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Sample records for independently significant prognostic

  1. Significance Analysis of Prognostic Signatures

    PubMed Central

    Beck, Andrew H.; Knoblauch, Nicholas W.; Hefti, Marco M.; Kaplan, Jennifer; Schnitt, Stuart J.; Culhane, Aedin C.; Schroeder, Markus S.; Risch, Thomas; Quackenbush, John; Haibe-Kains, Benjamin

    2013-01-01

    A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that “random” gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated

  2. The prognostic significance of steroid receptor co-regulators in breast cancer: co-repressor NCOR2/SMRT is an independent indicator of poor outcome.

    PubMed

    Green, Andrew R; Burney, Claire; Granger, Christopher J; Paish, E Claire; El-Sheikh, Somaia; Rakha, Emad A; Powe, Desmond G; Macmillan, R Douglas; Ellis, Ian O; Stylianou, Eleni

    2008-08-01

    Advances in understanding the molecular basis of breast cancer has necessitated a definition of improved indicators of prognosis that are central to the underlying cancer biology and that reflect the heterogeneous nature of the disease. This study investigates the pattern of expression of the steroid receptor co-regulators NCOA1/SRC1, NCOA3/RAC3, NCOR2/SMRT, and CBP/p300 in breast cancer. The aims were to identify whether their expression was related to patient outcome, their relationships to known prognostic factors and to provide a basis for further research into the mechanistic significance of such associations. The protein levels of steroid receptor co-regulators were assessed by immunohistochemistry in a large well-characterised series of breast carcinomas prepared as tissue microarrays. Relationships between these targets, other clinicopathological variables and patients' outcome were examined. NCOR2/SMRT was an independent prognostic indicator of overall patient survival (OS) and disease free interval (DFI) and was significantly correlated with distant metastases and local recurrence whereas tumours expressing NCOA1/SRC1 had a significantly longer OS and DFI. There were also significant correlations between co-regulator expression of NCOA1/SRC1, CBP/p300 and NCOA3/RAC3, which were associated with lower tumour grade. NCOA1/SRC1 was also correlated with smaller tumour size. Furthermore, the co-activators had a significant association with steroid receptors, particularly ERalpha. NCOR2/SMRT is associated with poor patient outcome, independent of other prognostic factors. In contrast, steroid receptor co-activator expression is generally associated with a good prognosis. Further investigations are needed to establish the mechanisms of these links between the steroid receptor co-regulator system and patient outcome.

  3. Identification of the resection severity index as a significant independent prognostic factor for early mortality and observed survival >5 and >10 years after liver resection for hepatocellular carcinoma.

    PubMed

    Gwiasda, Jill; Schulte, Aron; Kaltenborn, Alexander; Ramackers, Wolf; Kleine, Moritz; Beetz, Oliver; Klempnauer, Jürgen; Emmanouilidis, Nikos; Schrem, Harald

    2017-06-01

    This study evaluates predictive factors for observed long-term survival of more than 5 and 10 years for patients after liver resection for hepatocellular carcinoma and compares their life expectancy to the normal national population matched for sex, year of birth and age at resection. 230 patients after primary liver resection for HCC (01.01.1995-31.12.2004) were analyzed. Multivariable logistic regression models were determined based on Cox regression results and their prognostic capability evaluated with areas under the receiver operating characteristic curve (AUROCs). Life years after surgery in deceased patients compared to the normal national population matched for sex, year of birth and age at resection was reduced by median 21.7 years. Independent predictive factors for 10-year survival were age at resection (p < 0.001; OR = 0.898; 95%-CI: 0.846-0.954), UICC 7 tumor staging (p = 0.003; OR = 0.344; 95%-CI: 0.126-0.941) and ASAT (GOT) in U/l divided by Quick in percent multiplied by the extent of liver resection graded in points labelled as the resection severity index (p < 0.001; OR = 0.136; 95%-CI: 0.022-0.843) enabling prediction of 10-year survival with an AUROC of 0.884. The same factors plus revision surgery (yes/no) predict 5-year survival (AUROC 0.736). Liver resection enables predictable long-term survival >5 and > 10 years. The proposed resection severity index quantifies the prognostic relevance of liver cellular damage, synthesis and loss of parenchyma for long-term survival. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Prognostic Significance of Erythropoietin in Pancreatic Adenocarcinoma

    PubMed Central

    Becker, Verena; Giese, Thomas; Bergmann, Frank; Hinz, Ulf; Keleg, Shereen; Heller, Anette; Sipos, Bence; Klingmüller, Ursula; Büchler, Markus W.; Werner, Jens; Giese, Nathalia A.

    2011-01-01

    Background Erythropoietin (Epo) administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC). Methodology The clinico-pathological relevance of hemoglobin (Hb, n = 150), serum Epo (sEpo, n = 87) and tissue expression of Epo/Epo receptor (EpoR, n = 104) was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. Results Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05) and PDAC (p<0.001), reaching anemic grade in one third of patients. While inversely correlating to Hb (r = −0.46), 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99) but not in PDAC (O/P = 0.85). Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01)—although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥16 mU/ml) were not significantly different in M0 (20%) and M1 (30%) groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05). The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. Conclusion/Significance Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how

  5. Prognostic significance of erythropoietin in pancreatic adenocarcinoma.

    PubMed

    Welsch, Thilo; Zschäbitz, Stefanie; Becker, Verena; Giese, Thomas; Bergmann, Frank; Hinz, Ulf; Keleg, Shereen; Heller, Anette; Sipos, Bence; Klingmüller, Ursula; Büchler, Markus W; Werner, Jens; Giese, Nathalia A

    2011-01-01

    Erythropoietin (Epo) administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC). The clinico-pathological relevance of hemoglobin (Hb, n = 150), serum Epo (sEpo, n = 87) and tissue expression of Epo/Epo receptor (EpoR, n = 104) was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05) and PDAC (p<0.001), reaching anemic grade in one third of patients. While inversely correlating to Hb (r = -0.46), 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99) but not in PDAC (O/P = 0.85). Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01)--although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥ 16 mU/ml) were not significantly different in M0 (20%) and M1 (30%) groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05). The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold ≥16 mU/ml by endogenous or exogenous means may predispose to or

  6. An independent evaluation of the potential clinical usefulness of proposed CA-125 indices previously shown to be of prognostic significance in epithelial ovarian cancer.

    PubMed Central

    Cruickshank, D. J.; Paul, J.; Lewis, C. R.; McAllister, E. J.; Kaye, S. B.

    1992-01-01

    CA-125 levels were assessed prior to each of the first three cycles of chemotherapy, in 81 patients with epithelial ovarian cancer receiving first-line chemotherapy. All patients have at least 1 year's follow-up. Thirty-nine patients (48%) have progressed clinically or have died within 1 year of treatment (treatment 'failures'). Three CA-125 indices previously shown to be of prognostic value are assessed for their ability to pick-out these 'failures'. When the indices examined are modified to obtain a specificity for picking out failures just exceeding 90%, the maximum sensitivity obtained was 46%. The use of CA-125 for clinical decision making in ovarian cancer requires further investigation to determine and validate a prognostic index with acceptable sensitivity and specificity, and to determine the clinical impact of treatment decisions made using such an index. PMID:1562469

  7. Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13.

    PubMed

    Gabitass, Rachel F; Annels, Nicola E; Stocken, Deborah D; Pandha, Hardev A; Middleton, Gary W

    2011-10-01

    We undertook a comprehensive analysis of circulating myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) in pancreatic, esophageal and gastric cancer patients and investigated whether MDSCs are an independent prognostic factor for survival. We evaluated a series of plasma cytokines and in particular re-evaluated the Th2 cytokine interleukin-13 (IL-13). Peripheral blood was collected from 131 cancer patients (46 pancreatic, 60 esophageal and 25 gastric) and 54 healthy controls. PBMC were harvested with subsequent flow cytometric analysis of MDSC (HLADR(-) Lin1(low/-) CD33(+) CD11b(+)) and Treg (CD4(+) CD25(+) CD127(low/-) FoxP3(+)) percentages. Plasma IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 (p70), IL-13, IL-17, G-CSF, IFN-γ, TNF-α and VEGF levels were analyzed by the Bio-Plex cytokine assay. Plasma arginase I levels were analyzed by ELISA. MDSCs and Tregs were statistically significantly elevated in pancreatic, esophageal and gastric cancer compared with controls, and MDSC numbers correlated with Treg levels. Increasing MDSC percentage was associated with increased risk of death, and in a multivariate analysis, MDSC level was an independent prognostic factor for survival. A unit increase in MDSC percentage was associated with a 22% increased risk of death (hazard ratio 1.22, 95% confidence interval 1.06-1.41). Arginase I levels were also statistically significantly elevated in upper gastrointestinal cancer patients compared with controls. There was Th2 skewing for cytokine production in all three diseases, and importantly there were significant elevations of the pivotal Th2 cytokine interleukin-13, an increase that correlated with MDSC levels.

  8. Prognostic nutritional index is an independent prognostic factor for gastric cancer patients with peritoneal dissemination

    PubMed Central

    Nie, Runcong; Yuan, Shuqiang; Chen, Shi; Chen, Xiaojiang; Chen, Yongming; Zhu, Baoyan; Qiu, Haibo; Zhou, Zhiwei; Peng, Junsheng; Chen, Yingbo

    2016-01-01

    Objective The predictive and prognostic role of prognostic nutritional index (PNI) in gastric cancer patients with peritoneal dissemination remains unclear. This study aims to explore the role of the PNI in predicting outcomes of gastric cancer patients with peritoneal dissemination. Methods A total of 660 patients diagnosed with gastric adenocarcinoma with peritoneal metastasis between January 2000 and April 2014 at Sun Yat-sen University Cancer Center and the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. The clinicopathologic characteristics and clinical outcomes of patients with peritoneal dissemination were analyzed. Results Compared with PNI-high group, PNI-low group was correlated with advanced age (P=0.036), worse performance status (P<0.001), higher frequency of ascites (P<0.001) and higher frequency of multisite distant metastasis (P<0.001). Kaplan-Meier survival curves showed that PNI-high group had a significantly longer median overall survival than PNI-low group (13.13 vs. 9.03 months, P<0.001). Multivariate survival analysis revealed that Borrmann type IV (P=0.014), presence of ascites (P=0.017) and lower PNI (P=0.041) were independent poor prognostic factors, and palliative surgery (P<0.001) and first-line chemotherapy (P<0.001) were good prognostic factors. For patients receiving palliative surgery, the postoperative morbidity rates in the PNI-low group and PNI-high group were 9.1% and 9.9%, respectively (P=0.797). The postoperative mortality rate was not significantly different between PNI-low and PNI-high groups (2.3% vs. 0.9%, P=0.362). Conclusions PNI is a useful and practical tool for evaluating the nutritional status of gastric cancer patients with peritoneal dissemination, and is an independent prognostic factor for these patients. PMID:28174485

  9. Physiologic and prognostic significance of "alpha coma".

    PubMed Central

    Iragui, V J; McCutchen, C B

    1983-01-01

    A patient with posthypoxic "alpha coma" is described whose EEGs were recorded before coma, within two hours following the onset of coma and after recovery. The differences observed between the alpha activity during coma and that seen before and after suggest that the alpha activity during coma and the physiologic alpha rhythm are different phenomena. This case, as well as others reported, also suggests that "alpha coma" resolving in the first 24 hours following hypoxia may have a better prognosis than "alpha coma" detected after the first day, and stresses the need for EEG monitoring begun in the immediate period following hypoxia in order to assess accurately the prognostic significance of this EEG pattern in the early stages of postanoxic encephalopathy. The aetiology of "alpha coma" also affects outcome. The survival rate appears higher in patients with respiratory arrest than in those with combined cardiopulmonary arrest. PMID:6886700

  10. 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.

  11. Prognostic significance of Tiam1 expression in papillary thyroid carcinoma.

    PubMed

    Hsueh, Chuen; Lin, Jen-Der; Yang, Chia-Fen; Chang, Yu-Sun; Chao, Tzu-Chieh; Sun, Jui-Hung; Wu, I-Chin; Tseng, Ngan-Ming; Ueng, Shir-Hwa

    2011-12-01

    T lymphoma and metastasis gene 1 (Tiam1) is a guanine nucleotide exchange factor (GNEF) that regulates the guanosine triphosphatase to facilitate the exchange of guanosine diphosphate for guanosine triphosphate. It specifically activates Rac1, a member of the Rho family of GTPases. Tiam1 is involved in cell proliferation, cytoskeletal organization, cellular adhesion, and transcriptional activation. It has been suggested that alterations in Tiam1 expression might contribute to the progression of various human cancers. The usefulness of Tiam1 expression as a prognostic marker in papillary thyroid carcinoma (PTC) has not been investigated yet. The aim of this study was to analyze the expression of Tiam1 in PTC as well as its association with the clinicopathologic features and prognostic significance. Surgical tissue samples were taken from 106 PTC patients who had been followed up for at least 9.3 years. Strong expression of Tiam1 was detected in 54% of the cases. Tiam1 expression was associated significantly with various clinicopathologic parameters, such as gender (P=0.039), tumor multicentricity (P=0.0124), histologic subtype (P=0.0427), TNM stage (P=0.0151), and distant metastases at diagnosis (P=0.0001). Survival analysis showed that the Tiam1 low-expression group had a significantly shorter overall survival time than Tiam1 high-expression group (P=0.0007). Multivariate analysis showed that Tiam1 expression was a significant and independent prognostic indicator (P=0.0090) for PTC patients. Tiam1 expression may be a novel and independent prognostic marker of PTC patients. © Springer-Verlag 2011

  12. Infarct volume after glioblastoma surgery as an independent prognostic factor

    PubMed Central

    Bette, Stefanie; Wiestler, Benedikt; Kaesmacher, Johannes; Huber, Thomas; Gerhardt, Julia; Barz, Melanie; Delbridge, Claire; Ryang, Yu-Mi; Ringel, Florian; Zimmer, Claus; Meyer, Bernhard; Boeckh-Behrens, Tobias; Kirschke, Jan S.; Gempt, Jens

    2016-01-01

    Postoperative ischemia is associated with reduced functional independence measured by karnofsky performance score (KPS), which correlates well with overall survival. Other studies suggest that postoperative hypoxia might initiate infiltrative tumor growth. Therefore, aim of this study was to analyze the impact of infarct volume on overall survival and progression free survival (PFS) of glioblastoma patients. 251 patients with surgery for a newly diagnosed glioblastoma (WHO IV) were retrospectively assessed. Pre- and postoperative KPS, date of death/last follow-up and histopathological markers were recorded. Pre- and postoperative tumor volume and the volume of postoperative infarction were manually segmented. A significant correlation of infarct volume with postoperative KPS decrease (P = 0.001) was observed. Infarct volume showed a significant impact on overall survival (P = 0.014), but not on PFS (P = 0.112) in univariate analysis. This effect increased in the subgroup of patients with near-total tumor resection (> 90%) (overall survival: P = 0.006, PFS: P = 0.066). Infarct volume remained as an independent prognostic factor for overall survival in multivariate analysis (HR 1.013 [1.000–1.026], P = 0.042) including other prognostic factors (age, extent of resection, postoperative KPS). Postoperative infarct volume significantly correlates as an independent factor with overall survival after glioblastoma surgery. Besides the influence of perioperative infarction on postoperative KPS, postoperative hypoxia might also have an effect on tumor biology initiating infiltrative growth and therefore impaired survival. PMID:27566556

