nodularity, vascular invasion and the Barcelona Clinic Liver Cancer (BCLC) stage. Multivariate analysis was conducted, which indicated that BCLC stage, vascular invasion and serum IGF-1 were independent risk factors for disease progression. When clinical factors were examined as potential independent risk factors for OS, only advanced BCLC stage and low serum IGF-1 levels were found to be significantly associated with poorer OS. These results suggest that serum IGF-1 may serve as a predictor of the prognosis of patients with HCC undergoing TACE. PMID:26893654

  6. Prevalence and Prognostic Significance of Hyponatremia in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Data from the Akershus Cardiac Examination (ACE) 2 Study

    PubMed Central

    Brynildsen, Jon; Høiseth, Arne Didrik; Følling, Ivar; Brekke, Pål H.; Christensen, Geir; Hagve, Tor-Arne; Verbalis, Joseph G.; Omland, Torbjørn; Røsjø, Helge

    2016-01-01

    Background Hyponatremia is prevalent and associated with mortality in patients with heart failure (HF). The prevalence and prognostic implications of hyponatremia in acute exacerbation of chronic obstructive pulmonary (AECOPD) have not been established. Method We included 313 unselected patients with acute dyspnea who were categorized by etiology of dyspnea according to established guidelines (derivation cohort). Serum Na+ was determined on hospital admission and corrected for hyperglycemia, and hyponatremia was defined as [Na+]<137 mmol/L. Survival was ascertained after a median follow-up of 816 days and outcome was analyzed in acute HF (n = 143) and AECOPD (n = 83) separately. Results were confirmed in an independent AECOPD validation cohort (n = 99). Results In the derivation cohort, median serum Na+ was lower in AECOPD vs. acute HF (138.5 [135.9–140.5] vs. 139.2 [136.7–141.3] mmol/L, p = 0.02), while prevalence of hyponatremia (27% [22/83] vs. 20% [29/143], p = 0.28) and mortality rate (42% [35/83] vs. 46% [66/143], p = 0.56) were similar. By univariate Cox regression analysis, hyponatremia was associated with increased mortality in acute HF (HR 1.85 [95% CI 1.08, 3.16], p = 0.02), but not in AECOPD (HR 1.00 [0.47, 2.15], p = 1.00). Analogous to the results of the derivation cohort, hyponatremia was prevalent also in the AECOPD validation cohort (25% [25/99]), but not associated with mortality. The diverging effect of hyponatremia on outcome between AECOPD and acute HF was statistically significant (p = 0.04). Conclusion Hyponatremia is prevalent in patients with acute HF and AECOPD, but is associated with mortality in patients with acute HF only. PMID:27529844

  7. Prognostic significance of beta-blocker up-titration in conjunction with cardiac resynchronization therapy in heart failure management.

    PubMed

    Nabeta, Takeru; Inomata, Takayuki; Iida, Yuichiro; Ikeda, Yuki; Iwamoto-Ishida, Miwa; Ishii, Shunsuke; Naruke, Takashi; Mizutani, Tomohiro; Shinagawa, Hisahito; Koitabashi, Toshimi; Takeuchi, Ichiro; Ako, Junya

    2016-07-01

    Clinical practice guidelines emphasize that optimal pharmacotherapy, including beta-blockers (BB), is a prerequisite before receiving cardiac resynchronization therapy (CRT) in eligible patients with heart failure (HF). However, the optimal dose of BB before CRT implantation cannot be tolerated in a number of patients. Sixty-three consecutive patients who underwent CRT in 2006-2013 were retrospectively investigated. Before receiving CRT, BB could not be introduced in 20 patients (32 %); the daily carvedilol-equivalent dose in other 43 patients was 5.6 ± 7.0 mg because of significant HF and bradycardia. After receiving CRT, BB could be introduced in almost all patients (n = 61, 97 %), and the daily BB dose increased from 5.6 ± 7.0 to 13.2 ± 7.8 mg (P < 0.001). Multivariate analysis indicated that the change of BB dose after CRT was independently associated with improved left ventricular end-systolic volume (LVESV) [β = -0.36; 95 % confidence interval (CI) -2.13 to -0.45; P < 0.01] after 6-months follow-up. Furthermore, Cox proportional hazard analysis also showed that the change in the BB dose (hazard ratio, 0.92; 95 % CI, 0.87-0.98; P < 0.01) as well as the New York Heart Association functional classification was an independent predictor of cardiac events. After initiating CRT, BB therapy can be introduced and up-titrated in intolerant HF patients. The up-titrated dose of BB after CRT was an independent predictor for the improvement of LVESV and HF prognosis. PMID:26253941

  8. Functional activity maps based on significance measures and Independent Component Analysis.

    PubMed

    Martínez-Murcia, F J; Górriz, J M; Ramírez, J; Puntonet, C G; Illán, I A

    2013-07-01

    The use of functional imaging has been proven very helpful for the process of diagnosis of neurodegenerative diseases, such as Alzheimer's Disease (AD). In many cases, the analysis of these images is performed by manual reorientation and visual interpretation. Therefore, new statistical techniques to perform a more quantitative analysis are needed. In this work, a new statistical approximation to the analysis of functional images, based on significance measures and Independent Component Analysis (ICA) is presented. After the images preprocessing, voxels that allow better separation of the two classes are extracted, using significance measures such as the Mann-Whitney-Wilcoxon U-Test (MWW) and Relative Entropy (RE). After this feature selection step, the voxels vector is modelled by means of ICA, extracting a few independent components which will be used as an input to the classifier. Naive Bayes and Support Vector Machine (SVM) classifiers are used in this work. The proposed system has been applied to two different databases. A 96-subjects Single Photon Emission Computed Tomography (SPECT) database from the "Virgen de las Nieves" Hospital in Granada, Spain, and a 196-subjects Positron Emission Tomography (PET) database from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Values of accuracy up to 96.9% and 91.3% for SPECT and PET databases are achieved by the proposed system, which has yielded many benefits over methods proposed on recent works. PMID:23660005

  9. The prognostic significance of β-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: β-catenin predicts overall survival.

    PubMed

    Schneider, Sven; Thurnher, Dietmar; Seemann, Rudolf; Brunner, Markus; Kadletz, Lorenz; Ghanim, Bahil; Aumayr, Klaus; Heiduschka, Gregor; Lill, Claudia

    2016-05-01

    Minor salivary gland carcinoma is a rare and heterogeneous type of cancer. Molecular prognostic and predictive markers are sparse. The aim of this study was to identify new prognostic and predictive markers in minor salivary gland carcinoma. 50 tissue samples of carcinomas of the minor salivary glands (adenoid cystic carcinoma n = 23, mucoepidermoid carcinoma n = 12, adenocarcinoma n = 10, carcinoma ex pleomorphic adenoma n = 2, salivary duct carcinoma n = 1, clear cell carcinoma n = 1, basal cell carcinoma n = 1) were immunohistochemically stained for β-catenin, cyclin D1 and PIN1. Expression patterns were analyzed and correlated to clinical outcome of 37 patients with complete clinical data. High expression of membranous β-catenin was linked to significantly better overall survival in patients with adenoid cystic carcinoma (log rank test, χ (2) = 13.3, p = .00397, Bonferroni corrected p = .024). PIN1 and cyclin D1 did not show any significant correlation to patients' clinical outcome. Expression of β-catenin in adenoid cystic carcinoma of the minor salivary glands significantly correlates with better overall survival. Hence, evaluation of β-catenin might serve as a clinical prognostic marker. PMID:25801951

  10. Tumor-promoting function and prognostic significance of the RNA-binding protein T-cell intracellular antigen-1 in esophageal squamous cell carcinoma

    PubMed Central

    Fujita, Yuji; Naruto, Takuya; Kohmoto, Tomohiro; Miyakami, Yuko; Watanabe, Miki; Kudo, Yasusei; Fujiwara, Hitoshi; Ichikawa, Daisuke; Otsuji, Eigo; Imoto, Issei

    2016-01-01

    T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC. PMID:26958940

  11. Infiltrating CD57+ inflammatory cells in head and neck squamous cell carcinoma: clinicopathological analysis and prognostic significance.

    PubMed

    Fraga, Carlos Alberto de Carvalho; de Oliveira, Marcos Vinícius Macedo; Domingos, Patrícia Luciana Batista; Botelho, Ana Cristina de Carvalho; Guimarães, André Luiz Sena; Teixeira-Carvalho, Andréa; Correa-Oliveira, Rodrigo; De Paula, Alfredo Maurício Batista

    2012-05-01

    This study investigated the immunodetection of CD57+ inflammatory cells in patients with head and neck squamous cell carcinoma (HNSCC) and its association with clinicopathological parameters and overall survival. Data collected from the morphological analysis and immunohistochemical reaction testing of archived HNSCC specimens (n=70) were statistically analyzed by bivariate and multivariate statistical testing at a significance level of P<0.05. The results indicate that CD57+ inflammatory cells predominate within the peritumoral stroma of HNSCC lesions and the existence of two significant relationships: between high CD57+ cell density and the development of a tumor of a large size [odds ratio (OR)=5.610, 95% confidence interval (CI)=1.516-20.763) and between high CD57+ cell density and the development of locoregional metastatic disease (OR=3.401, 95% CI=1.162-9.951). A significant difference in the rate of survival was detected only in HNSCC patients that presented large size tumors (OR=4.747, 95% CI=1.281-17.594). Together, these results suggest that although high CD57+ inflammatory cell density is associated with HNSCC lesions of greater clinical severity, the variable of cell density is not an independent predictor of HNSCC patient survival. Our findings also suggest that the relatively aggressive infiltration of CD57+ inflammatory cells in the peritumoral stroma of head and neck carcinomas may contribute to an ineffective locoregional antitumoral response. PMID:22505010

  12. The prognostic significance of STAT3 in invasive breast cancer: analysis of protein and mRNA expressions in large cohorts.