  13. Expression and prognostic significance of lysozyme in male breast cancer.

    PubMed

    Serra, Carlos; Vizoso, Francisco; Alonso, Lorena; Rodríguez, Juan C; González, Luis O; Fernández, María; Lamelas, María L; Sánchez, Luis M; García-Muñiz, José L; Baltasar, Aniceto; Medrano, Justo

    2002-01-01

    Lysozyme, one of the major protein components of human milk that is also synthesized by a significant percentage of breast carcinomas, is associated with lesions that have a favorable outcome in female breast cancer. Here we evaluate the expression and prognostic value of lysozyme in male breast cancer (MBC). Lysozyme expression was examined by immunohistochemical methods in a series of 60 MBC tissue sections and in 15 patients with gynecomastia. Staining was quantified using the HSCORE (histological score) system, which considers both the intensity and the percentage of cells staining at each intensity. Prognostic value of lysozyme was retrospectively evaluated by multivariate analysis taking into account conventional prognostic factors. Lysozyme immunostaining was negative in all cases of gynecomastia. A total of 27 of 60 MBC sections (45%) stained positively for this protein, but there were clear differences among them with regard to the intensity and percentage of stained cells. Statistical analysis showed that lysozyme HSCORE values in relation to age, tumor size, nodal status, histological grade, estrogen receptor status, metastasis and histological type did not increase the statistical significance. Univariate analysis confirmed that both nodal involvement and lysozyme values were significant predictors of short-term relapse-free survival. Multivariate analysis, according to Cox's regression model, also showed that nodal status and lysozyme levels were significant independent indicators of short-term relapse-free survival. Tumor expression of lysozyme is associated with lesions that have an unfavorable outcome in male breast cancer. This milk protein may be a new prognostic factor in patients with breast cancer.

  14. Geminin expression in small lung adenocarcinomas: implication of prognostic significance.

    PubMed

    Haruki, Tomohiro; Shomori, Kohei; Hamamoto, Yuki; Taniguchi, Yuji; Nakamura, Hiroshige; Ito, Hisao

    2011-03-01

    Geminin is an important molecule which plays a role in cell cycle regulation, and this has been considered to be a useful biomarker of cell proliferation. The purpose of this study was to evaluate the pathological and prognostic significance of geminin expression in small lung adenocarcinoma (AC). We performed Western blot analysis of five human lung AC cell lines and immunohistochemistry on 100 surgically resected specimens of lung AC with a diameter less than 3 cm. We counted the number of positively stained tumor cells, and calculated the labeling indices (LIs). Geminin proteins were variably detected in all five cell lines examined on Western blotting. The mean LIs for geminin, Ki-67, and MCM7 were 7.5%, 12.3%, and 18.5%, respectively. The geminin LIs were associated with some clinicopathological profiles including gender, histological grade, subtypes, N-status, p-factor, and tumor stage. A significantly worse prognosis was noted in the higher geminin LIs group than in the lower group (p < 0.01). Multivariate Cox regression analysis also confirmed that geminin LIs was an independent prognostic marker in stage IA lung AC patients. These results suggest that geminin is overexpressed in small lung ACs, and geminin LIs might be a useful prognostic indicator in patients with lung AC.

  15. 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

  16. 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

  17. Independent prognostic value of peritoneal immunocytodiagnosis in endometrial carcinoma.

    PubMed

    Benevolo, M; Mariani, L; Vocaturo, G; Vasselli, S; Natali, P G; Mottolese, M

    2000-02-01

    Among the clinical parameters that play a pivotal role in predicting the outcome of patients with endometrial carcinoma, intraperitoneal microscopic dissemination represents an important cause of recurrences. To date, peritoneal cytology has been incorporated into the current surgical staging system (International Federation of Gynecology and Obstetrics 88), although its predictive value remains a controversial issue. In this study the authors investigated the possibility of applying immunocytochemistry (ICC) to the diagnosis of peritoneal washing (PW) aimed at improving conventional cytology and verifying the prognostic value of peritoneal malignant cells. The authors analyzed 182 PWs sampled from endometrial cancer patients. The ICC analysis was performed using two monoclonal antibodies (MAbs)--AR-3 and B72.3--that in combination recognize more than 95% of endometrial carcinomas. The presence of peritoneal-free cancer cells was identified morphologically in 27 of 182 lavages (14.8%) and ICC in 50 of 182 (27.5%), with a significant improvement (p <0.0001). Five-year survival analysis, comparing results of ICC and cytodiagnosis, demonstrated a significant decrease of disease-free survival in patients with peritoneal microscopic disease. Furthermore, multivariate analysis showed that ICC diagnosis of PWs is an independent prognostic factor. Data indicate that the use of selected MAbs allows one to identify cytologically false-negative cases, providing results that are highly predictive of a worse clinical outcome.

  18. [Significance of prognostic parameters in acute pancreatitis].

    PubMed

    Guastella, T; Scuderi, M; Di Stefano, A; Scala, R; Rapisarda, D; Succi, L; Russello, D

    1993-07-01

    The diagnostic and therapeutic approach to Acute Pancreatitis (A.P.) is directly related to the clinical presentation. The Authors reviewed the data of 66 patients, hospitalized between October 1989 and December 1991, to verify the effectiveness of the prognostic criteria suggested by Ranson (1974), Mercadier (1977) and Imrie (1978). A.P. was of biliary origin in the majority of the patients (63.5%); five patients (7.5%) had an acute alcoholic pancreatitis, while the aetiology was traumatic or unknown in the remaining cases. A complicated clinical course was defined by the development of pseudocyst, pancreatic abscess, digestive haemorrhage, death or prolonged hospitalization (more than 20 days). The 28.8% of the patients developed complications during hospitalization. There were seven pancreatic pseudocysts, six pulmonary complications, three renal insufficiencies, two vascular complications, two sepsies and a gastrointestinal haemorrhage. The mean hospitalization period was 15.1 days (range 1-112). The Authors conclude that the three different prognostic criteria are equally useful to test the severity of A.P. attacks allowing to identify patients with the higher risk to develop complications during hospitalization.

  19. Symptoms at diagnosis as independent prognostic factors in retroperitoneal liposarcoma.

    PubMed

    Taguchi, Satoru; Kume, Haruki; Fukuhara, Hiroshi; Morikawa, Teppei; Kakutani, Shigenori; Takeshima, Yuta; Miyazaki, Hideyo; Suzuki, Motofumi; Fujimura, Tetsuya; Nakagawa, Tohru; Ishikawa, Akira; Igawa, Yasuhiko; Homma, Yukio

    2016-02-01

    The prognostic factors of retroperitoneal liposarcoma have yet to be clearly determined due to its rarity, whereas the prognostic value of symptoms at diagnosis has never been evaluated to date. In this context, we reviewed 24 consecutive patients with primary retroperitoneal liposarcoma who underwent surgical resection with curative intent at our institution. The Kaplan-Meier analysis and the log-rank test were used to estimate progression-free survival (PFS; primary endpoint) and sarcoma-specific survival (SSS; secondary endpoint). The effect of various clinicopathological factors, including symptoms at diagnosis, on these two endpoints was assessed with a Cox proportional hazards model. During the study period, 11 patients (45.8%) developed recurrence after the initial surgery and 8 (33.3%) succumbed to retroperitoneal liposarcoma, with a median follow-up of 64 months. A total of 16 patients (66.7%) had symptoms at diagnosis, while the remaining 8 (33.3%) were diagnosed incidentally. The symptoms were palpability of the tumor (n=8); abdominal pain/fullness (n=3); flank pain/fullness (n=2); lower extremity pain (n=1); testicular pain due to varicocele (n=1); and discomfort on urination (n=1). Patients with symptoms at diagnosis were significantly more likely to develop recurrence (log-rank test, P=0.0196) and were also more likely to succumb to sarcoma (P=0.0778) compared with asymptomatic patients. On the multivariate analysis, symptoms at diagnosis and dedifferentiated components were independent predictors of poor PFS, while positive surgical margins were predictors of poor SSS. Given that symptoms at diagnosis are easily accessible for physicians, they may prove to be useful additional prognostic factors for primary retroperitoneal liposarcoma.

  20. The biological and prognostic significance of angiotropism in uveal melanoma.

    PubMed

    Barnhill, Raymond L; Ye, Mengliang; Batistella, Aude; Stern, Marc-Henri; Roman-Roman, Sergio; Dendale, Rémi; Lantz, Olivier; Piperno-Neumann, Sophie; Desjardins, Laurence; Cassoux, Nathalie; Lugassy, Claire

    2017-02-27

    Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and a prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy. Clinical, histopathological, and molecular variables included patient age, gender, extraocular extension, tumor location (ciliary body or not), optic nerve invasion, angiotropism, neurotropism, melanoma cell type, BAP1 mutation, and monosomy 3. Angiotropism was defined as melanoma cells arrayed along the abluminal vascular surfaces without intravasation in the sclera and/or episcleral tissue. The study included 51 women (57.3%) and 38 men with mean and median age: 63 years (range: 25-92). Mean follow-up was 4.4 years (range: 0.2 to 11). Fifty-three (59.6%) patients developed metastases and 48 (53.9%) were dead from metastases at last follow-up. Other principal variables recorded were angiotropism in 43.8%, extraocular extension in 7.9%, epithelioid/mixed cell type in 73.1%, BAP1 mutation in 41.3%, and monosomy 3 in 53.6% of cases. On multivariate analysis, extraocular extension, angiotropism, and monosomy 3 were predictive of metastasis, whereas tumor diameter, epithelioid cell type, angiotropism, and monosomy 3 were predictive of death. Chi-square test confirmed an association between angiotropism and metastasis and death but none with BAP1 mutation and monosomy 3. In conclusion, angiotropism and monosomy 3 were independent prognostic factors for both metastases and death in UM. However, irrespective of any prognostic value, the true importance of angiotropism is its biological significance as a marker of

  1. 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

  2. Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma.

    PubMed

    Nakamoto, Mitsuhiro; Matsuyama, Atsuji; Shiba, Eisuke; Shibuya, Ryo; Kasai, Takahiko; Yamaguchi, Koji; Hisaoka, Masanori

    2014-10-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P = 0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P = 0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P = 0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P = 0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.

  3. Prognostic significance of glutathione peroxidase 2 in gastric carcinoma.

    PubMed

    Liu, Dongzhe; Sun, Liang; Tong, Jinxue; Chen, Xiuhui; Li, Hui; Zhang, Qifan

    2017-06-01

    Increasing evidence suggests that the glutathione peroxidase 2 may actually play important roles in tumorigenesis and progression in various human cancers such as colorectal carcinomas and lung adenocarcinomas. However, the role of glutathione peroxidase 2 in gastric carcinoma remains to be determined. In this study, the expression and prognostic significance of glutathione peroxidase 2 in gastric carcinoma were investigated and the well-known prognostic factor Ki-67 labeling index was also assessed as positive control. Glutathione peroxidase 2 expression levels in the tumor tissue specimens, the matched adjacent normal tissue specimens, and the lymph node metastases of 176 patients with gastric carcinoma were evaluated by quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The associations between glutathione peroxidase 2 expression levels, as determined by immunohistochemical staining, and multiple clinicopathological characteristics were determined by Pearson's chi-square test and Spearman's correlation analysis. The relationships between glutathione peroxidase 2 expression and other clinicopathological variables and patient prognoses were analyzed further by the Kaplan-Meier method, the log-rank test, and Cox multivariate regression. The quantitative polymerase chain reaction, western blotting, and immunohistochemical staining results showed that glutathione peroxidase 2 expression levels were upregulated in both the primary tumor foci and the lymph node metastases of patients with gastric carcinoma (all p values < 0.05). Furthermore, Pearson's chi-square tests, as well as Spearman's correlation analysis, revealed that glutathione peroxidase 2 expression levels were strongly correlated with the Ki-67 labeling index, differentiation, histological patterns, Lauren classifications, lymph node metastasis, vascular invasion, tumor-node-metastasis stages, Helicobacter pylori infection, and overall survival (all p values

  4. Prognostic significance of the prognostic nutritional index in esophageal cancer patients undergoing neoadjuvant chemotherapy.

    PubMed

    Nakatani, M; Migita, K; Matsumoto, S; Wakatsuki, K; Ito, M; Nakade, H; Kunishige, T; Kitano, M; Kanehiro, H

    2017-08-01

    Nutritional status is one of the most important issues faced by cancer patients. Several studies have shown that a low preoperative nutritional status is associated with a worse prognosis in patients with various types of cancer, including esophageal cancer (EC). Recently, neoadjuvant chemotherapy (NAC) and/or radiotherapy have been accepted as the standard treatment for resectable advanced EC. However, NAC has the potential to deteriorate the nutritional status of a patient. This study aimed to evaluate the prognostic significance of the nutritional status for EC patients who underwent NAC. We retrospectively reviewed 66 squamous cell EC patients who underwent NAC consisting of docetaxel, cisplatin, and 5-fluorouracil followed by subtotal esophagectomy at Nara Medical University Hospital between January 2009 and August 2015. To assess the patients' nutritional status, the prognostic nutritional index (PNI) before commencing NAC and prior to the operation was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count in the peripheral blood (per mm3). The cutoff value of the PNI was set at 45. A multivariable analysis was performed to identify prognostic factors for overall survival (OS) and relapse-free survival (RFS). The mean pre-NAC and preoperative PNI were 50.2 ± 5.7 and 48.1 ± 4.7, respectively (P = 0.005). The PNI decreased following NAC in 44 (66.7%) patients. Before initiating NAC, 9 (13.6%) patients had a low PNI, and 12 (18.2%) patients had a low PNI prior to the operation. The pre-NAC PNI and preoperative PNI were significantly associated with the OS (P = 0.013 and P = 0.004, respectively) and RFS (P = 0.036 and P = 0.005, respectively) rates. The multivariable analysis identified the preoperative PNI as an independent prognostic factor for poor OS and RFS, although the pre-NAC PNI was not an independent predictor. Our results suggest that the preoperative PNI is a useful marker for predicting the long-term outcomes of EC patients

  5. 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

  6. Prognostic significance of ABCB1 in stage I lung adenocarcinoma.

    PubMed

    Zou, Fenfei; Seike, Masahiro; Noro, Rintaro; Kunugi, Shinobu; Kubota, Kaoru; Gemma, Akihiko

    2017-07-01

    Cancer stem cell (CSC) properties have been recently proposed to explain tumor carcinogenesis and multidrug resistance in several human cancers, including non-small cell lung cancer (NSCLC). The present study examined the protein expression of three CSC-associated markers, namely ATP binding cassette subfamily B member 1 (ABCB1), aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and cluster of differentiation (CD) 44, by immunohistochemistry in 194 NSCLC patients who underwent complete resection of NSCLC tumors. The association between the expression of these proteins and patient prognosis was evaluated to clarify the prognostic significance of CSC-associated markers in NSCLC patients. Positive staining for ABCB1 demonstrated a trend toward worse survival compared with negative staining in stage I-III NSCLC. Negative staining for ALDH1 or CD44 exhibited a trend toward worse survival compared with positive staining in stage I-III NSCLC. It was observed that patients with stage I lung adenocarcinoma (ADC) showing positivity for ABCB1 expression had significantly poorer survival than those with negative ABCB1 staining (P=0.03). Furthermore, stage I ADC patients with wild-type epidermal growth factor receptor (EGFR) who exhibited positive staining for ABCB1 had significantly shorter disease-free survival (DFS) compared with patients with negative staining for ABCB1 (P<0.01). Analyses by univariate and multivariate Cox proportional hazards models revealed that ABCB1-positive staining was significantly associated with DFS and was an independent prognostic factor (hazard ratio, 3.49; P<0.05) in these patients. These results suggest that ABCB1 protein expression is useful for predicting prognosis and selecting patients for post-operative therapy in stage I lung ADC patients, particularly those harboring wild-type EGFR.

  7. Clinical and prognostic significance of coagulation assays in lung cancer.

    PubMed

    Tas, Faruk; Kilic, Leyla; Serilmez, Murat; Keskin, Serkan; Sen, Fatma; Duranyildiz, Derya

    2013-03-01

    Activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are supposed to be associated with higher risk of invasion, metastases and eventually worse outcome. The aim of this study is to explore the prognostic value of blood coagulation tests for lung cancer patients. The study comprised 110 lung cancer patients. Pretreatment blood coagulation tests including PT, aPTT, PTA, INR, D-dimer, fibrinogen levels and platelet counts were evaluated. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group (p < 0.001). There was a significant association between D-Dimer levels and histological subtypes of NSCLC, pointing an elevated plasma D-dimer level in squamous cell cancer (p = 0.035). Patients with extensive stage SCLC exhibited evidently higher levels of D-Dimer, INR and PLT (p = 0.037, p = 0.042, p = 0.04, respectively). Prolongation of PT and INR had statistically significant adverse effect on survival (p = 0.05 and p = 0.014, respectively). Although prolonged aPTT and high levels of D-dimer was associated with worse survival, the difference was not statistically significant (p = 0.117, p = 0.104). Multivariate analysis revealed INR as the sole independent prognostic variable among coagulation parameters (p = 0.05). In conclusion, elevation of PT and INR are associated with decreased survival in lung cancer patients.

  8. Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma

    PubMed Central

    Bhandaru, Madhuri; Martinka, Magdalena; McElwee, Kevin J.; Rotte, Anand

    2015-01-01

    UV radiation induced genomic instability is one of the leading causes for melanoma. Phosphorylation of Ataxia Telangiectasia Mutated (ATM) is one of the initial events that follow DNA damage. Phospho-ATM (p-ATM) plays a key role in the activation of DNA repair and several oncogenic pathways as well as in the maintenance of genomic integrity. The present study was therefore performed to understand the significance of p-ATM in melanoma progression and to correlate it with patient prognosis. Tissue microarray and immunohistochemical analysis were employed to study the expression of p-ATM in melanoma patients. A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma) were used for the study. Chi-square test, Kaplan-Meier, univariate and multivariate Cox regression analysis were used to elucidate the prognostic significance of p-ATM expression. Results revealed that both loss of, and gain in, p-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma. Patients whose samples showed negative or strong p-ATM staining had significantly worse 5-year survival compared to patients who had weak to moderate expression. Loss of p-ATM expression was associated with relatively better 5-year survival, but the corresponding 10-year survival curve almost overlapped with that of strong p-ATM expression. p-ATM expression was found to be an independent prognostic factor for 5-year but not for 10-year patient survival. In conclusion our findings show that loss of p-ATM expression and gain-in p-ATM expression are indicators of worse melanoma patient survival. PMID:26275218

  9. Prognostic Significance of Nuclear Phospho-ATM Expression in Melanoma.

    PubMed

    Bhandaru, Madhuri; Martinka, Magdalena; McElwee, Kevin J; Rotte, Anand

    2015-01-01

    UV radiation induced genomic instability is one of the leading causes for melanoma. Phosphorylation of Ataxia Telangiectasia Mutated (ATM) is one of the initial events that follow DNA damage. Phospho-ATM (p-ATM) plays a key role in the activation of DNA repair and several oncogenic pathways as well as in the maintenance of genomic integrity. The present study was therefore performed to understand the significance of p-ATM in melanoma progression and to correlate it with patient prognosis. Tissue microarray and immunohistochemical analysis were employed to study the expression of p-ATM in melanoma patients. A total of 366 melanoma patients (230 primary melanoma and 136 metastatic melanoma) were used for the study. Chi-square test, Kaplan-Meier, univariate and multivariate Cox regression analysis were used to elucidate the prognostic significance of p-ATM expression. Results revealed that both loss of, and gain in, p-ATM expression were associated with progression of melanoma from normal nevi to metastatic melanoma. Patients whose samples showed negative or strong p-ATM staining had significantly worse 5-year survival compared to patients who had weak to moderate expression. Loss of p-ATM expression was associated with relatively better 5-year survival, but the corresponding 10-year survival curve almost overlapped with that of strong p-ATM expression. p-ATM expression was found to be an independent prognostic factor for 5-year but not for 10-year patient survival. In conclusion our findings show that loss of p-ATM expression and gain-in p-ATM expression are indicators of worse melanoma patient survival.

  10. Prognostic significance of peritumoral vascular invasion in breast cancer.

    PubMed Central

    Bettelheim, R.; Penman, H. G.; Thornton-Jones, H.; Neville, A. M.

    1984-01-01

    A prospective study of 232 patients with primary invasive breast cancer (UICC Stages I, II and III) and histologically confirmed axillary node status was carried out to assess the prognostic significance of several readily available clinical and pathological characteristics. In addition to the recognised utility of tumour size and axillary lymph node status, the presence or absence of cohesive clumps of malignant cells in peritumoral vascular spaces (both lymphatic and blood vessels) was found to be prognostically important. PMID:6498073

  11. 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

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

    PubMed

    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

    2014-07-14

    To investigate the prognostic significance of preoperative fibrinogen levels in colon cancer patients. A total of 255 colon cancer patients treated at the Affiliated Tumor Hospital of Xinjiang Medical University from June 1(st) 2005 to June 1(st) 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). 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 AFP levels correlated

  13. Angiogenesis: prognostic significance in laryngeal cancer.

    PubMed

    Beatrice, F; Cammarota, R; Giordano, C; Corrado, S; Ragona, R; Sartoris, A; Bussolino, F; Valente, G

    1998-01-01

    The aim of this study was to evaluate the role of angiogenesis in the progression of laryngeal squamous cell carcinoma (LSCC). We correlated disease-free survival with microvessel count (MC) in the hot spot areas of 97 randomly selected caucasian males with LSCC followed for 60 to 90 months after surgery with or without radiotherapy. The results obtained indicate that: a) MC higher than 130 microvessels/mm2 is a cut-off value that distinguished patients who relapsed during the follow up period; b) multivariated analysis indicates that MC (p < 0.00001) is an independent predictor of disease free-survival; c) multivariated analysis selectively done on cases with relapse demonstrates that MC correlates with the presence of metastasis (or/and M) with local relapse (T). We suggest that MC is useful in the assessment of prognosis in LSCC and probably will permit selection of patients that could benefit from anti-angiogenic therapy associated with chemotherapy and/or radiotherapy.

  14. Prognostic significance of PLIN1 expression in human breast cancer

    PubMed Central

    Zhou, Cefan; Wang, Ming; Zhou, Li; Zhang, Yi; Liu, Weiyong; Qin, Wenying; He, Rong; Lu, Yang; Wang, Yefu; Chen, Xing-Zhen; Tang, Jingfeng

    2016-01-01

    Breast cancer is a heterogeneous disease associated with diverse clinical, biological and molecular features, presenting huge challenges for prognosis and treatment. Here we found that perilipin-1 (PLIN1) mRNA expression is significantly downregulated in human breast cancer. Kaplan-Meier analysis indicated that patients presenting with reduced PLIN1 expression exhibited poorer overall metastatic relapse-free survival (p = 0.03). Further Cox proportional hazard models analysis revealed that the reduced expression of PLIN1 is an independent predictor of overall survival in estrogen receptor positive (p < 0.0001, HR = 0.87, 95% CI = 0.81–0.92, N = 3,600) and luminal A-subtype (p = 0.02, HR = 0.88, 95% CI = 0.78–0.98, N = 1,469) breast cancer patients. We also demonstrated that the exogenous expression of PLIN1 in human breast cancer MCF-7 and MDA-MB-231 cells significantly inhibits cell proliferation, migration, invasion and in vivo tumorigenesis in mice. Together, these data provide novel insights into a prognostic significance of PLIN1 in human breast cancer and reveal a potentially new gene therapy target for breast cancer. PMID:27359054

  15. 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

  16. 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

  17. Prognostic significance of renal vascular pathology in lupus nephritis.

    PubMed

    Mejía-Vilet, J M; Córdova-Sánchez, B M; Uribe-Uribe, N O; Correa-Rotter, R; Morales-Buenrostro, L E

    2017-01-01

    We performed a retrospective cohort analysis to define the prognostic significance of vascular lesions documented in renal biopsies of lupus nephritis patients. A total of 429 patients were segregated into five groups: (1) no vascular lesions (NVL), (2) arterial sclerosis (AS), (3) non-inflammatory necrotizing vasculitis (NNV), (4) thrombotic microangiopathy (TMA), and (5) true renal vasculitis (TRV). Renal outcomes were analyzed by Cox regression models, and correlations between vascular lesions and activity/chronicity scores were determined by Spearman's coefficients. A total of 200 (46.6%) had NVL, 189 (44.0%) AS, six NNV (1.4%), 23 (5.4%) TMA, and 11 (2.6%) TRV. Patients with NVL were younger, with higher renal function; patients with TMA and TRV had lower renal function and higher arterial pressure at baseline. Antiphospholipid syndrome and positive lupus anticoagulant were more frequently observed in the TMA group. Five-year renal survival was 83% for NVL, 63% for AS, 67% for NNV, 31% for TMA, and 33% for TRV. NNV and TRV were significantly correlated with activity scores, while AS and chronic TMA were correlated with chronicity scores. Renal vascular lesions are associated with renal outcomes but do not behave as independent factors. The addition of vascular lesions to currently used scores should be further explored.

  18. Prognostic significance of Livin expression in nasopharyngeal carcinoma after radiotherapy.

    PubMed

    Liu, A-H; He, A-B; Tong, W-X; Peng, X-L; Tian, Q; Wang, H; Li, X-G; Xu, H-L

    2016-07-01

    This study was designed to investigate the expression levels of the inhibitor of apoptosis protein Livin in nasopharyngeal cancer tissues and its prognostic significance in nasopharyngeal carcinoma after radiotherapy. A total of 83 patients with nasopharyngeal carcinoma who received radiotherapy were enrolled in this study from January 2008 to October 2010. Livin expression in nasopharynx pathological specimens extracted from patients was detected by immunohistochemistry. A Kaplan-Meier analysis was conducted to explore the effects of clinicopathological features and Livin expression on the overall survival and progression-free survival of patients with nasopharyngeal carcinoma, and explore its prognosis relevance after radiotherapy. Of the 83 patients with nasopharyngeal carcinoma, the overall Livin positive expression rate was 65.1% (54 patients), and the overall response rate of radiotherapy was 81.9% (68 patients). Significant differences in radiotherapy efficacy were found between patients who did not express Livin and those who did (P<0.05). The Kaplan-Meier analysis showed that Livin expression, high clinical staging, cervical lymph node metastasis, high T-staging and high N-staging were significantly correlated with a decrease in the overall survival of patients with nasopharyngeal carcinoma (all P<0.05). A Cox multivariate survival analysis showed that Livin expression, clinical staging and N-staging were independent risk factors for the overall survival of patients with nasopharyngeal carcinoma treated with radiation (all P<0.05). Furthermore, Livin expression and clinical staging were independent risk factors for the progression-free survival of patients with nasopharyngeal carcinoma once radiotherapy was introduced (all P<0.05). Expression of Livin, an inhibitor of apoptosis proteins, may be closely linked with poor prognosis of nasopharyngeal carcinoma post-radiotherapy and hence it may be a new therapeutic target in the treatment of the disease

  19. BLZF1 expression is of prognostic significance in hepatocellular carcinoma

    SciTech Connect

    Huang, Run-Yue; Su, Shu-Guang; Wu, Dan-Chun; Fu, Jia; Zeng, Xing

    2015-11-20

    BLZF1, a member of b-ZIP family, has been implicated in epigenetic regulation and Wnt/β-catenin signaling. Its expression and clinical significance in human cancers remain largely unknown. In this study, we showed that BLZF1 expression was reduced in hepatocellular carcinoma (HCC) tissues, compared to the paracarcinoma tissues, at both mRNA and protein levels. Results of immunohistochemistry revealed that BLZF1 was presented in both nuclear and cytoplasm. Decreased expression of nuclear and cytosolic BLZF1 in HCC was depicted in 68.2% and 79.2% of the 634 cases. Nuclear BLZF1 expression was significantly associated with tumor multiplicity (P = 0.048) and tumor capsule (P = 0.028), while cytosolic BLZF1 expression was correlated with serum AFP level (P = 0.017), tumor differentiation (P = 0.001) and tumor capsule (P = 0.003). Kaplan–Meier analysis indicated both nuclear and cytosolic BLZF1 expression was associated with poor overall survival. Low nuclear BLZF1 also indicated unfavorable disease-free survival and high tendency of tumor recurrence. Furthermore, multiple Cox regression analysis revealed nuclear BLZF1 as an independent factor for overall survival (Hazard Ratio (HR) = 0.827, 95% confident interval (95%CI): 0.697–0.980, P = 0.029). The prognostic value of BLZF1 was further confirmed by stratified analyses. Collectively, our data suggest BLZF1 is a novel unfavorable biomarker for prognosis of patients with HCC. - Highlights: • BLZF1 expression was much lower in HCC tissues. • Low BLZF1 expression was associated with poor outcomes in a cohort of 634 HCC patients. • Multiple Cox regression analysis indicated nuclear BLZF1 as an independent predictor for overall survival.