    PubMed

    Aleskandarany, Mohammed A; Agarwal, Devika; Negm, Ola H; Ball, Graham; Elmouna, Ahmed; Ashankyty, Ibraheem; Nuglozeh, Edem; Fazaludeen, Mohammad F; Diez-Rodriguez, Maria; Nolan, Christopher C; Tighe, Patrick J; Green, Andrew R; Ellis, Ian O; Rakha, Emad A

    2016-02-01

    Signal transducer and activator of transcription (STAT) transcription factors family are involved in diverse cellular biological functions. Reports regarding the prognostic impact of STAT3 expression in breast cancer (BC) are variable whether being a factor of poor or good prognosis. Immunohistochemical expression of phospho-STAT3 (pSTAT3) was studied in large series of invasive BC (n = 1270). pSTAT3 and STAT3 were quantified using reverse phase protein array (RPPA) on proteins extracted from macro-dissected FFPE tissues (n = 49 cases). STAT3 gene expression in the METABRIC cohort was also investigated. STAT3 gene expression prognostic impact was externally validated using the online BC gene expression data (n = 26 datasets, 4.177 patients). pSTAT3 was expressed in the nuclei and cytoplasm of invasive BC cells. Nuclear pSTAT3 overexpression was positively associated with smaller tumour size, lower grade, good NPI, negative lymphovascular invasion (LVI), ER+, PgR+, p53-, HER2-, and low Ki67LI and an improved breast cancer-specific survival (BCSS), independently of other factors. On RPPA, the mean pSTAT3 and STAT3 expressions were higher in ER+, PgR+, and smaller size tumours. Higher STAT3 transcripts in the METABRIC cohort were observed in cases with favourable prognostic criteria and as well as improved BCSS within the whole cohort, ER+ cohort with and without hormonal therapy, and ER- cohort including those who did not receive adjuvant chemotherapy. Pooled STAT3 gene expression data in the external validation cohort showed an association with improved patients' outcome (P < 0.001, HR = 0.84, 95 % CI 0.79-0.90). Results of this study suggest nuclear localisation of pSTAT3 as favourable prognostic marker in invasive BC, results re-enforced by analysis of STAT3 gene expression data. This good prognostic advantage was maintained in patients who received and who did not receive adjuvant therapy. Therefore, STAT3 could have context-dependent molecular roles of in BC

  13. A Cell Type Independent Binary Grading System Does Not Significantly Improve Endometrial Biopsy Interpretation.

    PubMed

    Nastic, Denis; Kahlin, Frida; Dahlstrand, Hanna; Carlson, Joseph W

    2016-05-01

    The revised International Federation of Gynecology and Obstetrics (FIGO) grading system is widely accepted as the standard in evaluating endometrial carcinoma on biopsy. Determination of tumor cell type [using the World Health Organization (WHO) diagnostic criteria] and grade (using FIGO) guides surgical approach. Several studies have highlighted discrepancies between biopsy and hysterectomy diagnosis. Recently, a binary grading system was proposed, yielding a low-risk and high-risk assessment but in a cell type independent (CTI) way. No study has assessed its utility in biopsy grading, a situation where this system may be particularly useful. Archived endometrial biopsies from 70 cases of endometrial carcinoma were graded by 3 independent observers using the WHO/FIGO and the CTI grading systems. The overall accuracy, interobserver agreement, and ease of use were assessed. This study found comparable substantial accuracy between the WHO/FIGO and CTI grading systems (κ=0.71 vs. κ=0.69), with the same setbacks in overgrading of 20.9% versus 25.6% of low-risk tumors. The CTI grading system was not superior to the WHO/FIGO grading system in accuracy of subtyping and grading and interobserver reproducibility. Although determination of cell type is difficult, it does not appear that the proposed CTI system confers any significant advantages over existing grading. PMID:26863477

  14. Prognostic and Clinicopathological Significance of Survivin Expression in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis.

    PubMed

    Xie, Yongpeng; Ma, Xin; Gu, Liangyou; Li, Hongzhao; Chen, Luyao; Li, Xintao; Gao, Yu; Fan, Yang; Zhang, Yu; Yao, Yuanxin; Zhang, Xu

    2016-01-01

    Previous studies have elevated the prognostic value of survivin in renal cell carcinoma (RCC). To increase statistical power and improve translation, we systematically searched PubMed, Web of Science, and Embase to identify relevant studies until December 2015 and conducted a standard meta-analysis. Based on the inclusion and exclusion criteria, a total of 12 studies, including 2051 patients, were eligible for further analysis. Results showed that high survivin expression in RCC was associated with poor OS (HR = 2.84, 95% CI 1.68-4.79), CSS (HR = 2.36, 95% CI 1.41-3.95), and PFS (HR = 2.20, 95% CI 1.58-3.08). Survivin expression was also correlated with TNM stage (RR = 2.75, 95% CI 2.21-3.44), pathological T stage (RR = 2.19, 95% CI 1.75-2.75), lymph node metastasis (RR = 2.28, 95% CI 1.61-3.25), distant metastasis (RR = 1.56, 95% CI 1.16-2.08), Fuhrman grade (RR = 2.81, 95% CI 2.29-3.45), tumor size (RR = 1.49, 95% CI 1.24-1.78). Our study suggested that survivin was a prognostic marker in RCC. High survivin expression was correlated with poor prognosis and more advanced clinicopathological features, and it could serve as a biomarker for disease management. PMID:27411378

  15. Study of the biological and prognostic significance of the antigen CaMBr8 on breast carcinoma.

    PubMed Central

    Facheris, P.; Perrone, F.; Ménard, S.; Andreola, S.; Bazzini, P.; Bufalino, R.; Canevari, S.; Cascinelli, N.; Colzani, E.; Di Fronzo, G.

    1992-01-01

    We previously reported that the expression on the primary tumour of the antigen CaMBr8 was related to a short survival, attributable either to higher tumour aggressiveness or a poor response to oophorectomy. To further verify the CaMBr8 prognostic value, we analysed retrospectively 862 breast cancer patients with a 19 year follow-up. In this series, CaMBr8 expression was found to be associated to some negative prognostic factors (premenopausal status, lymphnode invasion, a high number of mitosis and HER-2/neu oncoprotein expression), but had no influence on the patients' survival. Direct association with a poor prognosis was only evident in patients with lobular or mixed breast carcinoma, which however represent only a small fraction of the total breast cancers. Another possibility was that CaMBr8 could identify a subgroup of patients which did not respond to hormone therapy. To verify this hypothesis we evaluated on a second series of 116 patients the relationship between CaMBr8 expression and hormone-receptor levels. A negative association emerged which was also observed in vitro in the human breast cancer line MCF-7 treated with Sodium Butyrate, a differentiation inducer, which reduced hormone-receptor levels and increased CaMBr8 expression. In conclusion, the longer survival of CaMBr8 negative tumour patients observed in the initial study, was probably related to a better response to oophorectomy, due to the hormone-receptor level of their tumours. PMID:1558805

  16. Prognostic Significance of Combination of Preoperative Platelet Count and Neutrophil-Lymphocyte Ratio (COP-NLR) in Patients with Non-Small Cell Lung Cancer: Based on a Large Cohort Study

    PubMed Central

    Zhang, Hua; Zhang, Lianmin; Zhu, Kaikai; Shi, Bowen; Yin, Yuesong; Zhu, Jinfang; Yue, Dongsheng; Zhang, Bin; Wang, Changli

    2015-01-01

    Introduction The aim of this study was to investigate the prognostic significance of the combination of the preoperative platelet count and neutrophil-lymphocyte ratio (COP-NLR) for predicting postoperative survival of patients undergoing complete resection for non-small cell lung cancer (NSCLC). Methods The preoperative COP-NLR was calculated on the basis of data obtained.Patients with both an increased platelet count (>30.0×104 mm-3) and an elevated NLR (>2.3) were assigned a score of 2, and patients with one or neither were assigned as a score of 1 or 0, respectively. Results A total of 1238 NSCLC patients were enrolled in this analysis. Multivariate analysis using the 15 clinicolaboratory variables selected by univariate analyses demonstrated that the preoperative COP-NLR was an independent prognostic factor for DFS (HR: 1.834, 95%CI: 1.536 to 2.200, P<0.001) and OS (HR: 1.810, 95%CI: 1.587 to 2.056, P<0.001). In sub-analyses by tumor stage (I, II, IIIA), a significant association was found between DFS and OS and level of COP-NLR in each subgroup (P<0.001, P=0.002, P<0.001 for DFS, respectively; P<0.001, P=0.001, P<0.001 for OS). When the subgroup of patients with high-risk COP-NLR (score of 2) was analyzed, no benefit of adjuvant chemotherapy could be found (P=0.237 for DFS and P=0.165 for OS). Conclusions The preoperative COP-NLR is able to predict the prognosis of patients with NSCLC and divide these patients into three independent groups before surgery. Our results also demonstrate that high-risk patients based on the COP-NLR do not benefit from adjuvant chemotherapy. Independent validation of our findings is warranted. PMID:25950176

  17. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study.