  20. Exo70 is an independent prognostic factor in colon cancer.

    PubMed

    Xiao, Li; Zheng, Kaifeng; Lv, Xia; Hou, Jihuan; Xu, Liang; Zhao, Yujie; Song, Fei; Fan, Yaqiong; Cao, Hanwei; Zhang, Wenqing; Hong, Xiaoting; Zhan, Yan-Yan; Hu, Tianhui

    2017-07-11

    Exo70, a key component of the Exocyst complex, plays important roles in human cancer progression beyond exocytosis. However, the expression of Exo70 and its prognostic value for patients with colon cancer has not been well investigated to date. In this study, we observed that the mRNA and protein levels of Exo70 were upregulated in 11 of 13 colon cancer tissues, compared with their normal counterparts, which was validated by immunohistochemical analysis in a tissue microarray containing 89 pairs of colon cancer tissues and the matched adjacent normal tissues. Statistical analysis revealed that Exo70 expression is positively correlated with tumor size, invasion depth, TNM stage and distant metastasis. Kaplan-Meier survival analysis showed that colon cancer patients with higher Exo70 expression have a poorer clinical outcome than those with lower Exo70 expression. Multivariate Cox regression analysis revealed that Exo70, age and distant metastasis were there independent prognostic factors for overall survival rate of colon cancer patients. Through gain- and loss of Exo70 in colon cancer cells, we found that Exo70 could enhance the migration ability of colon cancer cells. Taken together, our studies revealed that Exo70 might be a promising negative prognostic factor and a potential therapeutic target for colon cancer.

  1. Prognostic significance of tumour stroma ratio in inflammatory breast cancer.

    PubMed

    Downey, Candice L; Thygesen, Helene H; Sharma, Nisha; Shaaban, Abeer M

    2015-01-01

    Tumour stroma ratio (TSR) is emerging as an important prognostic indicator in cancer. We have previously shown TSR to be prognostic in oestrogen receptor positive breast cancer. Its role in inflammatory breast cancer, a rare but aggressive form of breast cancer, has not been identified. Here we aimed to determine the prognostic significance of TSR in a cohort of patients with inflammatory breast carcinoma. TSR was measured by point counting virtual H&E stained tissue sections in 45 inflammatory breast cancer cases. The whole tumour area was sampled. Optimum cut-offs to distinguish high and low TSR was determined by log-rank test. The relationship of TSR to overall survival and disease-free survival (DFS) was analysed alongside multivariate analysis. The optimal cut-offs between high and low TSR were determined to be 31% for OS and 46% for DFS. There was no significant difference in OS (p = 0.53) nor DFS (p = 0.66) between high and low TSR groups. Multivariate analysis did not demonstrate any new trends, within the limits of a small data sample. A significant correlation was found between pathological response to neoadjuvant chemotherapy and survival (p = 0.008). There is no evidence that TSR has prognostic significance in inflammatory breast cancer. When compared with published data in non-inflammatory breast carcinoma, this supports the view that differences in stromal biology exist between tumour types and highlights the importance of considering this when interpreting the prognostic value of TSR. However, these findings must be interpreted in the light of the small sample size.

  2. 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. © 2016 UICC.

  3. Lack of prognostic significance of angiogenesis in canine melanocytic tumours.

    PubMed

    Cuitiño, M C; Massone, A R; Idiart, J R

    2012-01-01

    The prognostic significance of angiogenesis in some canine tumours has been investigated, but little is known about its relevance in canine melanocytic tumours (MTs). The aim of this study was to evaluate the prognostic significance of angiogenesis in canine MTs. A total of 36 cutaneous melanocytomas (benign MTs), 40 cutaneous melanomas (malignant MTs) and 43 oral melanomas were studied. Survival data were available for a subset of 59 cases. Microvessel density (MVD) and endothelial area (EA) were determined by immunolabelling using an antibody specific for von Willebrand factor (vWF). Mean MVD (expressed as the number of microvessels per mm(2)) was 129 ± 14 in melanocytomas, 191 ± 16 in cutaneous melanomas and 208 ± 16 in oral melanomas. Mean EA (expressed as the percentage of the total area) was 1.5 ± 0.14 in melanocytomas, 2.6 ± 0.2 in cutaneous melanomas and 2.4 ± 0.3 in oral melanomas. The differences in MVD and EA between melanocytomas and melanomas were significant (P = 0.001 and P = 0.003, respectively). MVD and EA were significantly correlated between cutaneous and oral MTs (r = 0.54; P <0.001 and r = 0.63; P <0.001, respectively). MVD and EA were not related to survival in cutaneous and oral MTs. In conclusion, tumour vascularization was higher in melanomas than in melanocytomas, but it seemed to have no prognostic significance in these tumours. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Frailty in Chinese Peritoneal Dialysis Patients: Prevalence and Prognostic Significance.

    PubMed

    Ng, Jack Kit-Chung; Kwan, Bonnie Ching-Ha; Chow, Kai-Ming; Cheng, Phyllis Mei-Shan; Law, Man-Ching; Pang, Wing-Fai; Leung, Chi-Bon; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

    2016-01-01

    Previous studies showed that frailty is prevalent in both pre-dialysis and dialysis patients. However, the prevalence and prognostic implication of frailty in Chinese peritoneal dialysis (PD) patients remain unknown. We used a validated questionnaire to determine the Frailty Score of 193 unselected prevalent PD patients. All patients were then followed for 2 years for their need of hospitalization and mortality. Amongst the 193 patients, 134 (69.4%) met the criteria of being frail. Frailty Score significantly correlated with Charlson's comorbidity score (r = 0.40, p < 0.0001), Malnutrition Inflammation Score (r = 0.59, p < 0.0001), and inversely with Subjective Global Assessment score (r = -0.44, p < 0.0001). Frailty was closely associated with the need of hospitalization. Patients with nil, mild, moderate, and severe frailty required 2.4 ± 6.0, 1.6 ± 1.6, 2.7 ± 2.5, 5.2 ± 4.8 hospital admissions per year, respectively (p < 0.0001), and they stayed in hospital for 6.4 ± 9.2, 5.3 ± 6.2, 10.0 ± 10.4, 12.9 ± 20.1 days per hospital admission, respectively (p < 0.0001). However, Frailty Score was not an independent predictor of patient or technique survival. Frailty is prevalent among Chinese PD patients. Frail PD patients have a high risk of requiring hospitalization and their hospital stay tends to be prolonged. Early identification may allow timely intervention to prevent adverse health outcomes in this group of patients. © 2016 The Author(s) Published by S. Karger AG, Basel.

  5. The Significance of the Prognostic Nutritional Index in Patients with Completely Resected Non-Small Cell Lung Cancer

    PubMed Central

    Mori, Shunsuke; Usami, Noriyasu; Fukumoto, Koichi; Mizuno, Tetsuya; Kuroda, Hiroaki; Sakakura, Noriaki; Yokoi, Kohei; Sakao, Yukinori

    2015-01-01

    Objectives Immunological parameters and nutritional status influence the outcome of patients with malignant tumors. A prognostic nutritional index, calculated using serum albumin levels and peripheral lymphocyte count, has been used to assess prognosis for various cancers. This study aimed to investigate whether this prognostic nutritional index affects overall survival and the incidence of postoperative complications in patients with completely resected non-small cell lung cancer. Methods We retrospectively reviewed the medical records of 409 patients with non-small cell lung cancer who underwent complete resection between 2005 and 2007 at the Aichi Cancer Center. Results The 5-year survival rates of patients with high (≥50) and low (<50) prognostic nutritional indices were 84.4% and 70.7%, respectively (p = 0.0011). Univariate analysis showed that gender, histology, pathological stage, smoking history, serum carcinoembryonic antigen levels, and prognostic nutritional index were significant prognostic factors. Multivariate analysis identified pathological stage and the prognostic nutritional index as independent prognostic factors. The frequency of postoperative complications tended to be higher in patients with a low prognostic nutritional index. Conclusions The prognostic nutritional index is an independent prognostic factor for survival of patients with completely resected non-small cell lung cancer. PMID:26356222

  6. Methylation of serum SST gene is an independent prognostic marker in colorectal cancer

    PubMed Central

    Liu, Yanqun; Chew, Min Hoe; Tham, Chee Kian; Tang, Choong Leong; Ong, Simon YK; Zhao, Yi

    2016-01-01

    There is an increasing demand for accurate prognostication for colorectal cancer (CRC). This study sought to assess prognostic potentials of methylation targets in the serum of CRC patients. A total of 165 CRC patients were enrolled in this prospective study. Promoter methylation levels of seven genes in pre-operative sera and matched tumor tissues were evaluated by quantitative methylation-specific PCR. Kaplan-Meier test, and univariate and multivariate Cox proportional hazards regression models were used for survival analyses. After a median follow-up of 56 months, 43 patients (28.7%) experienced tumor recurrence. In univariate survival analyses, serum methylation levels of SST and MAL were significantly predictive of cancer-specific death (P<0.005 for both). The former was also a significant predictor for tumor recurrence (P=0.007). Independent prognostic effects of serum methylation levels of SST were revealed by multivariate Cox regression model (P=0.031 and P=0.003 for cancer death and recurrence, respectively). When focusing on stage II and III patients, prognostication with serum methylated SST remained significant. Methylated SST detected in all serum samples can be traced back to the matched primary tumor tissues. We believe that methylated SST detected in the pre-operative sera of CRC patients appear to be a novel promising prognostic marker and probably can be auxiliary to tumor staging system and serum carcinoembryonic antigen towards better risk stratification. PMID:27725914

  7. Methylation of serum SST gene is an independent prognostic marker in colorectal cancer.

    PubMed

    Liu, Yanqun; Chew, Min Hoe; Tham, Chee Kian; Tang, Choong Leong; Ong, Simon Yk; Zhao, Yi

    2016-01-01

    There is an increasing demand for accurate prognostication for colorectal cancer (CRC). This study sought to assess prognostic potentials of methylation targets in the serum of CRC patients. A total of 165 CRC patients were enrolled in this prospective study. Promoter methylation levels of seven genes in pre-operative sera and matched tumor tissues were evaluated by quantitative methylation-specific PCR. Kaplan-Meier test, and univariate and multivariate Cox proportional hazards regression models were used for survival analyses. After a median follow-up of 56 months, 43 patients (28.7%) experienced tumor recurrence. In univariate survival analyses, serum methylation levels of SST and MAL were significantly predictive of cancer-specific death (P<0.005 for both). The former was also a significant predictor for tumor recurrence (P=0.007). Independent prognostic effects of serum methylation levels of SST were revealed by multivariate Cox regression model (P=0.031 and P=0.003 for cancer death and recurrence, respectively). When focusing on stage II and III patients, prognostication with serum methylated SST remained significant. Methylated SST detected in all serum samples can be traced back to the matched primary tumor tissues. We believe that methylated SST detected in the pre-operative sera of CRC patients appear to be a novel promising prognostic marker and probably can be auxiliary to tumor staging system and serum carcinoembryonic antigen towards better risk stratification.

  8. Tumor budding is an independent adverse prognostic factor in pancreatic ductal adenocarcinoma.

    PubMed

    O'Connor, Kate; Li-Chang, Hector H; Kalloger, Steven E; Peixoto, Renata D; Webber, Douglas L; Owen, David A; Driman, David K; Kirsch, Richard; Serra, Stefano; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-04-01

    Tumor budding is a well-established adverse prognostic factor in colorectal cancer. However, the significance and diagnostic reproducibility of budding in pancreatic carcinoma requires further study. We aimed to assess the prognostic significance of tumor budding in pancreatic ductal adenocarcinoma, determine its relationship with other clinicopathologic features, and assess interobserver variability in its diagnosis. Tumor budding was assessed in 192 archival cases of pancreatic ductal adenocarcinoma using hematoxylin and eosin (H&E) sections; tumor buds were defined as single cells or nonglandular clusters composed of <5 cells. The presence of budding was determined through assessment of all tumor-containing slides, and associations with clinicopathologic features and outcomes were analyzed. Six gastrointestinal pathologists participated in an interobserver variability study of 120 images of consecutive tumor slides stained with H&E and cytokeratin. Budding was present in 168 of 192 cases and was associated with decreased overall survival (P=0.001). On multivariable analysis, tumor budding was prognostically significantly independent of stage, grade, tumor size, nodal status, lymphovascular invasion, and perineural invasion. There was substantial agreement among pathologists in assessing the presence of tumor budding using both H&E (K=0.63) and cytokeratin (K=0.63) stains. The presence of tumor budding is an independent adverse prognostic factor in pancreatic ductal carcinoma. The assessment of budding with H&E is reliable and could be used to better risk stratify patients with pancreatic ductal adenocarcinoma.

  9. Prevalence, characteristics and prognostic significance of anemia in daily practice.

    PubMed

    Terrier, B; Resche-Rigon, M; Andres, E; Bonnet, F; Hachulla, E; Marie, I; Rosenthal, E; Cacoub, P

    2012-04-01

    The prevalence of anemia has been studied in well-defined populations, but no large study is available for less restricted populations with various disorders. Two-phase nationwide study: (i) a cross-sectional study including 1351 patients aimed to define the prevalence and characteristics of anemic patients seen in France, and (ii) a prospective longitudinal study of 398 anemic patients aimed to define factors associated with survival. Anemia was present in 874 (65%) patients according to WHO criteria, and 573 (42%) patients had hemoglobin levels <110 g/l. Characteristics independently associated with anemia were the presence of cancer, hematological disorder, renal failure and inflammatory syndrome. Baseline factors negatively associated with the 3-month survival were cancer, older age and a lower target hemoglobin level defined at baseline. Negative predictive factors at Month 3 of the 6-month survival were older age and the absence of correction of anemia according to the target hemoglobin level defined at baseline. Anemia is frequent and is associated with cancer, hematological disorders, renal failure and inflammatory syndrome. At baseline, prognostic factors of 3-month survival include cancer, older age and lower target hemoglobin level, whereas reaching the target hemoglobin level at Month 3 has a favorable prognostic impact on 6-month survival.

  10. Prognostic significance of KLF4 expression in gastric cancer

    PubMed Central

    Hashimoto, Isaya; Nagata, Takuya; Sekine, Shinichi; Moriyama, Makoto; Shibuya, Kazuto; Hojo, Shozo; Matsui, Koshi; Yoshioka, Isaku; Okumura, Tomoyuki; Hori, Takashi; Shimada, Yutaka; Tsukada, Kazuhiro

    2017-01-01

    To understand the roles of pluripotent stem cell-inducing genes in gastric cancer, the expression of Krüppel-like factor 4 (KLF4), Nanog, octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc) and sex-determining region Y-box 2 (SOX2) was examined using the newly developed gastric carcinoma tissue microarray. The associations between the immunohistochemical expression levels of the pluripotency-inducing factors and the clinicopathological data of 108 patients with gastric cancer were analyzed. No associations were identified between the expression levels of the five pluripotency-inducing factors and the tumor-node-metastasis (TNM) classification or clinicopathological characteristics of the patients. In addition, multivariate analysis revealed no association of Nanog, Oct4, SOX2 or c-Myc with the prognosis of the gastric cancer patients; however, low expression of KLF4 was determined to be an independent negative prognostic factor (P=0.0331), particularly in patients who underwent R0 resection (TNM stages 2 and 3; P=0.0048). In summary, low KLF4 expression was found to be negatively associated with overall survival, and may therefore be a useful prognostic marker in gastric cancer patients. PMID:28356964

  11. Prognostic significance of selected lifestyle factors in urinary bladder cancer.

    PubMed

    Wakai, K; Ohno, Y; Obata, K; Aoki, K

    1993-12-01

    To examine the prognostic significance of lifestyle factors in urinary bladder cancer, we conducted a follow-up study of 258 incident bladder cancer patients, who were originally recruited in a case-control study in metropolitan Nagoya. Information on individual survivals was obtained from the computer data-file of the tumor registry of the Nagoya Bladder Cancer Research Group. Univariate analyses revealed significant associations of 5-year survivorship with educational attainment, marital status, drinking habits and consumption of green tea in males, and age at first consultation, histological type and grade of tumor, stage and distant metastasis in both sexes. After adjustment for age, stage, histology (histological type and grade) and distant metastasis by means of a proportional hazards model, drinking of alcoholic beverages was significantly associated with the prognosis of bladder cancer in males. Its adjusted hazard ratio was 0.46 (95% confidence interval: 0.26-0.79), favoring patients who had taken alcoholic beverages. In detailed analysis, ex-drinkers and all levels of current drinkers demonstrated hazard ratios smaller than unity, although no clear dose-response relationship was detected. No prognostic significance was found for such lifestyle factors as smoking habit, uses of artificial sweeteners and hairdye, and consumption of coffee, black tea, matcha (powdered green tea) and cola.

  12. Prognostic significance of nucleolar organizer regions (NORS) in malignant melanoma.

    PubMed

    Ronan, S G; Farolan, M J; McDonald, A; Manaligod, J R; Das Gupta, T K

    1994-12-01

    Nucleolar organizer regions (NORs) are loops of ribosomal DNA (rDNA) in the nucleolus and are associated with acidic proteins. They are seen in routinely processed paraffin sections by using a one-step colloidal silver (Ag) staining method; they appear as black dots termed "AgNORs". The quantitative assay of AgNORs has been used to differentiate benign from malignant neoplasms. Melanocytic lesions differ significantly in AgNOR counts between malignant melanoma and nevi. However, conflicting results have been reported as to AgNORs' prognostic value in melanoma. A recent study showed AgNOR counts to be a more accurate prognostic indicator than Breslow's thickness. In this study, we counted the AgNORs in 26 patients with primary cutaneous melanomas (CMM) between 2.0 mm and 2.5 mm thick. Of these, 14 are alive without disease (AN) at 5 years after diagnosis (group 1) and 12 are dead of disease (DD) in less than 5 years (group 2). The AgNORs were scored in 30 nuclei per tumor, and the means were calculated. For group 1, the mean number of AgNORs per nucleus was 6.88, ranging from 3.73 to 12.70. For group 2, the mean number was 6.97, ranging from 3.63 to 11.67. Statistical analysis using analysis of variance (ANOVA) showed no significant difference between the groups (p = 0.33). In our study, AgNOR counts did not prove to be of prognostic value in malignant melanoma.

  13. Prognostic significance of platelet count in SLE patients.

    PubMed

    Abdel Galil, Sahar Mahfouz; Edrees, Azzahra Mohammed; Ajeeb, Afnan Khaled; Aldoobi, Ghadeer Sameer; El-Boshy, Mohamed; Hussain, Waleed

    2017-03-01

    Hematological abnormalities, especially thrombocytopenia (TCP), are highly prevalent among patients with systemic lupus erythematosus (SLE) and at the same time it has been reported as a significant prognostic factor of SLE course. We further investigate the correlation between platelet count and the clinical manifestations and disease activity of SLE, in a cohort of Saudi Arabian female patients. A retrospective analysis was done for the medical records of 100 SLE female patients, selected from all patients diagnosed and treated for SLE at the Rheumatology outpatient clinics in Hera'a General Hospital, Holly Makkah, Saudi Arabia. The data collected from every patient's file included laboratory investigations (complete blood count, platelet parameters, ESR, anti-double-stranded DNA antibody, ANA), clinical manifestations, as well as SLE disease activity index (SLEDAI-2k) scores throughout a period of six sequential follow-up visits. Patients were divided into three groups according to the SLEDAI-2k: mild, moderate, and high-activity group. We found that, out of 100 patients, TCP was the most prevalent hematological abnormality evident in 15%, more than leucopenia (14%) and anemia (2%). TCP was acute in onset and associated with arthritis, neurologic manifestations, and nephritis. Platelet count showed a significant negative correlation with disease activity, in all of the three groups of patients. We concluded that platelet count has a negative correlation with disease activity in SLE patients, whatever the associated manifestations, and it should be considered as a prognostic factor, identifying patients with aggressive disease course.

  14. Telomere length is an independent prognostic marker in MDS but not in de novo AML.

    PubMed

    Williams, Jenna; Heppel, Nicole H; Britt-Compton, Bethan; Grimstead, Julia W; Jones, Rhiannon E; Tauro, Sudhir; Bowen, David T; Knapper, Steven; Groves, Michael; Hills, Robert K; Pepper, Chris; Baird, Duncan M; Fegan, Chris

    2017-07-01

    Telomere dysfunction is implicated in the generation of large-scale genomic rearrangements that drive progression to malignancy. In this study we used high-resolution single telomere length analysis (STELA) to examine the potential role of telomere dysfunction in 80 myelodysplastic syndrome (MDS) and 95 de novo acute myeloid leukaemia (AML) patients. Despite the MDS cohort being older, they had significantly longer telomeres than the AML cohort (P < 0·0001) where telomere length was also significantly shorter in younger AML patients (age <60 years) (P = 0·02) and in FLT3 internal tandem duplication-mutated AML patients (P = 0·03). Using a previously determined telomere length threshold for telomere dysfunction (3·81 kb) did not provide prognostic resolution in AML [Hazard ratio (HR) = 0·68, P = 0·2]. In contrast, the same length threshold was highly prognostic for overall survival in the MDS cohort (HR = 5·0, P < 0·0001). Furthermore, this telomere length threshold was an independent parameter in multivariate analysis when adjusted for age, gender, cytogenetic risk group, number of cytopenias and International Prognostic Scoring System (IPSS) score (HR = 2·27, P < 0·0001). Therefore, telomere length should be assessed in a larger prospective study to confirm its prognostic role in MDS with a view to integrating this variable into a revised IPSS. © 2017 John Wiley & Sons Ltd.

  15. Prognostic significance of WT1 expression in soft tissue sarcoma

    PubMed Central

    2014-01-01

    Background Soft tissue sarcomas (STS) are rare. We evaluated the WT1 protein expression level in various types of STS and elucidated the value of WT1 as a prognostic factor and a possible therapeutic target. Methods Immunohistochemical staining for WT1 was performed in 87 cases of STS using formalin-fixed, paraffin-embedded blocks. The correlation between WT1 expression and clinicopathological factors was analyzed. Survival analysis was conducted in 67 patients. We assessed the validity of WT1 immunohistochemistry as an index of WT1 protein expression using Western blot analysis. Results WT1 expression was noted in 47 cases (54.0%). Most rhabdomyosarcomas and malignant peripheral nerve sheath tumors showed WT1 expression (91.7% and 71.4%, respectively; P = 0.005). WT1 expression was related to higher FNCLCC histologic grade and AJCC tumor stage. In the group with high grade STS, strong WT1 expression was correlated with better survival (P = 0.025). The immunohistochemical results were correlated quantitatively with the staining score and the concentration of the Western blot band. Conclusions This study demonstrates that various types of STS show positive immunostaining for WT1 and that WT1 expression has a prognostic significance. So STS should be considered candidates for WT1 peptide--based immunotherapy. PMID:25026998

  16. Clinical and prognostic significance of hyperfibrinogenemia in cerebral ischemia.

    PubMed

    D'Erasmo, E; Pisani, D; Romagnoli, S; Ragno, A; Acca, M

    1998-01-01

    In order to evaluate the clinical and prognostic significance of early hyperfibrinogenemia in patients with transient ischemic attack (TIA) and ischemic cerebral infarction (ICI), we analyzed the relationships between plasma fibrinogen, brain damage severity, clinical status on admission and intra-hospital mortality. Vascular damage severity was estimated by measuring the necrotic area by computed axial tomography (CT) and indirectly by means of changes in some plasma enzymes (CK, LDH, GPT/ALT, and GOT/AST). Plasma fibrinogen levels were statistically higher in ICI than in TIA and control subjects (p < 0.0005; analysis of variance). Moreover, plasma fibrinogen was directly related to the extension of the necrotic area at CT scan (p < 0.05) and in ICI patients was positively correlated with CK (r = 0.50, p < 0.01), LDH (r = 0.41, p < 0.05) and GOT/AST (r = 0.42, p < 0.05) serum levels, but not with GPT/ALT. A higher plasma fibrinogen value was observed in patients with stupor or coma compared with those with alert consciousness (p < 0.05). In patients who died during hospitalization, fibrinogen levels were higher than those of subjects who were discharged (p < 0.005). The results indicate that in the early phase of cerebral ischemia, plasma fibrinogen levels are related to the severity of the clinical status and to the extension of the brain vascular damage, thus representing a negative clinical and prognostic factor of the disease.

  17. Prognostic significance of the preoperative lymphocyte-to-monocyte ratio in patients with colorectal cancer

    PubMed Central

    Shibutani, Masatsune; Maeda, Kiyoshi; Nagahara, Hisashi; Iseki, Yasuhito; Ikeya, Tetsuro; Hirakawa, Kosei

    2017-01-01

    A correlation between the lymphocyte-to-monocyte ratio (LMR) and the survival of patients with hematological malignancies has been reported previously. However, there have been few studies investigating the prognostic significance of LMR in patients with solid tumors. The aim of the present study was to evaluate the prognostic significance of preoperative LMR in patients with colorectal cancer (CRC). A total of 189 patients undergoing potentially curative surgery for CRC were enrolled. The LMR was calculated from preoperative blood samples by dividing absolute lymphocyte count by absolute monocyte count. A cut-off value of 4.8 was set based on the receiver operating characteristic curve; 116 patients were classified as high-LMR, and 73 patients classified as low-LMR. The high-LMR group exhibited significantly better relapse-free survival (P=0.0018) and overall survival (P=0.0127) rates than the low-LMR group. According to the multivariate analysis of survival, preoperative LMR was identified as an independent prognostic factor for relapse-free survival (P=0.041) and overall survival (P=0.031). Therefore, preoperative LMR is a useful prognostic marker in patients with CRC.

  18. CD9 Expression in Colorectal Carcinomas and Its Prognostic Significance

    PubMed Central

    Kim, Kyung-Ju; Kwon, Hee Jung; Kim, Min Chong; Bae, Young Kyung

    2016-01-01

    Background CD9, a member of the tetraspanin superfamily, is a tumor suppressor in many malignancies. The aim of this study was to evaluate the immunohistochemical expression of CD9 in colorectal carcinomas (CRCs) and determine clinicopathological and prognostic significance of its expression. Methods The CD9 expression status of 305 CRCs was evaluated using a semi-quantitative scoring system in tumor cells (T-CD9) and immune cells (I-CD9) by classifying the results as high and low expression. Results High T-CD9 (T-CD9 [+]) expression was detected in 175 samples (57.6%) and high I-CD9 (I-CD9 [+]) expression was detected in 265 samples (86.9%). Using Kaplan-Meier survival analysis, the T-CD9 (+) group showed a tendency for better disease-free survival (DFS) (p = .057). In left-sided tumors, DFS was significantly longer in the T-CD9 (+) group (p = .021) but no statistical significance was observed with right-sided tumors (p = .453). I-CD9 (+) CRCs significantly correlated with well/moderately differentiation (p = .014). In Kaplan-Meier analysis, the I-CD9 (+) group had a tendency towards worse DFS compared to the I-CD9 (–) group (p = .156). In combined survival analysis of T-CD9 and I-CD9, we found that the longest DFS was among patients in the T-CD9 (+)/I-CD9 (–) group, whereas the T-CD9 (–)/I-CD9 (+) group showed the shortest DFS (p = .054). Conclusions High expression of T-CD9 was associated with a favorable DFS, especially in left-sided CRCs. Combined evaluation of T-CD9 and I-CD9 is required to determine the comprehensive prognostic effect of CD9 in CRCs. PMID:27780340

  19. 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

  20. The prognostic significance of nutritional status using malnutrition universal screening tool in patients with pulmonary tuberculosis.

    PubMed

    Miyata, Shigeru; Tanaka, Mikio; Ihaku, Daizo

    2013-04-08

    Malnutrition is frequently observed in patients with pulmonary tuberculosis (TB). The present study aimed to examine the relationship between nutritional status using Malnutrition Universal Screening Tool (MUST) and the mortality of patients with pulmonary TB. Fifty-seven patients with pulmonary TB were analyzed. Nutrition assessment was carried out using MUST. The Cox proportional hazard model was applied to assess the ability of MUST to predict prognosis. Receiver operating characteristic curve analysis was used to assess MUST score as a prognostic indicator in pulmonary TB patients. To obtain optimal cut-off values for MUST score for prognostic assessment in TB patients, we used the maximum Youden Index. For predicting the risk of mortality, the optimal cut-off value for MUST score was 3.5. Univariate and multivariate analyses identified age and MUST score ≥ 4 as significant independent prognostic factors for survival. The patients with MUST score ≤ 3 had a median survival of 481 days (95% CI: 453 to 510) and that for the patients with MUST score ≥ 4 was 304 days (95% CI: 214 to 394); the difference was statistically significant (P = 0.001). MUST appears to be a reliable tool for nutritional risk assessment of patients with pulmonary TB. In addition, MUST may be a useful prognostic indicator of survival in patients with pulmonary TB.