    PubMed

    Xu-Monette, Zijun Y; Wu, Lin; Visco, Carlo; Tai, Yu Chuan; Tzankov, Alexander; Liu, Wei-min; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Zhao, X Frank; Choi, William W L; Zhao, Xiaoying; van Krieken, J Han; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J M; Zhou, Fan; Kahl, Brad S; Winter, Jane N; Xu, Wei; Li, Jianyong; Go, Ronald S; Li, Yong; Piris, Miguel A; Møller, Michael B; Miranda, Roberto N; Abruzzo, Lynne V; Medeiros, L Jeffrey; Young, Ken H

    2012-11-01

    TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. In the present study of a large cohort of DLBCL patients treated with rituximab plus CHOP (R-CHOP), we show that those with TP53 mutations had worse overall and progression-free survival compared with those without. Unlike earlier studies of patients treated with CHOP, TP53 mutation has predictive value for R-CHOP-treated patients with either the germinal center B-cell or activated B-cell DLBCL subtypes. Furthermore, we identified the loop-sheet-helix and L3 motifs in the DNA-binding domain to be the most critical structures for maintaining p53 function. In contrast, TP53 deletion and loss of heterozygosity did not confer worse survival. If gene mutation data are not available, immunohistochemical analysis showing > 50% cells expressing p53 protein is a useful surrogate and was able to stratify patients with significantly different prognoses. We conclude that assessment of TP53 mutation status is important for stratifying R-CHOP-treated patients into distinct prognostic subsets and has significant value in the design of future therapeutic strategies. PMID:22955915

  18. HDAC isoenzyme expression is deregulated in chronic lymphocytic leukemia B-cells and has a complex prognostic significance

    PubMed Central

    Van Damme, Michaël; Crompot, Emerence; Meuleman, Nathalie; Mineur, Philippe; Bron, Dominique; Lagneaux, Laurence; Stamatopoulos, Basile

    2012-01-01

    Histone deacetylases (HDACs) play a crucial role in chromatin structure and, consequently, gene expression. Their deregulation has been reported in various cancers. We performed a complete and comprehensive study of the expression of 18 HDACs (including Sirtuin; SIRT) by real-time PCR in a cohort of 200 chronic lymphocytic leukemia (CLL) patients with a median follow-up of 77 mo, and compared it with the results obtained from normal B cells. We also compared HDAC expression at diagnosis and after relapse. We observed significant deregulation (mostly upregulation) of HDACs in CLL. In terms of clinical significance, only HDAC6 was significantly correlated with treatment-free survival (TFS), whereas HDAC3 and SIRT2, 3 and 6 were correlated with overall survival (OS). A multivariate Cox regression stepwise analysis indicated that HDAC6, 7 and 10 and SIRT3 were TFS independent predictors. Interestingly, poor prognosis was associated with an overexpression of HDAC7 and 10 but an underexpression of HDAC6 and SIRT3. Therefore, these factors were combined in a TFS score: patients with a score of 0–1–2, 3 and 4 had a median TFS of 107, 57 and 26 mo, respectively (HR = 4.03, p < 0.0001). For OS, SIRT5 and 6 allowed stratification into 3 groups, with a median OS of > 360, 237 and 94 mo (HR = 6.38, p < 0.0001). However, we could not find statistical differences in HDAC expression after relapse. These results, validated by a 5-fold cross-validation, highlight the complex impact of HDAC expression in CLL clinical course. PMID:23108383

  19. Expression of MAGE-A1, -A9, -A11 in laryngeal squamous cell carcinoma and their prognostic significance: a retrospective clinical study.

    PubMed

    Liu, Shenghui; Sang, Meixiang; Xu, Yuru; Gu, Lina; Liu, Fei; Shan, Baoen

    2016-05-01

    Conclusion The melanoma-associated antigens A1, -A9, -A11 (MAGE-A1, -A9, -A11) are relatively tumor-specific in laryngeal squamous cell carcinoma (LSCC), and could be ideal antigens for LSCC immunotherapy. In addition, MAGE-A9 probably is a poor prognostic marker for LSCC patients. Objective The MAGE-A family belongs to Cancer/testis antigens (CTA). However, the expression pattern of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC is still unclear. This study aims to evaluate the expression and possible prognostic role of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC patients. Methods The expression of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC specimens was investigated by immunohistochemistry, and the association of their expression and the clinical parameters and the survival of LSCC patients were analyzed by chi-square test, Kaplan-Meier survival and Cox regression analysis. Results The expression rates of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC were 54.7%, 46.2%, and 51.9%, respectively. The expression of MAGE-A1, MAGE-A9, and MAGE-A11 in LSCC was correlated with clinical stage, lymph node metastasis, and tumor size. The overall survival of LSCC patients with positive MAGE-A1, MAGE-A9, or MAGE-A11 expression was lower than the patients without MAGE-A1, MAGE-A9, or MAGE-A11 expression. Cox's multivariable analysis showed that MAGE-A9 expression was an independently poor prognostic factor for LSCC patients. PMID:26766421

  20. Diagnostic investigations of DKK-1 and PDCD5 expression levels as independent prognostic markers of human chondrosarcoma.

    PubMed

    Zarea, Mojtaba; Mohammadian Bajgiran, Amirhossein; Sedaghati, Farnoush; Hatami, Negin; Taheriazam, Afshin; Yahaghi, Emad; Shakeri, Mohammadreza

    2016-07-01

    In this study, we investigated the expression levels of Dickkopf-1 (DKK-1) and programmed cell death 5 (PDCD5) by using quantitative real-time PCR and immunohistochemistry in patients with chondrosarcoma. The DKK-1 mRNA levels were significantly higher in chondrosarcoma when compared with the corresponding nontumor tissues (mean ± SD: 4.23 ± 1.54; 1.54 ± 0.87; P = 0.001). PDCD5 mRNA levels were remarkably deceased in tumor tissues when compared with corresponding nontumor tissues (mean ± SD: 1.94 ± 0.73; 5.42 ± 1.73; P = 0.001). The high and moderate DKK-1 expressions were observed for 60% of chondrosarcoma samples in comparison with 27.5% of corresponding nontumor tissues (P  =  0.001). Moreover, low expression of PDCD5 was found in 67.5% of the tumor tissues when compared with the nontumor tissues (32.5%; P = 0.002). The results of this study showed that high DKK-1 expression levels were strongly related to MSTS stage (P = 0.011) and the advancement of histological grade (P < 0.001). Furthermore, the PDCD5 expression levels were correlated with histological grade (P < 0.001), MSTS stage (P = 0.016), and distant metastasis (P = 0.001). Kaplan-Meier survival and log-rank survival showed that patients with high DKK-1 levels and low PDCD5 levels were correlated with shorter overall survival (log-rank test P < 0.001). PDCD5 levels, histological grade, and tumor stage were independent predictors of overall survival. In conclusion, DKK-1 and PDCD5 can be independent predictors of overall survival in patients suffering from chondrosarcoma. © 2016 IUBMB Life, 68(7):597-601, 2016. PMID:27255549

  1. Clinicopathological and prognostic significance of Oct-4 expression in patients with non-small cell lung cancer: a systematic review and meta-analysis

    PubMed Central

    Li, Shuang-Jiang; Huang, Jian; Zhou, Xu-Dong; Zhang, Wen-Biao; Lai, Yu-Tian

    2016-01-01

    Background Octamer-binding transcription factor 4 (Oct-4) has been identified to participate in the tumorigenicity and malignancy of non-small cell lung cancer (NSCLC). However, its definite prognostic roles in NSCLC still remain a debate. Therefore, we conducted this meta-analysis to evaluate the prognostic value of Oct-4 expression in NSCLC and its relationship to some major clinicopathological characteristics. Methods A comprehensive literature retrieval was performed in PubMed, EMBASE and the Web of Science to identify the full-text articles that met our eligibility criteria. Odds ratio (OR) with 95% confidence interval (CI) severed as the summarized statistics for clinicopathological assessments, and hazard ratio (HR) with 95% CI served as the summarized statistics for prognostic assessments. Q-test and I2-statistic were used to evaluate the level of heterogeneity. Potential publication bias was detected by both Begg’s test and Egger’s test. Results There were 16 retried articles with 1,363 NSCLC cases included into this meta-analysis. Oct-4 expression was found to be significantly associated with the unfavorable outcomes for differentiation degree (OR: 3.065; 95% CI: 1.568–5.957; P=0.001), TNM stage (OR: 3.695; 95% CI: 2.252–6.063; P<0.001) and lymphatic metastasis (OR: 2.372; 95% CI: 1.504–3.742; P<0.001), but not associated with the histological subtypes, gender, age and smoking status. Oct-4 expression was also significantly associated with the poor prognosis of NSCLC (HR: 3.030; 95% CI: 2.283–4.021; P<0.001). The prognostic roles of Oct-4 expression in NSCLC still remained statistically reliable in the subgroups stratified by statistical analysis, patients’ origins, positively-stained sites and histological subtypes. Conclusions Our meta-analysis indicates that Oct-4 can serve as a strong biomarker predicting the poor clinicopathological and prognostic characteristics of NSCLC. More high-quality studies based on a large sample size will be

  2. Prognostic and Clinicopathological Significance of Survivin Expression in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis

    PubMed Central

    Xie, Yongpeng; Ma, Xin; Gu, Liangyou; Li, Hongzhao; Chen, Luyao; Li, Xintao; Gao, Yu; Fan, Yang; Zhang, Yu; Yao, Yuanxin; Zhang, Xu

    2016-01-01

    Previous studies have elevated the prognostic value of survivin in renal cell carcinoma (RCC). To increase statistical power and improve translation, we systematically searched PubMed, Web of Science, and Embase to identify relevant studies until December 2015 and conducted a standard meta-analysis. Based on the inclusion and exclusion criteria, a total of 12 studies, including 2051 patients, were eligible for further analysis. Results showed that high survivin expression in RCC was associated with poor OS (HR = 2.84, 95% CI 1.68–4.79), CSS (HR = 2.36, 95% CI 1.41–3.95), and PFS (HR = 2.20, 95% CI 1.58–3.08). Survivin expression was also correlated with TNM stage (RR = 2.75, 95% CI 2.21–3.44), pathological T stage (RR = 2.19, 95% CI 1.75–2.75), lymph node metastasis (RR = 2.28, 95% CI 1.61–3.25), distant metastasis (RR = 1.56, 95% CI 1.16–2.08), Fuhrman grade (RR = 2.81, 95% CI 2.29–3.45), tumor size (RR = 1.49, 95% CI 1.24–1.78). Our study suggested that survivin was a prognostic marker in RCC. High survivin expression was correlated with poor prognosis and more advanced clinicopathological features, and it could serve as a biomarker for disease management. PMID:27411378

  3. Long-term prognostic significance of admission plateletcrit values in patients with non-ST elevation myocardial infarction.