  1. Prognostic Significance of Venous Thromboembolic Events in Disseminated Germ Cell Cancer Patients.

    PubMed

    Gonzalez-Billalabeitia, Enrique; Castellano, Daniel; Sobrevilla, Nora; Guma, Josep; Hervas, David; Luengo, Maria I; Aparicio, Jorge; Sanchez-Muñoz, Alfonso; Mellado, Begoña; Saenz, Alberto; Valverde, Claudia; Fernandez, Antonio; Margeli, Mireia; Duran, Ignacio; Fernandez, Sara; Sastre, Javier; Ros, Silverio; Maroto, Pablo; Manneh, Ray; Cerezuela, Pablo; Carmona-Bayonas, Alberto; Ayala de la Peña, Francisco; Aguilar, Jose Luis; Rivera, Samuel; García del Muro, Xavier; Germà-Lluch, Jose R

    2017-01-01

    Disseminated germ cell cancers are at high risk of developing thromboembolic complications. We evaluated the prognostic value of venous thromboembolic events (VTE) in disseminated germ cell cancer. Patients with germ cell cancer receiving upfront platinum-containing chemotherapy between 2004 and 2014 were pooled from the Spanish Germ Cell Cancer Group (SGCCG) registry and reviewed for the presence of VTE. Results were validated in an independent international group of patients. We used a penalized Cox proportional hazards model including VTE as a time-varying covariate to identify and validate prognostic factors. All statistical tests were two-sided. The SGCCG registry identified 416 patients from 14 referral institutions. With a median follow-up of 49 months, VTEs were observed in 9% of patients (n = 38). Events occurred at diagnosis, during chemotherapy, and after chemotherapy in 2.6%, 5.0%, and 1.4% of patients, respectively. VTE was associated with shorter progression-free survival (PFS; hazard ratio [HR] = 2.29, 95% confidence interval [CI] = 1.18 to 4.47, P = .02) and overall survival (OS; HR = 5.14, 95% CI = 2.22 to 11.88, P < .001). In multivariable analysis, the effect was consistent in the intermediate-risk group, both for PFS (HR = 9.52 95% CI = 2.48 to 36.58, P < .001) and OS (HR = 12.84, 95% CI = 2.01 to 82.02, P = .007). VTE at diagnosis is also an adverse prognostic variable for progression-free survival (HR = 4.64, 95% CI = 2.04 to 10.54, P < .001) and for overall survival (HR = 6.28, 95% CI = 1.68 to 17.10, P = .01). These results were validated in an independent international cohort that included 241 patients from four hospitals. VTE is an independent adverse prognostic factor in disseminated germ cell cancers, in particular for the intermediate prognostic group of the International Germ Cell Cancer Collaborative Group classification. The presence of VTE at diagnosis has also prognostic significance and

  2. 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. PMID:27621848

  3. Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma.

    PubMed

    Kübler, Kirsten; Ayub, Tiyasha H; Weber, Sarah K; Zivanovic, Oliver; Abramian, Alina; Keyver-Paik, Mignon-Denise; Mallmann, Michael R; Kaiser, Christina; Serçe, Nuran Bektas; Kuhn, Walther; Rudlowski, Christian

    2014-11-01

    Endometrial adenocarcinoma is one of the most common gynecologic malignancies worldwide and in stages confined to the uterus considered to have an excellent prognosis. However, in advanced or recurrent cases when surgery fails to achieve disease control other treatment options are less effective. Thus, new therapeutic avenues are needed. To provide the rationale for the use of novel agents that target immune checkpoints 163 type I endometrial cancer samples were immunohistochemically screened for the presence of CD163(+) tumor-associated macrophages and Foxp3(+) regulatory T cells. Further, a D2-40-based evaluation of lymph vessel density and lymphovascular space invasion was carried out. Correlation analysis with clinicopathological parameters was performed; Kaplan-Meier curves were generated; multivariate analysis was undertaken as appropriate. A substantial amount of tumor-associated macrophages and regulatory T cells was detected in all specimens characterizing endometrial cancer as an immunogenic tumor. However, only the increased infiltration of tumor-associated macrophages was proportionally associated with advanced FIGO stages, high tumor grade, increased lymph vessel density, lymphovascular space invasion and lymph node metastasis. Thus, the presence of tumor-associated macrophages indicates aggressive tumor behavior and appeared to be an independent prognostic factor for recurrence-free survival. Our results make future therapeutic approaches that target tumor-associated macrophages reasonable to improve the outcome of women with advanced or recurrent endometrial adenocarcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Do pathological variables have prognostic significance in rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and surgery?

    PubMed Central

    Reggiani Bonetti, Luca; Lionti, Simona; Domati, Federica; Barresi, Valeria

    2017-01-01

    AIM To clarify which factors may influence pathological tumor response and affect clinical outcomes in patients with locally advanced rectal carcinoma treated with neo-adjuvant chemoradiotherapy and surgery. METHODS Tumor regression grade (TRG) according to the Dworak system and yTNM stage were assessed and correlated with pre-treatment clinico-pathological variables in 215 clinically locally advanced (cTNM stage II and III) rectal carcinomas. Prognostic value of all pathological and clinical factors on disease free survival (DFS) and cancer specific survival (CSS) was analyzed by Kaplan Meier and Cox-regression analyses. RESULTS cN+ status, mucinous histotype or poor differentiation in the pre-treatment biopsy were significantly associated with lower pathological response (low Dworak grade and TNM remaining unchanged/upstaging). Cases showing acellular mucin pools in surgical specimens all had unremarkable clinical courses with no deaths or recurrences during follow-up. Dworak grade had prognostic significance for DFS and CSS. However, compared to the 5-tiered system, a simplified two-tiered grading system, in which grades 0, 1 and 2 were grouped as absent/partial regression and grades 3 and 4 were grouped as total/subtotal regression, was more reproducible and prognostically informative. The two-tiered Dworak system, yN stage, craniocaudal extension of the tumor and radial margin status were significant independent prognostic variables. CONCLUSION Our data suggest that caution should be applied in using a conservative approach in rectal carcinomas with cN+ status, extensive/lower involvement of the rectum and mucinous histotype or poor differentiation. Although Dworak TRG is prognostically significant, a simplified two-tiered system could be preferable. Finally, cases with acellular mucin pools should be carefully evaluated to definitely exclude residual mucinous carcinoma. PMID:28293088

  5. L1 cell adhesion molecule as a novel independent poor prognostic factor in gallbladder carcinoma.

    PubMed

    Choi, Song-Yi; Jo, Young Suk; Huang, Song-Mei; Liang, Zhe Long; Min, Jeong-Ki; Hong, Hyo Jeong; Kim, Jin-Man

    2011-10-01

    Gallbladder carcinoma is a lethal malignancy and is hard to cure by current treatment. Thus, identification of molecular prognostic markers to predict gallbladder carcinoma as therapeutic targets is urgently needed. Recent studies have demonstrated that L1 cell adhesion molecule is associated with the prognosis of variable malignancy. Here, we investigated L1 cell adhesion molecule expression in gallbladder carcinoma and its prognostic significance. In this study, we examined L1 cell adhesion molecule expression in tumor specimens from 69 patients with gallbladder carcinoma by immunohistochemistry and analyzed the correlation between L1 cell adhesion molecule expression and clinicopathologic factors or survival. L1 cell adhesion molecule was not expressed in the normal epithelium of the gallbladder but in 63.8% of gallbladder carcinomas, remarkably at the invasive front of the tumors. In addition, L1 cell adhesion molecule expression was significantly associated with high histologic grade, advanced pathologic T stage and clinical stage, and positive venous/lymphatic invasion. Multivariate analyses showed that L1 cell adhesion molecule expression (hazard ratio, 3.503; P = .028) and clinical stage (hazard ratio, 3.091; P = .042) were independent risk factor for disease-free survival. L1 cell adhesion molecule expression in gallbladder carcinoma was significantly correlated with tumor progression and unfavorable clinicopathologic features. L1 cell adhesion molecule expression was an independent poor prognostic factor for disease-free survival in patients with gallbladder carcinoma. Taken together, our findings suggest that L1 cell adhesion molecule expression could be used as a novel prognostic factor for patient survival and might be a potential therapeutic target in gallbladder carcinomas. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. 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

  7. Prognostic Significance of Preoperative Circulating Monocyte Count in Patients With Breast Cancer

    PubMed Central

    Wen, Jiahuai; Ye, Feng; Huang, Xiaojia; Li, Shuaijie; Yang, Lu; Xiao, Xiangsheng; Xie, Xiaoming

    2015-01-01

    Abstract Growing evidence showed that inflammation response plays an important role in cancer development and progression, and absolute lymphocyte count (ALC), absolute monocyte count (AMC), and lymphocyte to monocyte ratio (LMR) have been used as parameters of systemic inflammation in several tumors. In this study, we evaluated the prognostic significance of preoperative ALC, AMC and LMR in breast cancer and 2000 patients between January 2002 and December 2008 at Sun Yat-Sen University Cancer Center were enrolled. Patients were grouped by the cut-off value according to the receiver operating characteristics (ROC) curve analysis. Kaplan–Meier analysis showed that patients with elevated AMC levels (>0.48 × 109/L) had shorter overall survival (OS, P < 0.001). In multivariate analysis, preoperative AMC was identified as an independent prognostic parameter for OS in breast cancer patients (hazard ratio = 1.374, 95% confidence interval: 1.045–1.807). Subgroup analyses revealed that AMC was an unfavorable prognostic factor in stage II–III breast cancer patients and Luminal B, human epithelial growth factor receptor-2 overexpressing subtype, and triple-negative breast cancer (all P < 0.05). Additionally, the prognostic value of ALC and LMR could not be proven in the current study. Preoperative AMC may serve as an easily available and low-priced parameter to predict the outcomes of breast cancer. PMID:26656374

  8. Forkhead-box A1 (FOXA1) expression in breast cancer and its prognostic significance.

    PubMed

    Habashy, Hany Onsy; Powe, Desmond G; Rakha, Emad A; Ball, Graham; Paish, Claire; Gee, Julia; Nicholson, Robert I; Ellis, Ian O

    2008-07-01

    The forkhead-box A1 (FOXA1) controls downstream transcription of oestrogen receptor (ER)-regulated genes. In this study, the biological and prognostic value of FOXA1 expression was assessed immunohistochemically in a large and well-characterised series of invasive breast carcinoma with a long term follow-up using tissue microarray. FOXA1 expression was associated with steroid hormone receptors (ERalpha, PgR and AR), other variables of good prognosis such as smaller tumour size, lower histological grade, luminal cytokeratins (CK18 and CK7/8), BRCA1 and E-cadherin. Its expression showed an inverse relation with basal CKs (CK14 and CK5/6) and P-cadherin. We found an association between high FOXA1 expression and a better survival in the whole series however; multivariate analysis showed that FOXA1 was not an independent prognostic marker. In conclusion, our results show that FOXA1 protein is associated with markers of good prognosis supporting its role as a growth repressor in breast cancer. In this series, FOXA1 was found not to be of an independent prognostic significance in breast cancer and as such its immunohistochemical assessment alone does not appear to have relevance in routine practice to stratify ER-positive (luminal-like) tumours into clinically significant subgroups.

  9. Prognostic significance of clusterin expression in advanced-stage cervical cancer treated with curative intended radiotherapy.

    PubMed

    Watari, Hidemichi; Kinoshita, Rumiko; Han, Yimin; Wang, Lei; Hosaka, Masayoshi; Taguchi, Hiroshi; Tsuchiya, Kazuhiko; Tanaka, Shinya; Shirato, Hiroki; Sakuragi, Noriaki

    2012-03-01

    Overexpression of clusterin (CLU), an antiapoptotic molecule, has been reported to induce resistance to radiotherapy (RT) in a variety of cancer cell types. The aim of this study was to evaluate the significance of CLU expression to predict survival of patients with advanced-stage cervical cancer who received curative intended RT. Biopsy tissue specimens of advanced-stage cervical cancer before curative intended RT were obtained from 34 patients who were treated at Hokkaido University Hospital between 1998 and 2008 and whose complete medical records were available. The expression of CLU protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed using the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Clusterin protein was mainly present in the cytoplasm of cervical cancer cells. The expression of CLU protein in cervical cancer tissues before curative intended RT was not significantly related to any clinicopathological factors analyzed, including age, clinical stage, histologic type, and response to RT. Univariate analysis on prognostic factors showed that histologic type (P = 0.001), and CLU expression (P = 0.02) were related to survival. Multivariate analysis revealed that both histologic type (P = 0.002), and CLU expression (P = 0.02) were independent prognostic factors for overall survival. We conclude that CLU could be a new molecular marker to predict overall survival of patients with advanced-stage cervical cancer treated with curative intended RT.

  10. Clinical significance and prognostic value of Vav1 expression in Non-small cell lung cancer

    PubMed Central

    Qi, Yao; Kong, Fan-Ming; Deng, Qi; Li, Jing-Yi; Cui, Rui; Pu, Ye-Di; Zhai, Qiong-Li; Jia, Ying-Jie; Li, Yu-Ming

    2015-01-01

    Vav1 has been reported to be involved in human cancers, however, the expression and clinical significance of Vav1 in NSCLC are not fully understood. In the present study, we examined the expression of Vav1 in 170 NSCLC patients who underwent radical resection by the immunohistochemical analyses. The association between the Vav1 expression and clinicopathological variables was analyzed. The multivariate Cox proportional hazards model was conducted to determine the prognostic value of Vav1 on the long-term survival. The results showed that the elevated Vav1 expression was correlated positively with lymph node metastasis (P<0.001), T stage (P<0.001) and poor histological differentiation (P<0.001). Patients with negative or low Vav1 expression had better prognoses than those with high Vav1 expression (P<0.001). Multivariate analysis indicated that Vav1 was independent prognostic factor for overall survival (OS) (HR 2.079, 95% CI 1.564 to 2.762, P<0.001) and disease-free survival (DFS) (HR 1.810, 95% CI 1.391 to 2.356, P<0.001). Our findings showed that overexpressed Vav1 was correlated with aggressive tumor behavior. Val1 was an independent factor for NSCLC prognosis, which may serve as a novel prognostic factor and potential target to improve the long-term outcome of NSCLC. PMID:26396925

  11. 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

  12. Expression of hypoxic markers and their prognostic significance in soft tissue sarcoma

    PubMed Central

    KIM, JEUNG IL; CHOI, KYUNG UN; LEE, IN SOOK; CHOI, YOUNG JIN; KIM, WON TACK; SHIN, DONG HOON; KIM, KYUNGBIN; LEE, JEONG HEE; KIM, JEE YEON; SOL, MEE YOUNG

    2015-01-01

    Tumor hypoxia is significant in promoting tumor progression and resistance to therapy, and hypoxia-inducible factor 1α (HIF-1α) is essential in the adaptive response of cells to hypoxia. The aim of the present study was to investigate the expression of hypoxic markers and evaluate their prognostic significance in soft tissue sarcoma (STS). A retrospective analysis of 55 patients with STS from Pusan National University Hospital (Busan, Korea) between 1998 and 2007 was conducted, using immunohistochemistry to analyze the expression of HIF-1α, carbonic anhydrase 9 (CA9), glucose transporter-1 (GLUT1) and vascular endothelial growth factor (VEGF). The association between the overexpression of these markers and clinicopathological characteristics, including the overall survival (OS) and progression-free survival (PFS) in cases of STS, were investigated. Overexpression of HIF-1α, CA9, GLUT1 and VEGF was shown in 54.5, 32.7, 52.7 and 25.5% of tumors, respectively, and all exhibited a significant association with high French Federation of Cancer Centers (FNCLCC) grade and high American Joint Committee on Cancer (AJCC) stage. Overexpression of HIF-1α and CA9 was associated with a shorter OS and a shorter PFS. On multivariate analysis, AJCC stage and HIF-1α overexpression had independent prognostic significance. In the group receiving chemotherapy (n=27), HIF-1α overexpression was independently associated with a decreased OS. These results indicate that overexpression of HIF-1α and CA9 is associated with poor prognosis, and that HIF-1α overexpression is an independent unfavorable prognostic factor in STS. PMID:25789026

  13. The prognostic significance of UCA1 for predicting clinical outcome in patients with digestive system malignancies

    PubMed Central

    Zhu, Zheng-Ming

    2017-01-01

    Background Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers. Results The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52–2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45–2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30–3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer. Materials and methods A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified. Conclusions Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers. PMID:28380443

  14. The prognostic significance of UCA1 for predicting clinical outcome in patients with digestive system malignancies.

    PubMed

    Liu, Fang-Teng; Dong, Qing; Gao, Hui; Zhu, Zheng-Ming

    2017-06-20

    Urothelial Carcinoma Associated 1 (UCA1) was an originally identified lncRNA in bladder cancer. Previous studies have reported that UCA1 played a significant role in various types of cancer. This study aimed to clarify the prognostic value of UCA1 in digestive system cancers. The meta-analysis of 15 studies were included, comprising 1441 patients with digestive system cancers. The pooled results of 14 studies indicated that high expression of UCA1 was significantly associated with poorer OS in patients with digestive system cancers (HR: 1.89, 95 % CI: 1.52-2.26). In addition, UCA1 could be as an independent prognostic factor for predicting OS of patients (HR: 1.85, 95 % CI: 1.45-2.25). The pooled results of 3 studies indicated a significant association between UCA1 and DFS in patients with digestive system cancers (HR = 2.50; 95 % CI = 1.30-3.69). Statistical significance was also observed in subgroup meta-analysis. Furthermore, the clinicopathological values of UCA1 were discussed in esophageal cancer, colorectal cancer and pancreatic cancer. A comprehensive retrieval was performed to search studies evaluating the prognostic value of UCA1 in digestive system cancers. Many databases were involved, including PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure and Wanfang database. Quantitative meta-analysis was performed with standard statistical methods and the prognostic significance of UCA1 in digestive system cancers was qualified. Elevated level of UCA1 indicated the poor clinical outcome for patients with digestive system cancers. It may serve as a new biomarker related to prognosis in digestive system cancers.

  15. Prognostic significance of hemostatic parameters in patients with lung cancer.

    PubMed

    Unsal, Ebru; Atalay, Figen; Atikcan, Sükran; Yilmaz, Aydin

    2004-02-01

    There is a subclinical activation of coagulation and fibrinolysis system in lung cancer. Alterations in hemostatic system are seen frequently in lung cancer correlated with the prognosis of disease. In this prospective study, our purpose was to investigate the prognostic significance of hemostatic markers in patients with lung cancer. The study comprised 58 patients (22 squamous cell carcinoma, 16 adenocarcinoma, 20 small cell carcinoma). There were 55 men (95%)and 3 women (5%) with a mean age of 61 years range (36-74). Plasma level of platelets (PLT), prothrombin time (PT), active partial thromboplastin time (aPTT), antithrombin III (AT III), fibrinogen (F) and D-dimer level were measured before the initiation of any therapy. Patients were followed up for 17 (12-20) months. The median survival was determined as 6.4 months. Three histopathologic groups; squamous cell carcinoma, adenocarcinoma and small cell carcinoma were compared for the hemostatic parameters. There were no statistically significant differences among the histopathologic types for any of the parameters (P > 0.05). Patients were divided into two groups as patients without distant metastasis (stages I,II,III) and with distant metastasis (stage IV). The group with distant metastasis had higher level of D-dimer than the other group (P < 0.05). However, there were no statistically significant differences for D-dimer level between stages IIIB and IV (P > 0.05). Patients having high D-dimer and low AT III level had poor survival in our study. Thus, high level of D-dimer and low AT III level were determined as correlated with short survival (P < 0.05). These results suggest that elevated plasma level of D-dimer and low AT III level might be a sign of poor prognosis in patients with lung cancer.

  16. Sarcopenia: prevalence and prognostic significance in hospitalized patients.

    PubMed

    Gariballa, Salah; Alessa, Awad

    2013-10-01

    Sarcopenia is prevalent in older populations with many causes and varying outcomes however information for use in clinical practice is still lacking. The aim of this report is to identify the clinical determinants and prognostic significance of sarcopenia in a cohort of hospitalized acutely ill older patients. Four hundred and thirty two randomly selected patients had their baseline clinical characteristic data assessed within 72 h of admission, at 6 weeks and at 6 months. Nutritional status was assessed from anthropometric and biochemical data. Sarcopenia was diagnosed from low muscle mass and low muscle strength-hand grip using anthropometric measures based on the European Working Group criteria. Compared with patients without sarcopenia, those diagnosed with sarcopenia 44 (10%) were more likely to be older, have more depression symptoms and lower serum albumin concentration. The length of hospital stay (LOS) was significantly longer in patients diagnosed with sarcopenia compared with patients without sarcopenia [mean (SD) LOS 13.4 (8.8) versus 9.4 (7) days respectively, p = 0.003]. The risk of non-elective readmission in the 6 months follow up period was significantly lower in patients without sarcopenia compared with those diagnosed with sarcopenia (adjusted hazard ratio .53 (95% CI: .32 to .87, p = 0.013). The death rate was also lower in patients without sarcopenia 38/388 (10%), compared with those with sarcopenia 12/44 (27%), p-value = .001. Older people with sarcopenia have poor clinical outcome following acute illness compared with those without sarcopenia. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  17. Is tumor volume an independent prognostic factor in clinically localized prostate cancer?

    PubMed

    Kikuchi, Eiji; Scardino, Peter T; Wheeler, Thomas M; Slawin, Kevin M; Ohori, Makoto

    2004-08-01

    There continues to be debate regarding the prognostic significance of tumor volume (TV) in radical prostatectomy (RP) specimens. We assessed the prognostic significance of TV in a large series of patients followed for a long time to discover whether the effect of TV has changed with earlier detection of smaller tumors. TV was measured planimetrically in 1,302 consecutive RP specimens with clinical stage T1-3 prostate cancer from 1983 to 2000. We correlated TV with standard clinical and pathological features, and determined the prostate specific antigen nonprogression rate. Median followup was 46 months (range 1 to 202). TV was weakly associated with other clinical and pathological features. Median TV decreased significantly over time (2.16 cm3 before 1995 vs 1.25 cm3 after 1995, p <0.001) and this decrease was also found within each clinical stage. In univariate analysis TV correlated strongly with the probability of progression. However, in multivariate analysis TV was not a significant independent predictor of prognosis, either in the whole cohort of patients or in those with peripheral zone cancer only. Even in univariate analysis TV had no effect on prognosis for patients in whom cancer was either confined to the prostate or was Gleason score 2 through 6. TV provides no independent prognostic information when considered in multivariate analysis with Gleason score and pathological stage. Measurement of TV before treatment is less likely to characterize prostate cancer accurately than assessment of tumor grade and extent. There seems to be little reason to measure TV routinely in RP specimens.

  18. CHIP functions as a novel suppressor of tumour angiogenesis with prognostic significance in human gastric cancer.

    PubMed

    Wang, Shouyu; Wu, Xuming; Zhang, Jianbing; Chen, Yansu; Xu, Jin; Xia, Xiaowei; He, Song; Qiang, Fulin; Li, Aiping; Shu, Yongqian; Røe, Oluf Dimitri; Li, Gang; Zhou, Jianwei W

    2013-04-01

    CHIP (carboxy terminus of Hsc70 interacting protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several tumour related proteins, and acts as a suppressor of tumour metastasis. This study explored the biological function and clinical significance of CHIP in gastric cancer (GC). The prognostic value of CHIP expression was evaluated using tissue microarray and immunohistochemical staining in two independent human GC cohorts. The role of CHIP on tumorigenicity and angiogenesis was determined in vitro and in vivo. CHIP expression was significantly decreased in GC lesions compared with paired non-cancerous tissues. Low tumoral CHIP expression significantly correlated with clinicopathological characteristics in patients, as well as with shorter overall survival in both cohorts. Multivariate Cox regression analysis revealed that CHIP expression was an independent prognostic factor for human GC patients. Moreover, CHIP overexpression impeded the formation of anchorage independent colonies in soft agar, suppressed the growth of xenografts in nude mice and inhibited endothelial cell growth and tube formation by suppressing nuclear factor κB (NF-κB) mediated interleukin 8 (IL-8) expression in vitro. In vivo studies also confirmed that CHIP inhibited blood vessel formation and recruitment of CD31 positive cells in matrigel plugs. Also, CHIP interacted with NF-κB/p65 and promoted its ubiquitination and degradation by proteasome, terminating NF-κB activity and inhibiting IL-8-induced angiogenesis, which correlated with subsequent tumour metastasis. Decreased CHIP expression in GC resulted in increased angiogenesis and contributed to GC progression and poor prognosis. CHIP expression is a GC candidate clinical prognostic marker and a putative treatment target.

  19. Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer.

    PubMed

    Prat, Aleix; Cheang, Maggie Chon U; Martín, Miguel; Parker, Joel S; Carrasco, Eva; Caballero, Rosalía; Tyldesley, Scott; Gelmon, Karen; Bernard, Philip S; Nielsen, Torsten O; Perou, Charles M

    2013-01-10

    Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) -positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) -positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14

  20. Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer

    PubMed Central

    Aziz, Sura; Wik, Elisabeth; Davidsen, Benedicte; Aas, Hans; Aas, Turid; Akslen, Lars A.

    2017-01-01

    Presence of lymph node (LN) metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218), as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996–2009). Sections were reviewed for the largest metastatic tumor diameter (TD-MET), nodal afferent and efferent vascular invasion (AVI and EVI), extra-nodal extension (ENE), number of ENE foci, as well as circumferential (CD-ENE) and perpendicular (PD-ENE) diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT) diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS) or breast cancer specific survival (BCSS). Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value) in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively). To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer. PMID:28199370

  1. Prognostic significance of metallothionein expression in renal cell carcinoma

    PubMed Central

    Mitropoulos, Dionisios; Kyroudi-Voulgari, Aspasia; Theocharis, Stamatis; Serafetinides, Efraim; Moraitis, Epaminondas; Zervas, Anastasios; Kittas, Christos

    2005-01-01

    Background Metallothionein (MT) protein expression deficiency has been implicated in carcinogenesis while MT over expression in tumors is indicative of tumor resistance to anti-cancer treatment. The purpose of the study was to examine the expression of MT expression in human renal cell carcinoma (RCC) and to correlate MT positivity, the pattern and extent of MT expression with tumor histologic cell type and nuclear grade, pathologic stage and patients' survival. Patients and methods The immunohistochemical expression of MT was determined in 43 formalin-fixed and paraffin-embedded RCC specimens, using a mouse monoclonal antibody that reacts with both human MT-I and MT-II. Correlation was sought between immunohistochemical (MT positivity, intensity and extension of staining) and clinico-pathological data (histological cell type, tumor nuclear grade, pathologic stage and patients' survival). Results Positive MT staining was present in 21 cases (49%), being mild/moderate and intense in 8 and 13 cases, respectively. The pattern was cytoplasmic in 7 cases and was both cytoplasmic and nuclear in 14 cases. MT expression in a percentage of up to 25% of tumor cells (negative MT staining included) was observed in 31 cases, in a percentage 25–50% of tumor cells in 7 cases, and in a percentage of 50–75% of tumor cells in 5 cases. There was no significant correlation of MT intensity of staining to histological type, stage and patients' survival, while it was inversely correlated to higher tumor nuclear grade. MT extent of staining did not correlate with histological type, nuclear grade, and pathologic stage while a statistically significant association was found with patients' survival. Conclusions The inverse correlation between MT staining intensity and tumor nuclear grade in RCC suggests a role of MT in tumor differentiation process. Since extent of MT expression is inversely correlated with survival it may be possibly used as a clinical prognostic parameter. PMID

  2. Prognostic significance of small-artery structure in hypertension.

    PubMed

    Rizzoni, Damiano; Porteri, Enzo; Boari, Gianluca E M; De Ciuceis, Carolina; Sleiman, Intissar; Muiesan, Maria Lorenza; Castellano, Maurizio; Miclini, Marco; Agabiti-Rosei, Enrico

    2003-11-04

    The presence of structural alterations in the microcirculation may be considered an important mechanism of organ damage; however, it is not currently known whether structural alterations of small arteries may predict fatal and nonfatal cardiovascular events. One hundred twenty-eight patients were included in the present study. There were 59 patients with essential hypertension, 17 with pheochromocytoma, 20 with primary aldosteronism, 12 with renovascular hypertension, and 20 normotensive patients with non-insulin-dependent diabetes mellitus. All subjects were submitted to a biopsy of subcutaneous fat. Small resistance arteries were dissected and mounted on an isometric myograph, and the tunica media-to-internal lumen ratio (M/L) was measured. The subjects were reevaluated after an average follow-up time of 5.4 years. Thirty-seven subjects had a documented fatal or nonfatal cardiovascular event (5.32 events/100 patients per year). In the subcutaneous small arteries of subjects with cardiovascular events, a smaller internal diameter and a clearly greater M/L was observed. Our subjects were subdivided according to the presence of an M/L greater or smaller than the mean and median values observed in the whole population (0.098) or mean value +2 SD of our normal subjects (0.11). Life-table analyses showed a significant difference in event-free survival between the subgroups. Cox's proportional hazard model, considering all known cardiovascular risk factors, indicated that only pulse pressure (P=0.009) and M/L (P<0.0001) were significantly associated with the occurrence of cardiovascular events. Our results strongly indicate a relevant prognostic role of structural alterations in small resistance arteries of a high-risk population.