    PubMed

    Gul, Mehmet; Uyarel, Huseyin; Akgul, Ozgur; Akkaya, Emre; Surgit, Ozgur; Cakmak, Huseyin Altug; Pusuroglu, Hamdi; Yakisan, Turab; Aslan, Serkan; Eksik, Abdurrahman

    2016-09-01

    The plateletcrit has been investigated as a new predictor of cardiovascular risk. The objective of our study was to investigate the role of admission plateletcrit in predicting long-term cardiovascular mortality in patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI). We enrolled 296 patients with NSTEMI (mean age 59.2 ± 11.8 years; 228 men, 68 women) in this study. The study population was divided into tertiles on the basis of admission plateletcrit values. A high plateletcrit (n = 98) was defined as a value in the upper third tertile (plateletcrit >0.23), and a low plateletcrit (n = 198) was defined as any value in the lower two tertiles (plateletcrit ≤0.23). The median follow-up time was 38 months. In multivariate analyses, a significant association was noted between high plateletcrit values and the adjusted risk of long-term mortality (odds ratio = 12.15, 95% confidence interval = 1.78-82.77; P < 0.001). In the Kaplan-Meier survival analysis, the long-term mortality rate was 20.4% in the high plateletcrit group versus 4.5% in the low plateletcrit group (P < 0.001). Long-term major advanced cardiac events (MACE), hospitalization for heart failure and reinfarction were significantly higher in patients with high plateletcrit. Admission plateletcrit is a strong and independent predictor of long-term cardiovascular mortality in patients with NSTEMI. PMID:26820228

  4. High-mobility group AT-hook protein 2 expression and its prognostic significance in MGMT methylated and unmethylated glioblastoma.

    PubMed

    Schwarm, Frank P; Uhle, Florian; Schänzer, Anne; Acker, Till; Stein, Marco; Reinges, Marcus H T; Weischer, Cornelia; Weigand, Marcus A; Uhl, Eberhard; Kolodziej, Malgorzata A

    2016-04-01

    High-mobility group AT-hook protein 2 (HMGA 2) is a transcription factor associated with malignancy and poor prognosis in a variety of human cancers. We correlated HMGA 2 expression with clinical parameters, survival, and O-6-methylguanine-DNA methyltransferase methylation status (MGMT) in glioblastoma patients. HMGA 2 expression was determined by performing quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in 44 glioblastoma patients and 5 non-tumorous brain specimens as controls. Gene expression levels of MGMT methylated vs. unmethylated patients, and gene expression levels between patient groups, both for qPCR and IHC data were compared using the Mann-Whitney U test. The relationship between HMGA 2 expression, progression-free survival and overall survival was analyzed using the Kaplan-Meier method and the log-rank test. P-values of <0.05 were considered statistically significant throughout the analyses. The mean age of patients at diagnosis was 57.4 ± 15.7 years, and the median survival was 16 months (SE 2.8; 95% CI, 10.6-21.4). HMGA 2 gene expression was significantly higher in glioblastoma compared to normal brain tissue on qPCR (mean, 0.35; SD, 0.27 vs. 0.03, SD, 0.05) and IHC levels (IRS mean, 17.21; SD, 7.43 vs. 3.20; SD, 1.68) (p=0.001). Survival analysis revealed that HMGA 2 overexpression was associated with a shorter progression-free and overall survival time in patients with methylation (n=24). The present study shows a tendency that HMGA 2 overexpression correlates with a poor prognosis of glioblastoma patients independent of MGMT methylation status. The results suggest that HMGA 2 could play an important role in the treatment of glioblastoma and could have a function in prognosis of this type of cancer. PMID:26892260

  5. Brachial-to-ankle pulse wave velocity as an independent prognostic factor for ovulatory response to clomiphene citrate in women with polycystic ovary syndrome

    PubMed Central

    2014-01-01

    Background Polycystic ovary syndrome (PCOS) has a risk for cardiovascular disease. Increased arterial stiffness has been observed in women with PCOS. The purpose of the present study was to investigate whether the brachial-to-ankle pulse wave velocity (baPWV) is a prognostic factor for ovulatory response to clomiphene citrate (CC) in women with PCOS. Methods This study was a retrospective cohort study of 62 women with PCOS conducted from January 2009 to December 2012 at the university hospital, Yamagata, Japan. We analyzed 62 infertile PCOS patients who received CC. Ovulation was induced by 100 mg CC for 5 days. CC non-responder was defined as failure to ovulate for at least 2 consecutive CC-treatment cycles. The endocrine, metabolic, and cardiovascular parameters between CC responder (38 patients) and non-responder (24 patients) groups were analyzed. Results In univariate analysis, waist-to-hip ratio, level of free testosterone, percentages of patients with dyslipidemia, impaired glucose tolerance, and diabetes mellitus, blood glucose and insulin levels at 60 min and 120 min, the area under the curve of glucose and insulin after 75-g oral glucose intolerance test, and baPWV were significantly higher in CC non-responders compared with responders. In multivariate logistic regression analysis, both waist-to-hip ratio (odds ratio, 1.77; 95% confidence interval, 2.2–14.1; P = 0.04) and baPWV (odds ratio, 1.71; 95% confidence interval, 1.1–2.8; P = 0.03) were independent predictors of ovulation induction by CC in PCOS patients. The predictive values of waist-to-hip ratio and baPWV for the CC resistance in PCOS patients were determined by the receiver operating characteristic curves. The area under the curves for waist-to-hip ratio and baPWV were 0.76 and 0.77, respectively. Setting the threshold at 0.83 for waist-to-hip ratio offered the best compromise between specificity (0.65) and sensitivity (0.84), while the setting the threshold at 1,182 cm/s for

  6. Twelve-Month Prostate-Specific Antigen Values and Perineural Invasion as Strong Independent Prognostic Variables of Long-Term Biochemical Outcome After Prostate Seed Brachytherapy

    SciTech Connect

    Ding, William; Lee, John; Chamberlain, David; Cunningham, James; Yang Lixi; Tay, Jonathan

    2012-11-15

    Purpose: To determine whether post-treatment prostate-specific antigen (ptPSA) values at 12 months and other clinical parameters predict long-term PSA relapse-free survival (PRFS) following prostate seed brachytherapy. Methods and Materials: Records of 204 hormone-naieve patients with localized adenocarcinoma of the prostate treated at St. Mary's Regional Medical Center in Reno, NV, and at Carson Tahoe Regional Medical Center in Carson City, NV, between 1998 and 2003, using I-125 or Pd-103 seed brachytherapy, were retrospectively analyzed. Treatment planning was done using a preplanned, modified peripheral loading technique. A total of 185 of 204 patients had PSA records at 12 months after implant. Variables included were age, initial pretreatment PSA, Gleason score, T stage, National Comprehensive Cancer Network (NCCN) risk group (RG), perineural invasion (PNI), external beam boost, dose, and ptPSA levels at 12 months with cutpoints at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml. Results: Median follow-up was 80 months, and median age was 69 years. The numbers of patients stratified by NCCN low, intermediate, and high RG were 110:65:10, respectively. Monotherapy and boost prescription doses were 145 Gy and 110 Gy for I-125, and 125 Gy and 100 Gy for Pd-103 seeds, respectively. The median dose (D90) was 95.4% of the prescribed dose. The 5-year PRFS at the 12-months ptPSA levels of {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml were 98.5%, 85.7%, 61.5%, and 22.2%, respectively. The 10-year PRFS at the 12-months ptPSA levels of {<=}1 and 1.01 to 2.00 ng/ml were 90.5% and 85.7%, respectively. In multivariate analysis, both ptPSA and PNI were significant independent predictors of PRFS. Hazard ratios (HR) for ptPSA levels at {<=}1, 1.01 to 2.00, 2.01 to 3.00, and >3.00 ng/ml at 12 months were 1, 4.96, 27.57, and 65.10, respectively. PNI had an HR of 6.1 (p = 0.009). Conclusions: Presence of PNI and ptPSA values at 12 months are strong prognostic variables for

  7. c-MYC Copy-Number Gain Is an Independent Prognostic Factor in Patients with Colorectal Cancer

    PubMed Central

    Lee, Kyu Sang; Kwak, Yoonjin; Nam, Kyung Han; Kim, Duck-Woo; Kang, Sung-Bum; Choe, Gheeyoung; Kim, Woo Ho; Lee, Hye Seung

    2015-01-01

    Background The aim of this study was to determine the incidence and clinicopathological significance of c-MYC gene copy-number (GCN) gain in patients with primary colorectal cancer (CRC). Methods The c-MYC GCN was investigated in 367 consecutive CRC patients (cohort 1) by using dual-color silver in situ hybridization. Additionally, to evaluate regional heterogeneity, we examined CRC tissue from 3 sites including the primary cancer, distant metastasis, and lymph-node metastasis in 152 advanced CRC patients (cohort 2). KRAS exons 2 and 3 were investigated for mutations. Results In cohort 1, c-MYC gene amplification, defined by a c-MYC:centromere of chromosome 8 ratio ≥ 2.0, was detected in 31 (8.4%) of 367 patients. A c-MYC GCN gain, defined by ≥ 4.0 c-MYC copies/nucleus, was found in 63 (17.2%) patients and was associated with poor prognosis (P = 0.015). Multivariate Cox regression analysis showed that the hazard ratio for c-MYC GCN gain was 2.35 (95% confidence interval, 1.453–3.802; P < 0.001). In a subgroup of stage II-III CRC patients, c-MYC GCN gain was significantly associated with poor prognosis by univariate (P = 0.034) and multivariate (P = 0.040) analyses. c-MYC protein overexpression was observed in 201 (54.8%) out of 367 patients and weakly correlated with c-MYC GCN gain (ρ, 0.211). In cohort 2, the c-MYC genetic status was heterogenous in advanced CRC patients. Discordance between GCN gain in the primary tumor and either distant or lymph-node metastasis was 25.7% and 30.4%, respectively. A similar frequency for c-MYC GCN gain and amplification was observed in CRC patients with both wild-type and mutated KRAS. Conclusions c-MYC GCN gain was an independent factor for poor prognosis in consecutive CRC patients and in the stage II-III subgroup. Our findings indicate that the status of c-MYC may be helpful in predicting the patients’ outcome and for managing CRC patients. PMID:26426996

  8. Prognostic and Clinicopathological Significance of Downregulated E-Cadherin Expression in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis

    PubMed Central

    Xian, Lei

    2014-01-01

    Background Many studies have investigated the prognostic role of E-cadherin in patients with NSCLC; however, the result still remains inconclusive. An up-to data system review and meta-analysis was necessary to give a comprehensive evaluation of prognostic role of E-cadherin in NSCLC. Methods Eligible studies were searched in Pubmed, Embase and Web of Science databases. The inclusion criteria were studies that assessed the relationship between E-cadherin expression detected by immunohistochemistry (IHC) and the prognosis or clinicopathological features in patients with NSCLC. Subgroup analysis according to race, percentage of reduced/negative E-cadherin expression, histological type, and sample size were also conducted. Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association. Results A total of 29 studies including 4010 patients were qualified for analysis. The analysis suggested that downregulated E-cadherin expression was significant associated with unfavorable overall survival (OS) and disease-free survival/progression-free survival (DFS/PFS) in patients with NSCLC. Subgroup analysis by race, percentage of reduced/negative E-cadherin expression, sample size also found the significant association in OS. When only the stage I NSCLC were considered, downregulated E-cadherin expression still had an unfavorable impact on OS. Additionally, downregulated E-cadherin expression was significantly associated with differentiation grade, lymphnode metastasis, vascular invasion, and TNM stage. Conclusion Downregulated E-cadherin expression detected by IHC seems to correlate with tumour progression and could serve as an important prognostic factor in patients with NSCLC. PMID:24978478

  9. Lack of prognostic significance of epidermal growth factor receptor and the oncoprotein p185HER-2 in patients with systemically untreated non-small-cell lung cancer: an immunohistochemical study on cryosections.

    PubMed Central

    Pfeiffer, P.; Clausen, P. P.; Andersen, K.; Rose, C.

    1996-01-01

    The prognostic role of the epidermal growth factor receptor (EGFR) and the related receptor p185HER-2 in lung cancer is as yet undefined. We investigated the immunohistochemical expression of EGFR (monoclonal antibody R1; Amersham) and p185HER-2 (polyclonal antibody A485; Dako) in cryosections. A total of 186 unselected and systemically untreated patients with non-small-cell lung cancer (NSCLC) diagnosed and treated at Odense University Hospital, Denmark, were included. Median follow-up period was 66 months. EGFR and p185HER-2 was highly expressed in 55% and 26% of cases respectively. Expression of EGFR was independent of p185HER-2 expression. The expression of EGFR was higher in squamous cell carcinomas whereas the level of p185HER-2 staining was higher in adenocarcinomas. Expression of either or both receptors was not correlated with age, histological grading, stage and prognosis. We conclude that immunohistochemical detection of these growth factor receptors failed to demonstrate a prognostic significance in patients operated on for NSCLC. PMID:8679464

  10. Can Lightning Produce Significant Levels of Mass-Independent Oxygen Isotopic Fractionation in Nebular Dust?

    NASA Technical Reports Server (NTRS)

    Nuth, Joseph A.; Paquette, John A.; Farquhar, Adam

    2012-01-01

    Based on recent evidence that oxide grains condensed from a plasma will contain oxygen that is mass independently fractionated compared to the initial composition of the vapor, we present a first attempt to evaluate the potential magnitude of this effect on dust in the primitive solar nebula. This assessment relies on previous studies of nebular lightning to provide reasonable ranges of physical parameters to form a very simple model to evaluate the plausibility that lightning could affect a significant fraction of nebular dust and that such effects could cause a significant change in the oxygen isotopic composition of solids in the solar nebula over time. If only a small fraction of the accretion energy is dissipated as lightning over the volume of the inner solar nebula, then a large fraction of nebular dust will be exposed to lightning. If the temperature of such bolts is a few percent of the temperatures measured in terrestrial discharges, then dust will vaporize and recondense in an ionized environment. Finally, if only a small average decrease is assumed in the O-16 content of freshly condensed dust, then over the last 5 million years of nebular accretion the average delta O-17 of the dust could increase by more than 30 per mil. We conclude that it is possible that the measured " slope 1" oxygen isotope line measured in meteorites and their components represents a time-evolution sequence of nebular dust over the last several million years of nebular evolution O-16-rich materials formed first, then escaped further processing as the average isotopic composition of the dust graduaUy became increasingly depleted in O-16 .

  11. Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

    PubMed Central

    Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

    2016-01-01

    AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. RESULTS: The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers. PMID:26937145

  12. Combination of PLR, MLR, MWR, and Tumor Size Could Significantly Increase the Prognostic Value for Gastrointestinal Stromal Tumors.

    PubMed

    Feng, Fan; Tian, Yangzi; Liu, Shushang; Zheng, Gaozan; Liu, Zhen; Xu, Guanghui; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2016-04-01

    Systemic inflammation and immune response were associated with prognosis of tumors. However, data was limited due to the relatively low incidence of gastrointestinal stromal tumors (GISTs). The aim of the present study was to investigate the predictive value of preoperative peripheral blood cells in prognosis of GISTs.From September 2008 to July 2015, a total of 274 GIST patients in our department were enrolled in the present study. Clinicopathological features of GISTs were recorded. The association between preoperative peripheral blood cells and prognosis of GISTs were analyzed.Tumor location, tumor size, mitotic index, intratumoral necrosis, and National Institutes of Health (NIH) risk category were associated with prognosis of GISTs. High neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-white blood cell ratio (NWR), monocyte-to-white blood cell ratio (MWR) and low lymphocyte-to-white blood cell ratio (LWR) was associated with poor prognosis of GISTs (76.2% vs 83.7%, P = 0.010. 70.5% vs 98.7%, P = 0.000. 65.7% vs 96.4%, P = 0.004. 78.5% vs 82.5%, P = 0.044. 73.5% vs 97.8%, P = 0.004. 76.6% vs 83.6%, P = 0.012, respectively). However, tumor size was the only independent risk factor for prognosis according to multivariate analysis (P = 0.006). Tumor location, tumor size, mitotic index, and NIH risk category were significantly correlated with the above-mentioned parameters (all P < 0.05). The prognosis of GISTs with tumor size >5 cm, high MLR, high PLR, and high MWR was significantly lower than the remnant patients (P = 0.010).The peripheral blood routine test is convenient, reproducible, and inexpensive. High NLR, MLR, PLR, NWR, MWR, and low LWR were associated with poor prognosis of GISTs. The association between the above parameters and prognosis of GISTs may be attributed to their correlation with tumor size, mitotic index, and NIH risk category. The

  13. Prognostic significance of CCND1 (cyclin D1) overexpression in primary resected non-small-cell lung cancer.

    PubMed Central

    Betticher, D. C.; Heighway, J.; Hasleton, P. S.; Altermatt, H. J.; Ryder, W. D.; Cerny, T.; Thatcher, N.

    1996-01-01

    Amplification of the CCDN1 gene encoding cyclin D1 was examined by Southern blotting and multiplex polymerase chain reaction (PCR) and occurred in 8 of 53 patients (15%) with primary resected non-small-cell lung cancer (NSCLC). These tumours and 17 additional tumours with a normal gene copy number showed overexpression of cyclin D1 (25/53, 47%), as assessed by immunostaining using a monoclonal antibody. In 22/25 cases, cyclin D1 was localised in the cytoplasm, but some (7/25) had simultaneous nuclear staining. This result is in marked contrast to that reported in breast, hepatocellular and colorectal carcinoma studies where immunostaining was invariably nuclear. Examination of a restriction fragment length polymorphic (RFLP) site within the 3'untranslated region of the cDNA following reverse transcriptase (RT)-PCR (29/53 informative cases) showed a strong association between cytoplasmic staining and imbalance in allele-specific message levels. Cyclin D1 overexpression was associated with a poorly differentiated histology (P = 0.04), less lymphocytic infiltration of the tumour (P = 0.02) and a reduction in local relapse rate (P = 0.01). The relative risk of local relapse was 9.1 in tumours without cyclin D1 overexpression (P = 0.01, Cox regression analysis). We conclude that genetic alteration of cyclin D1 is a key abnormality in lung carcinogenesis and may have diagnostic and prognostic importance in the treatment of resectable NSCLC. Images Figure 1 Figure 2 Figure 3 PMID:8562333

  14. Clear cell carcinomas of the ovary: a multi-institutional study of 129 cases in Korea with prognostic significance of Emi1 and Galectin-3.

    PubMed

    Min, Kyueng-Whan; Park, Moon Hyang; Hong, Sung Ran; Lee, Heejung; Kwon, Sun Young; Hong, Sook Hee; Joo, Hee Jae; Park, In Ae; An, Hee Jung; Suh, Kwang Sun; Oh, Hoon Kyu; Yoo, Chong Woo; Kim, Mi Jin; Chang, Hee Kyung; Jun, Sun Young; Yoon, Hye Kyoung; Chang, Eun Deok; Kim, Dong Won; Kim, Insun

    2013-01-01

    Accurate diagnosis of ovarian clear cell carcinoma (CCC) is important because of its poor prognosis with chemoresistance and a high recurrent rate. The clinicopathologic characteristics and prognostic significance of the cell cycle regulator [early mitotic inhibitor-1 (Emi1)] and galactoside-binding protein (Galectin-3) were evaluated. Among 155 CCCs from 18 hospitals in Korea between 1995 and 2006, 129 pure CCCs were selected with consensus using immunohistochemical stains for hepatocyte nuclear factor-1β, Wilms' tumor protein, and estrogen receptor. The expressions of Emi1, Galectin-3, p53, and Ki-67 labeling index were analyzed with clinicopathologic parameters and the patient's survival. The mean age of the patients was 49.6 yr; the tumors were bilateral in 10.9%, and the average size was 12 cm. Adenofibromatous component was found in 7%, and endometriosis in 48.1% of the cases. Psammoma body was seen in 16.3%. Disease-free survival and overall survival rates were 78.3% and 79.1%, respectively. The International Federation of Obstetrics and Gynecology (FIGO) stage was the most important prognostic indicator. Emi1 expression (>5%) was seen in 23.3% of CCCs, and associated with high FIGO grades and poor overall survival (P<0.05). High Galectin-3 (≥80%) expression was seen in 59.7% of CCCs, and associated with FIGO stages III and IV, and high Ki-67 labeling index. High Ki-67 labeling index (≥50%) and p53 expression (≥50%) were seen in 27.1% and 18.6% of CCCs, respectively, but there was no clinicopathologic and prognostic significance. On the basis of the fact that the expression of Emi1 in CCC was correlated with a high histologic grade and worse overall survival, target therapy using inhibitors of Emi1 may be tried in the management of CCC patients with Emi1 expression. PMID:23202783

  15. The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma.

    PubMed

    Papanikolaou, X; Alapat, D; Rosenthal, A; Stein, C; Epstein, J; Owens, R; Yaccoby, S; Johnson, S; Bailey, C; Heuck, C; Tian, E; Joiner, A; van Rhee, F; Khan, R; Zangari, M; Jethava, Y; Waheed, S; Davies, F; Morgan, G; Barlogie, B

    2015-08-01

    As part of Total Therapy (TT) 3b, baseline marrow aspirates were subjected to two-color flow cytometry of nuclear DNA content and cytoplasmic immunoglobulin (DNA/CIG) as well as plasma cell gene expression profiling (GEP). DNA/CIG-derived parameters, GEP and standard clinical variables were examined for their effects on overall survival (OS) and progression-free survival (PFS). Among DNA/CIG parameters, the percentage of the light chain-restricted (LCR) cells and their cytoplasmic immunoglobulin index (CIg) were linked to poor outcome. In the absence of GEP data, low CIg <2.8, albumin <3.5 g/dl and age ⩾65 years were significantly associated with inferior OS and PFS. When GEP information was included, low CIg survived the model along with GEP70-defined high risk and low albumin. Low CIg was linked to beta-2-microglobulin >5.5 mg/l, a percentage of LCR cells exceeding 50%, C-reactive protein ⩾8 mg/l and GEP-derived high centrosome index. Further analysis revealed an association of low CIg with 12 gene probes implicated in cell cycle regulation, differentiation and drug transportation from which a risk score was developed in TT3b that held prognostic significance also in TT3a, TT2 and HOVON trials, thus validating its general applicability. Low CIg is a powerful new prognostic variable and has identified potentially drug-able targets. PMID:25753926

  16. The flow cytometry-defined light chain cytoplasmic immunoglobulin index and an associated 12-gene expression signature are independent prognostic factors in multiple myeloma

    PubMed Central

    Papanikolaou, X; Alapat, D; Rosenthal, A; Stein, C; Epstein, J; Owens, R; Yaccoby, S; Johnson, S; Bailey, C; Heuck, C; Tian, E; Joiner, A; van Rhee, F; Khan, R; Zangari, M; Jethava, Y; Waheed, S; Davies, F; Morgan, G; Barlogie, B

    2015-01-01

    As part of Total Therapy (TT) 3b, baseline marrow aspirates were subjected to two-color flow cytometry of nuclear DNA content and cytoplasmic immunoglobulin (DNA/CIG) as well as plasma cell gene expression profiling (GEP). DNA/CIG-derived parameters, GEP and standard clinical variables were examined for their effects on overall survival (OS) and progression-free survival (PFS). Among DNA/CIG parameters, the percentage of the light chain-restricted (LCR) cells and their cytoplasmic immunoglobulin index (CIg) were linked to poor outcome. In the absence of GEP data, low CIg <2.8, albumin <3.5 g/dl and age ⩾65 years were significantly associated with inferior OS and PFS. When GEP information was included, low CIg survived the model along with GEP70-defined high risk and low albumin. Low CIg was linked to beta-2-microglobulin >5.5 mg/l, a percentage of LCR cells exceeding 50%, C-reactive protein ⩾8 mg/l and GEP-derived high centrosome index. Further analysis revealed an association of low CIg with 12 gene probes implicated in cell cycle regulation, differentiation and drug transportation from which a risk score was developed in TT3b that held prognostic significance also in TT3a, TT2 and HOVON trials, thus validating its general applicability. Low CIg is a powerful new prognostic variable and has identified potentially drug-able targets. PMID:25753926

  17. Evaluating the prognostic significance of FBXW7 expression level in human breast cancer by a meta-analysis of transcriptional profiles

    PubMed Central

    Wei, Guangwei; Wang, Yunshan; Zhang, Pengju; Lu, Jing; Mao, Jian-Hua

    2012-01-01

    The tumor suppressor gene FBXW7 is mutated in numerous types of human cancers leading to loss of its function and/or expression. However the clinic significance of FBXW7 alterations remains largely unknown. Here, we carried out a meta-analysis of 10 gene expression microarray studies for a total 1900 patients of breast cancer with clinic information to evaluate the prognostic impact of FBXW7 mRNA expression. The FBXW7 mRNA levels significantly reduced in breast cancer compared to normal tissues. In addition, significant difference in the FBXW7 mRNA levels was found among molecular subtypes (normal-like, luminal A, luminal B, ERBB2 and basal). ERBB2 and basal tumors had significantly lower average FBXW7 mRNA level than normal-like tumors, whereas luminal A and B tumors have the lowest average FBXW7 mRNA level. The patients with higher FBXW7 mRNA level significantly increased disease-free survival, particularly in the group of patients with ER negative and basal subtype tumors. Moreover, higher FBXW7 mRNA level also significantly increased overall survival in the patients with ER negative tumors. But we strikingly found opposite effect of FBXW7 expression on overall survival in different subtypes. The patients with higher FBXW7 mRNA level significantly decreased overall survival in normal-like subtype while the patients with higher FBXW7 mRNA level significantly increased overall survival in ERBB2 and Basal subtype. Taken together, our results suggest that FBXW7 mRNA levels were a prognostic factor for disease-free and overall survival according to ER status and molecular subtypes. PMID:23105958

  18. Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact.

    PubMed

    Fornara, O; Bartek, J; Rahbar, A; Odeberg, J; Khan, Z; Peredo, I; Hamerlik, P; Bartek, J; Stragliotto, G; Landázuri, N; Söderberg-Nauclér, C

    2016-02-01

    Glioblastoma (GBM) is associated with poor prognosis despite aggressive surgical resection, chemotherapy, and radiation therapy. Unfortunately, this standard therapy does not target glioma cancer stem cells (GCSCs), a subpopulation of GBM cells that can give rise to recurrent tumors. GBMs express human cytomegalovirus (HCMV) proteins, and previously we found that the level of expression of HCMV immediate-early (IE) protein in GBMs is a prognostic factor for poor patient survival. In this study, we investigated the relation between HCMV infection of GBM cells and the presence of GCSCs. Primary GBMs were characterized by their expression of HCMV-IE and GCSCs marker CD133 and by patient survival. The extent to which HCMV infection of primary GBM cells induced a GCSC phenotype was evaluated in vitro. In primary GBMs, a large fraction of CD133-positive cells expressed HCMV-IE, and higher co-expression of these two proteins predicted poor patient survival. Infection of GBM cells with HCMV led to upregulation of CD133 and other GSCS markers (Notch1, Sox2, Oct4, Nestin). HCMV infection also promoted the growth of GBM cells as neurospheres, a behavior typically displayed by GCSCs, and this phenotype was prevented by either chemical inhibition of the Notch1 pathway or by treatment with the anti-viral drug ganciclovir. GBM cells that maintained expression of HCMV-IE failed to differentiate into neuronal or astrocytic phenotypes. Our findings imply that HCMV infection induces phenotypic plasticity of GBM cells to promote GCSC features and may thereby increase the aggressiveness of this tumor. PMID:26138445

  19. Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy

    PubMed Central

    de Souza, Carolina Rosal Teixeira; Montenegro, Raquel Carvalho; Rey, Juan Antonio; Carvalho, Antônio Alberto; Assumpção, Paulo Pimentel; Khayat, André Salim; Pinto, Giovanny Rebouças; Demachki, Sâmia; de Arruda Cardoso Smith, Marília; Burbano, Rommel Rodríguez

    2013-01-01

    Breast cancer is a complex disease, with heterogeneous clinical evolution. Several analyses have been performed to identify the risk factors for breast cancer progression and the patients who respond best to a specific treatment. We aimed to evaluate whether the hormone receptor expression, HER2 and MYC genes and their protein status, and KRAS codon 12 mutations may be prognostic or predictive biomarkers of breast cancer. Protein, gene and mutation status were concomitantly evaluated in 116 breast tumors from women who underwent neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide. We observed that MYC expression was associated with luminal B and HER2 overexpression phenotypes compared to luminal A (p<0.05). The presence of MYC duplication or polysomy 8, as well as KRAS mutation, were also associated with the HER2 overexpression subtype (p<0.05). MYC expression and MYC gain were more frequently observed in early-onset compared to late-onset tumors (p<0.05). KRAS mutation was a risk factor of grade 3 tumors (p<0.05). A multivariate logistic regression demonstrated that MYC amplification defined as MYC/nucleus ratio of ≥2.5 was a protective factor for chemotherapy resistance. On the other hand, age and grade 2 tumors were a risk factor. Additionally, luminal B, HER2 overexpression, and triple-negative tumors presented increased odds of being resistant to chemotherapy relative to luminal A tumors. Thus, breast tumors with KRAS codon 12 mutations seem to present a worse prognosis. Additionally, MYC amplification may help in the identification of tumors that are sensitive to doxorubicin plus cyclophosphamide treatment. If confirmed in a large set of samples, these markers may be useful for clinical stratification and prognosis. PMID:23555992

  20. A pilot study of the prognostic significance of metabolic tumor size measurements in PET/CT imaging of lymphomas

    NASA Astrophysics Data System (ADS)

    Kallergi, Maria; Botsivali, Maria; Politis, Nikolaos; Menychtas, Dimitrios; Georgakopoulos, Alexandros; Chatziioannou, Sofia

    2015-03-01

    This study explores changes in metabolic tumor volume, metabolic tumor diameter, and maximum standardized uptake value (SUVmax), for earlier and more accurate identification of lymphomas' response to treatment using 18F- FDG PET/CT. Pre- and post-treatment PET/CT studies of 20 patients with Hodgkin disease (HL) and 7 patients with non- Hodgkin lymphoma (NHL) were retrospectively selected for this study. The diameter and volume of the metabolic tumor was determined by an in-house developed adaptive local thresholding technique based on a 50% threshold of the maximum pixel value within a region. Statistical analysis aimed at exploring associations between metabolic size measurements and SUVmax and the ability of the three biomarkers to predict the patients' response to treatment as defined by the four classes in the European Organization for Research and Treatment of Cancer (EORTC) guidelines. Results indicated moderate correlations between % change in metabolic tumor volume and % change in metabolic tumor maximum diameter (R=0.51) and between % change in maximum diameter and % change in SUVmax (R=0.52). The correlation between % change in tumor volume and % change in SUVmax was weak (R=0.24). The % change in metabolic tumor size, either volume or diameter, was a "very strong" predictor of response to treatment (R=0.89), stronger than SUVmax (R=0.63). In conclusion, metabolic tumor volume could have important prognostic value, possibly higher than maximum metabolic diameter or SUVmax that are currently the standard of practice. Volume measurements, however, should be based on robust and standardized segmentation methodologies to avoid variability. In addition, SUV-peak or lean body mass corrected SUV-peak may be a better PET biomarker than SUVmax when SUV-volume combinations are considered.

  1. Prognostic significance of FLT3 internal tandem duplication and NPM1 mutations in acute myeloid leukemia in an unselected patient population.

    PubMed

    Suzuki, Rikio; Onizuka, Makoto; Kojima, Minoru; Shimada, Masako; Okamura, Kaori; Fukagawa, Satomi; Tsuboi, Kosuke; Kikuchi, Ako; Kobayashi, Hiroyuki; Shintani, Ayumi; Ogawa, Yoshiaki; Kawada, Hiroshi; Hotta, Tomomitsu; Ando, Kiyoshi

    2007-12-01

    Mutations in the fms-like tyrosine kinase 3 (FLT3) gene containing an internal tandem duplication (FLT3/ITD) or mutations in the nucleophosmin 1 gene (NPM1) are thought to be prognostic indicators in acute myeloid leukemia (AML). Previous studies suggested that FLT3/ITD mutation indicates a poor prognosis and that NPM1 mutation indicates a more favorable one, but these studies were often performed with selected patient populations. We investigated the clinical significance of these mutations at our institution with an unselected group of patients with newly diagnosed AML. This group included patients > or =60 years old and those with a poor performance status. Using polymerase chain reaction and sequencing analyses, we detected FLT3/ITD mutations in 12 patients (20.0%) and NPM1 mutations in 7 patients (11.7%) among a group of 60 patients. There was a nonsignificant trend for FLT3/ITD mutation to be associated with a poorer predicted overall survival (OS) probability in this population. In contrast, OS was significantly higher in patients with wild-type NPM1 than in patients with NPM1 mutation, both for all AML patients and for AML patients with a normal karyotype. In this general and unselected AML patient population, NPM1 mutation was not a prognostic indicator of a favorable outcome. PMID:18192111

  2. Prognostic significance of infarct core pathology revealed by quantitative non-contrast in comparison with contrast cardiac magnetic resonance imaging in reperfused ST-elevation myocardial infarction survivors

    PubMed Central

    Carrick, David; Haig, Caroline; Rauhalammi, Sam; Ahmed, Nadeem; Mordi, Ify; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Hood, Stuart; Watkins, Stuart; Lindsay, Mitchell; Mahrous, Ahmed; Ford, Ian; Tzemos, Niko; Sattar, Naveed; Welsh, Paul; Radjenovic, Aleksandra; Oldroyd, Keith G.; Berry, Colin

    2016-01-01

    Aims To assess the prognostic significance of infarct core tissue characteristics using cardiac magnetic resonance (CMR) imaging in survivors of acute ST-elevation myocardial infarction (STEMI). Methods and results We performed an observational prospective single centre cohort study in 300 reperfused STEMI patients (mean ± SD age 59 ± 12 years, 74% male) who underwent CMR 2 days and 6 months post-myocardial infarction (n = 267). Native T1 was measured in myocardial regions of interest (n = 288). Adverse remodelling was defined as an increase in left ventricular (LV) end-diastolic volume ≥20% at 6 months. All-cause death or first heart failure hospitalization was a pre-specified outcome that was assessed during follow-up (median duration 845 days). One hundred and sixty (56%) patients had a hypo-intense infarct core disclosed by native T1. In multivariable regression, infarct core native T1 was inversely associated with adverse remodelling [odds ratio (95% confidence interval (CI)] per 10 ms reduction in native T1: 0.91 (0.82, 0.00); P = 0.061). Thirty (10.4%) of 288 patients died or experienced a heart failure event and 13 of these events occurred post-discharge. Native T1 values (ms) within the hypo-intense infarct core (n = 160 STEMI patients) were inversely associated with the risk of all-cause death or first hospitalization for heart failure post-discharge (for a 10 ms increase in native T1: hazard ratio 0.730, 95% CI 0.617, 0.863; P < 0.001) including after adjustment for left ventricular ejection fraction, infarct core T2 and myocardial haemorrhage. The prognostic results for microvascular obstruction were similar. Conclusion Infarct core native T1 represents a novel non-contrast CMR biomarker with potential for infarct characterization and prognostication in STEMI survivors. Confirmatory studies are warranted. ClinicalTrials.gov identifier NCT02072850. PMID:26261290

  3. The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia

    PubMed Central

    Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

    2015-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

  4. The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

    PubMed

    Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

    2015-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

  5. Global histone deacetylase enzymatic activity is an independent prognostic marker associated with a shorter overall survival in chronic lymphocytic leukemia patients

    PubMed Central

    Van Damme, Michaël; Crompot, Emerence; Meuleman, Nathalie; Mineur, Philippe; Dessars, Barbara; El Housni, Hakim; Bron, Dominique; Lagneaux, Laurence; Stamatopoulos, Basile

    2014-01-01

    Histone deacetylases (HDAC) play a crucial role in transcriptional regulation and are often deregulated in many cancers. However, global HDAC enzymatic activity has never been investigated in Chronic Lymphocytic Leukemia (CLL). We measured HDAC activity in protein extracts from CD19+ B-cells purified from 114 CLL patients with a median follow-up of 91 months (range: 11–376). HDAC activity was equivalent in CLL and normal B-cells but higher in patients who died during the study than in living patients (152.1 vs. 65.04 pmol; P = 0.0060). Furthermore, HDAC activity correlated with treatment-free survival (TFS; P = 0.0156) and overall survival (OS; P < 0.0001): patients with low HDAC activity (n = 75) had a median TFS and OS of 101 and >376 months, respectively, whereas patients with high HDAC activity (n = 39) had a median TFS and OS of 47 and 137 months, respectively. Multivariate analyses indicated that HDAC activity is an independent predictor of OS (hazard ratio = 7.68; P = 0.0017). Finally, HDAC activity increased after B-cell receptor stimulation using IgM, suggesting a role for microenvironment stimuli (n = 10; P = 0.0371). In conclusion, high HDAC activity in CLL B-cells is associated with shorter TFS and OS and is an independent marker of OS, refining the use of other prognostic factors. This work provides a biological base for the use of HDAC inhibitors in CLL treatment. PMID:25437053

  6. Prognostic Significance of Central Pulse Pressure for Mortality in Patients With Coronary Artery Disease Receiving Repeated Percutaneous Coronary Intervention

    PubMed Central

    Lin, Mao-Jen; Chen, Chun-Yu; Lin, Hau-De; Lin, Chung-Sheng; Wu, Han-Ping

    2016-01-01

    were predictors for repeated PCI. Most importantly, CPP was strongly associated with MI attack, CV mortality, and all-cause mortality, and could serve as a prognostic parameter for mortality in patients with CAD after performing repeated PCI. PMID:27043689

  7. Prognostic Significance of Central Pulse Pressure for Mortality in Patients With Coronary Artery Disease Receiving Repeated Percutaneous Coronary Intervention.

    PubMed

    Lin, Mao-Jen; Chen, Chun-Yu; Lin, Hau-De; Lin, Chung-Sheng; Wu, Han-Ping

    2016-03-01

    for repeated PCI. Most importantly, CPP was strongly associated with MI attack, CV mortality, and all-cause mortality, and could serve as a prognostic parameter for mortality in patients with CAD after performing repeated PCI. PMID:27043689

  8. [Prognostic significance of cytogenetic changes in patients with acute myeloid leukemia (AML). (Analysis of results in 105 patients treated at the Hemato-oncology Clinic of the University Hospital in Olomouc from 1997 to 2000].

    PubMed

    Jarosová, M; Indrák, K; Holzerová, M; Hubácek, J; Faber, E; Papajík, T; Raida, L; Szotkowski, T; Knotková, R; Hlusí, T; Jedlicková, K; Pikalová, Z; Sulovská, I

    2001-09-01

    = 0.34), but fit appeared in evaluation of both groups in patients under 55 years. It seems that in patients in age 55 and more the age is independent poor prognostic factor and findings of chromosomal aberrations do not significantly influence prognosis. PMID:11693065

  9. Prognostic Significance of NPM1 Mutations in the Absence of FLT3–Internal Tandem Duplication in Older Patients With Acute Myeloid Leukemia: A SWOG and UK National Cancer Research Institute/Medical Research Council Report

    PubMed Central

    Ostronoff, Fabiana; Othus, Megan; Lazenby, Michelle; Estey, Elihu; Appelbaum, Frederick R.; Evans, Anna; Godwin, John; Gilkes, Amanda; Kopecky, Kenneth J.; Burnett, Alan; List, Alan F.; Fang, Min; Oehler, Vivian G.; Petersdorf, Stephen H.; Pogosova-Agadjanyan, Era L.; Radich, Jerald P.; Willman, Cheryl L.; Meshinchi, Soheil; Stirewalt, Derek L.

    2015-01-01

    Purpose Younger patients with acute myeloid leukemia (AML) harboring NPM1 mutations without FLT3–internal tandem duplications (ITDs; NPM1-positive/FLT3-ITD–negative genotype) are classified as better risk; however, it remains uncertain whether this favorable classification can be applied to older patients with AML with this genotype. Therefore, we examined the impact of age on the prognostic significance of NPM1-positive/FLT3-ITD–negative status in older patients with AML. Patients and Methods Patients with AML age ≥ 55 years treated with intensive chemotherapy as part of Southwest Oncology Gorup (SWOG) and UK National Cancer Research Institute/Medical Research Council (NCRI/MRC) trials were evaluated. A comprehensive analysis first examined 156 patients treated in SWOG trials. Validation analyses then examined 1,258 patients treated in MRC/NCRI trials. Univariable and multivariable analyses were used to determine the impact of age on the prognostic significance of NPM1 mutations, FLT3-ITDs, and the NPM1-positive/FLT3-ITD–negative genotype. Results Patients with AML age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype treated in SWOG trials had a significantly improved 2-year overall survival (OS) as compared with those without this genotype (70% v 32%; P < .001). Moreover, patients age 55 to 65 years with NPM1-positive/FLT3-ITD–negative genotype had a significantly improved 2-year OS as compared with those age > 65 years with this genotype (70% v 27%; P < .001); any potential survival benefit of this genotype in patients age > 65 years was marginal (27% v 16%; P = .33). In multivariable analysis, NPM1-positive/FLT3-ITD–negative genotype remained independently associated with an improved OS in patients age 55 to 65 years (P = .002) but not in those age > 65 years (P = .82). These results were confirmed in validation analyses examining the NCRI/MRC patients. Conclusion NPM1-positive/FLT3-ITD–negative genotype remains a relatively

  10. Focal versus diffuse anaplasia in Wilms tumor--new definitions with prognostic significance: a report from the National Wilms Tumor Study Group.

    PubMed

    Faria, P; Beckwith, J B; Mishra, K; Zuppan, C; Weeks, D A; Breslow, N; Green, D M

    1996-08-01

    Anaplasia, defined by the presence of extreme nuclear and mitotic atypia, is a potent marker of adverse prognosis in Wilms tumor (WT). Anaplastic WT cells apparently have increased resistance to therapy rather than increased aggressiveness. The distribution of anaplasia should therefore have critical prognostic relevance. The original definitions for focal anaplasia (FA) and diffuse anaplasia (DA) were based on quantitative rather than topographical criteria and lacked prognostic significance. A new definition was developed based on the distribution of anaplastic changes within the tumor: FA applies only to tumors with anaplasia confined to one or a few discrete loci within the primary tumor, with no anaplasia or marked nuclear atypia elsewhere. This revised definition was evaluated in 165 cases with anaplastic WT entered on the third and fourth National Wilms Tumor Study. Only three relapses and one death occurred among 39 cases with FA, regardless of tumor stage, a result comparable to that for nonanaplastic WT. Eight children with metastases at diagnosis and FA in the primary tumor were alive and free of relapse; 22 of 23 children with stage IV DA WT died of tumor. This new definition reinforces the importance of carefully documenting the exact site from which each tumor section is obtained. PMID:8712292

  11. p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function.

    PubMed

    Xu-Monette, Zijun Y; Zhang, Shanxiang; Li, Xin; Manyam, Ganiraju C; Wang, Xiao-Xiao; Xia, Yi; Visco, Carlo; Tzankov, Alexandar; Zhang, Li; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L; Hsi, Eric D; Choi, William W L; van Krieken, J Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J M; Zhao, Xiaoying; Møller, Michael B; Parsons, Ben M; Winter, Jane N; Piris, Miguel A; Medeiros, L Jeffrey; Young, Ken H

    2016-02-01

    The role of p53 family member p63 in oncogenesis is the subject of controversy. Limited research has been done on the clinical implications of p63 expression in diffuse large B-cell lymphoma (DLBCL). In this study, we assessed p63 expression in de novo DLBCL samples (n=795) by immunohistochemistry with a pan-p63-monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes. p63 expression was observed in 42.5% of DLBCL, did not correlate with p53 levels, but correlated with p21, MDM2, p16INK4A, Ki-67, Bcl-6, IRF4/MUM-1 and CD30 expression, REL gains, and BCL6 translocation. p63 was an independent favorable prognostic factor in DLBCL, which was most significant in patients with International Prognostic Index (IPI) >2, and in activated-B-cell-like DLBCL patients with wide- type TP53. The prognostic impact in germinal-center-B-cell-like DLBCL was not apparent, which was likely due to the association of p63 expression with high-risk IPI, and potential presence of ∆Np63 isoform in TP63 rearranged patients (a mere speculation). Gene expression profiling suggested that p63 has both overlapping and distinct functions compared with p53, and that p63 and mutated p53 antagonize each other. In summary, p63 has p53-like and p53-independent functions and favorable prognostic impact, however this protective effect can be abolished by TP53 mutations. PMID:26878872

  12. p63 expression confers significantly better survival outcomes in high-risk diffuse large B-cell lymphoma and demonstrates p53-like and p53-independent tumor suppressor function

    PubMed Central

    Manyam, Ganiraju C.; Wang, Xiao-xiao; Xia, Yi; Visco, Carlo; Tzankov, Alexandar; Zhang, Li; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Zhao, Xiaoying; Møller, Michael B.; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Medeiros, L. Jeffrey; Young, Ken H.

    2016-01-01

    The role of p53 family member, p63 in oncogenesis is the subject of controversy. Limited research has been done on the clinical implications of p63 expression in diffuse large B-cell lymphoma (DLBCL). In this study, we assessed p63 expression in de novo DLBCL samples (n=795) by immunohistochemistry with a pan-p63-monoclonal antibody and correlated it with other clinicopathologic factors and clinical outcomes. p63 expression was observed in 42.5% of DLBCL, did not correlate with p53 levels, but correlated with p21, MDM2, p16INK4A, Ki-67, Bcl-6, IRF4/MUM-1 and CD30 expression, REL gains, and BCL6 translocation. p63 was an independent favorable prognostic factor in DLBCL, which was most significant in patients with International Prognostic Index (IPI) >2, and in activated-B-cell–like DLBCL patients with wide-type TP53. The prognostic impact in germinal-center-B-cell–like DLBCL was not apparent, which was likely due to the association of p63 expression with high-risk IPI, and potential presence of ∆Np63 isoform in TP63 rearranged patients (a mere speculation). Gene expression profiling suggested that p63 has both overlapping and distinct functions compared with p53, and that p63 and mutated p53 antagonize each other. In summary, p63 has p53-like and p53-independent functions and favorable prognostic impact, however this protective effect can be abolished by TP53 mutations. PMID:26878872

  13. Prognostic significance of clinical parameters and biological markers in patients with squamous cell carcinoma of the head and neck treated with concurrent chemoradiotherapy.

    PubMed

    Homma, A; Furuta, Y; Oridate, N; Nakano, Y; Kohashi, G; Yagi, K; Nagahashi, T; Yagi, K; Nagahashi, T; Fukuda, S; Inoue, K; Inuyama, Y

    1999-04-01

    Concurrent chemoradiotherapy is reported to have a fair clinical outcome with organ preservation for patients with squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to determine whether biological markers are related to proliferative activity or apoptosis of tumor cells and whether clinical factors are associated with a clinical outcome in SCCHN patients treated with concurrent chemoradiotherapy. Immunostaining with antibodies specific for p53, bcl-2, bax, and MIB-1 was performed to evaluate expression of these proteins in formalin-fixed, paraffin-embedded specimens of 111 SCCHN patients treated with concurrent chemoradiotherapy (carboplatin, 100 mg/m2, four to six times every week; total radiation therapy dose of 40-65 Gy over 4-6.5 weeks). Multivariate analysis indicated that nodal status was a significant indicator of overall survival (OS; P = 0.001) and locoregional control (LRC; P = 0.002). In a univariate analysis, patients with a low MIB-1-positive index (< 40%) had better OS than those with a high MIB-1-positive index (> or = 40%; P = 0.013), although the difference was not statistically significant in a multivariate analysis (P = 0.060). Patients with bcl-2-positive tumors had better LRC than those with bcl-2-negative tumors, based on a multivariate analysis (P = 0.017). No statistically significant association was found between p53 or bax expression and clinical outcome. These results indicate that nodal status is the major prognostic factor in SCCHN patients treated with concurrent chemoradiotherapy. In addition, our findings suggest that bcl-2 positivity is associated with better LRC and that the proliferative activity of tumor cells might be prognostic for OS. PMID:10213215

  14. Prognostic Significance of the European LeukemiaNet Standardized System for Reporting Cytogenetic and Molecular Alterations in Adults With Acute Myeloid Leukemia

    PubMed Central

    Mrózek, Krzysztof; Marcucci, Guido; Nicolet, Deedra; Maharry, Kati S.; Becker, Heiko; Whitman, Susan P.; Metzeler, Klaus H.; Schwind, Sebastian; Wu, Yue-Zhong; Kohlschmidt, Jessica; Pettenati, Mark J.; Heerema, Nyla A.; Block, AnneMarie W.; Patil, Shivanand R.; Baer, Maria R.; Kolitz, Jonathan E.; Moore, Joseph O.; Carroll, Andrew J.; Stone, Richard M.; Larson, Richard A.; Bloomfield, Clara D.

    2012-01-01

    Purpose To evaluate the prognostic significance of the international European LeukemiaNet (ELN) guidelines for reporting genetic alterations in acute myeloid leukemia (AML). Patients and Methods We analyzed 1,550 adults with primary AML, treated on Cancer and Leukemia Group B first-line trials, who had pretreatment cytogenetics and, for cytogenetically normal patients, mutational status of NPM1, CEBPA, a