  3. HLA-DR expression in tumor epithelium is an independent prognostic indicator in esophageal adenocarcinoma patients.

    PubMed

    Dunne, Margaret R; Michielsen, Adriana J; O'Sullivan, Katie E; Cathcart, Mary Clare; Feighery, Ronan; Doyle, Brendan; Watson, Jenny A; O'Farrell, Naoimh J; Ravi, Narayanasamy; Kay, Elaine; Reynolds, John V; Ryan, Elizabeth J; O'Sullivan, Jacintha

    2017-07-01

    Esophageal adenocarcinoma (EAC) is an aggressive cancer with poor prognosis, and incidence is increasing rapidly in the Western world. Measurement of immune markers has been shown to have prognostic significance in a growing number of cancers, but whether this is true for EAC has yet to be evaluated. This study aimed to characterize HLA-DR expression in the esophagus across the inflammation to cancer progression sequence and to assess the prognostic significance of HLA-DR expression in EAC. Tissue microarrays (TMA) were constructed from esophageal tissue taken from patients at different stages in the cancer progression sequence; normal, esophagitis, Barrett's esophagus (BE), low- and high-grade dysplasia (LGD, HGD) and EAC. HLA-DR expression in tissue epithelium and stroma was assessed by immunohistochemistry. HLA-DR expression increased early in the inflammation to cancer progression sequence; with higher expression detected in esophagitis and BE compared to normal tissue. Patients with low (<50%) HLA-DR expression in the EAC tumor epithelium had significantly worse survival outcomes, compared to those with high expression, in both the tumor core (hazard ratio, HR = 2.178, p = 0.024, n = 70) and leading edge (HR = 2.86, p = 0.013, n = 41). Multivariate analysis demonstrated that low HLA-DR expression in leading edge tumor epithelium was an independent predictor of poor survival, associated with a 2.8-fold increase in disease-associated death (p = 0.023). This study shows that HLA-DR is an independent prognostic marker in EAC tumor epithelium. This may have implications for patient stratification strategies as well as EAC tumor immunology.

  4. Prognostic significance of human pituitary tumor-transforming gene immunohistochemical expression in differentiated thyroid cancer.

    PubMed

    Sáez, Carmen; Martínez-Brocca, M Asunción; Castilla, Carolina; Soto, Alfonso; Navarro, Elena; Tortolero, María; Pintor-Toro, José A; Japón, Miguel A

    2006-04-01

    Human securin pituitary tumor-transforming gene (hPTTG) is overexpressed in a variety of primary neoplasias, including differentiated thyroid cancer (DTC). The objective of this study was to examine the immunohistochemical expression of hPTTG in DTC and its association with known prognostic factors. hPTTG expression was analyzed by immunostaining on paraffin-embedded tissues. Clinical data were used to determine any associations between the expression of hPTTG and prognostic variables of DTC. A median follow-up of 43 months allowed us to analyze the persistence of disease and the response to radioiodine therapy. The study was conducted at a tertiary university hospital. Ninety-five patients undergoing surgical resection for DTC (n = 60) or benign nodular thyroid disease (n = 35) were studied. The main outcome measure was the association between hPTTG expression and prognostic factors in DTC. Among DTC cases, 21 (35%) had low and 39 (65%) had high hPTTG immunostaining. Adjacent nonneoplastic thyroid tissue was largely unstained. Among benign nodular thyroid disease cases, immunostaining was detected focally in eight (22.8%). A significant association was found between hPTTG expression and the presence of nodal (P < 0.01) or distant metastases (P < 0.05). A significant association with TNM was also found, because 83.3% of advanced TNM stages showed elevated hPTTG (P < 0.05). The association between hPTTG overexpression and decreased radioiodine uptake during follow-up was also significant (P < 0.05). The expression levels of hPTTG were confirmed as an independent prognostic factor for persistent disease (relative risk, 3.0; 95% confidence interval, 1.1-8.7; P < 0.05). Immunohistochemical analysis of hPTTG is of potential value in the determination of tumor aggressiveness in DTC.

  5. Serum total hCGβ level is an independent prognostic factor in transitional cell carcinoma of the urothelial tract

    PubMed Central

    Douglas, J; Sharp, A; Chau, C; Head, J; Drake, T; Wheater, M; Geldart, T; Mead, G; Crabb, S J

    2014-01-01

    Background: Serum total human chorionic gonadotrophin β subunit (hCGβ) level might have prognostic value in urothelial transitional cell carcinoma (TCC) but has not been investigated for independence from other prognostic variables. Methods: We utilised a clinical database of patients receiving chemotherapy between 2005 and 2011 for urothelial TCC and an independent cohort of radical cystectomy patients for validation purposes. Prognostic variables were tested by univariate Kaplan–Meier analyses and log-rank tests. Statistically significant variables were then assessed by multivariate Cox regression. Total hCGβ level was dichotomised at < vs ⩾2 IU l−1. Results: A total of 235 chemotherapy patients were eligible. For neoadjuvant chemotherapy, established prognostic factors including low ECOG performance status, normal haemoglobin, lower T stage and suitability for cisplatin-based chemotherapy were associated with favourable survival in univariate analyses. In addition, low hCGβ level was favourable when assessed either before (median survival not reached vs 1.86 years, P=0.001) or on completion of chemotherapy (4.27 vs 0.42 years, P=0.000002). This was confirmed in multivariate analyses and in patients receiving first- and second-line palliative chemotherapy, and in a radical cystectomy validation set. Conclusions: Serum total hCGβ level is an independent prognostic factor in patients receiving chemotherapy for urothelial TCC in both curative and palliative settings. PMID:24556622

  6. Clinical and prognostic significance of coagulation assays in melanoma.

    PubMed

    Tas, Faruk; Ciftci, Rumeysa; Kilic, Leyla; Bilgin, Elif; Keskin, Serkan; Sen, Fatma; Yildiz, Ibrahim; Yasasever, Vildan

    2012-10-01

    The activation of coagulation and fibrinolysis is frequently found among cancer patients. Such tumors are considered to be associated with a higher risk of invasion, metastases, and eventually worse outcome. The aim of this study is to explore the clinical and prognostic value of blood coagulation tests for melanoma patients. Pretreatment blood coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT), prothrombin activity (PTA), international normalized ratio (INR), D-dimer (DD), fibrinogen (F) levels, and platelet (PLT) counts were carried out. This prospective study included 61 melanoma patients [stage I-II (n=10), stage III (n=14), stage IV (n=37), M1c (n=26) disease], and 50 healthy controls. It included 34 (56%) men, median age 53 years, range 16-88 years. Over half of the patients (54%) were in the metastatic stage and most of them (70%) had M1c. The plasma level of pretreatment blood coagulation tests including DD, F, APTT, INR levels, and PLT counts showed a statistically significant difference between the patient and the control group (P<0.001 for all, but P=0.049 for INR). The levels of INR, DD, F, and PLT counts were higher and APTT was lower in the melanoma group, whereas the PT and PTA levels did not show any significant difference. There was a significant association between PT, PTA, INR, and PLT levels and the age of the patient. Patients with node metastasis in M0 disease had higher levels of PTA and PLT counts (P=0.002 and 0.048, respectively) and lower levels of PT and INR (P=0.056 and 0.046, respectively). The M1c patients tended to have higher plasma F levels (437 vs. 297 mg/dl, P=0.055) than M1a and M1b patients. The 1-year survival rate for all patients was 70%. In association with distant metastasis, advanced metastatic stage (M1c), elevated lactate dehydrogenase, and erythrocyte sedimentation rate, only elevated plasma F levels had a significantly adverse effect on survival among the coagulation

  7. Expression of FGFR1 is an independent prognostic factor in triple-negative breast cancer.

    PubMed

    Cheng, Chee Leong; Thike, Aye Aye; Tan, Sie Yong Jane; Chua, Pei Jou; Bay, Boon Huat; Tan, Puay Hoon

    2015-05-01

    Triple-negative breast cancers (TNBCs) are clinically aggressive tumors with limited treatment options. We examined the clinicopathological associations and prognostic implications of FGFR1 and FGFR2 expression in TNBCs. Tissue microarrays constructed from TNBCs were immunostained with FGFR1 and FGFR2, and scored by intensity and percentage of tumor cells stained per intensity for each subcellular compartment, which were correlated with clinicopathological parameters and survival. Cell migration following siRNA-mediated silencing of the FGFR1 gene in TNBC cell lines was also performed. 714 cases were informative for FGFR1 and FGFR2 immunostaining. Thresholds were defined as at least 1 % of cells stained and H-score of 100 or more. Proportions positive by each threshold were, respectively, 89.9 %, 7.1 % for FGFR1 (cytoplasm); 36.8 %, 7.8 % for FGFR2 (cytoplasm); and 33.5 %, 5.2 % for FGFR2 (membrane). Significant associations included FGFR1 and FGFR2 immunostaining for lobular subtype, FGFR2 immunostaining with lower grade, and more basal-like cancers with H-scores of 100 or more FGFR1 immunostaining. Multivariate Cox regression analysis showed FGFR1 expression in TNBCs to be independently prognostic for overall survival (OS) at both thresholds. Cases completely negative (less than 1 % staining) for FGFR1 immunostaining showed improved OS, while those with H-score of 100 or more immunostaining had the worst OS. Cell line studies revealed up-regulation of the FGFR1 gene in the MDA-MB-231 and Hs578T TNBC cells, and specific knockdown of FGFR1 expression significantly reduced cell migration in MDA-MB-231 cell line. In conclusion, FGFR1 expression in TNBCs is independently prognostic of OS, and H-score of 100 or more FGFR1 immunostaining may define tumors that have treatment potential via FGFR signaling inhibition.

  8. Prognostic Significance of Concurrent Hypovascular and Hypervascular Nodules in Patients with Hepatocellular Carcinoma

    PubMed Central

    Ogasawara, Sadahisa; Chiba, Tetsuhiro; Motoyama, Tenyu; Kanogawa, Naoya; Saito, Tomoko; Shinozaki, Yusuke; Suzuki, Eiichiro; Ooka, Yoshihiko; Tawada, Akinobu; Kato, Hideyuki; Okabe, Shinichiro; Kanai, Fumihiko; Yoshikawa, Masaharu; Yokosuka, Osamu

    2016-01-01

    Background Hypovascular nodules often occur together with hypervascular hepatocellular carcinoma (HCC). However, it remains controversial whether hypovascular nodules associated with hypervascular HCC have any prognostic value. This study evaluated the prognostic impact of hypovascular nodules co-existing with hypervascular HCC as diagnosed by computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), which can sensitively capture the dynamic changes in blood flow through the portal vein and hepatic artery in patients with early stage HCC. Methods A total of 152 patients with hypervascular HCC (≤ 30 mm, ≤ 3 nodules), who underwent initial local ablation, were analyzed retrospectively. All patients received CTAP and CTHA prior to treatment. Overall survival (OS) was compared among group A (hypervascular HCC only, 107 patients) and group B (hypovascular nodules and hypervascular HCC, 45 patients). Results Among all hypovascular nodules, 81% (46 of 57) developed hypervascularization within the follow-up period. The 1- and 2-year hypervascularization rates were 17% and 51%, respectively. OS was significantly longer for group A than for group B (P < 0.001). A Cox proportional-hazards model identified the presence of hypovascular nodules concurrent with hypervascular HCC as an independent poor prognostic factor. Conclusion The prognosis of hypervascular HCC patients with hypovascular nodules detected during CTAP and CTHA is poor. Clinical HCC categories seem to be dissimilar between patients with and without hypovascular nodules. PMID:27649084

  9. Expression and prognostic significance of zinc fingers and homeoboxes family members in renal cell carcinoma

    PubMed Central

    Jeong, Dae Cheon; Han, Myoung-Eun; Kim, Ji-Young; Liu, Liangwen; Jung, Jin-Sup; Oh, Sae-Ock

    2017-01-01

    Zinc fingers and homeoboxes (ZHX) is a transcription repressor family that contains three members; ZHX1, ZHX2, and ZHX3. Although ZHX family members have been associated with the progression of cancer, their values as prognostic factors in cancer patients have been poorly examined. Renal cell carcinoma (RCC) is a highly heterogeneous, aggressive cancer that responds variably to treatment. Thus, prognostic molecular markers are required to evaluate disease progression and to improve the survival. In clear cell RCC (ccRCC), ZHX1 and ZHX3 expression were found to be down-regulated but ZHX2 was up-regulated, and the expressions of ZHX1 and ZHX3 were significantly associated with pathological stage. Furthermore, Kaplan-Meier and multivariate regression analysis showed that reduction in the mRNA expression of ZHX1 was associated with poorer survival. Taken together, the present study shows loss of ZHX1 is correlated with ccRCC progression and suggests it is an independent prognostic marker in ccRCC. PMID:28152006

  10. Deletion of 8p is an independent prognostic parameter in prostate cancer

    PubMed Central

    Galal, Rami; Möller-Koop, Christina; Barrow, Phillipp; Tsourlakis, Maria Christina; Jacobsen, Frank; Hinsch, Andrea; Wittmer, Corinna; Steurer, Stefan; Krech, Till; Büscheck, Franziska; Clauditz, Till Sebastian; Beyer, Burkhard; Wilczak, Waldemar; Graefen, Markus; Huland, Hartwig; Minner, Sarah; Schlomm, Thorsten; Sauter, Guido; Simon, Ronald

    2017-01-01

    Deletion of chromosome 8p is the second most frequent genomic alteration in prostate cancer. To better understand its clinical significance, 8p deletion was analyzed by fluorescence in-situ hybridization on a prostate cancer tissue microarray. 8p deletion was found in 2,581 of 7,017 cancers (36.8%), and was linked to unfavorable tumor phenotype. 8p deletion increased from 29.5% in 4,456 pT2 and 47.8% in 1,598 pT3a to 53.0% in 931 pT3b-pT4 cancers (P < 0,0001). Deletions of 8p were detected in 25.5% of 1,653 Gleason ≤ 3 + 3, 36.6% of 3,880 Gleason 3 + 4, 50.2% of 1,090 Gleason 4 + 3, and 51.1% of 354 Gleason ≥ 4 + 4 tumors (P < 0,0001). 8p deletions were strongly linked to biochemical recurrence (P < 0.0001) independently from established pre- and postoperative prognostic factors (P = 0.0100). However, analysis of morphologically defined subgroups revealed, that 8p deletion lacked prognostic significance in subgroups with very good (Gleason ≤ 3 + 3, 3 + 4 with ≤ 5% Gleason 4) or very poor prognosis (pT3b, Gleason ≥ 8, pN1). 8p deletions were markedly more frequent in cancers with (53.5%) than without PTEN deletions (36.4%; P < 0,0001) and were slightly more frequent in ERG-positive (40.9%) than in ERG-negative cancers (34.7%, P < 0.0001) due to the association with the ERG-associated PTEN deletion. Cancers with 8p/PTEN co-deletions had a strikingly worse prognosis than cancers with deletion of PTEN or 8p alone (P ≤ 0.0003). In summary, 8p deletion is an independent prognostic parameter in prostate cancer that may act synergistically with PTEN deletions. Even statistically independent prognostic biomarkers like 8p may have limited clinical impact in morphologically well defined high or low risk cancers. PMID:27880722

  11. Prognostic significance of venous tumour thrombus consistency in patients with renal cell carcinoma (RCC).

    PubMed

    Weiss, Valerie L; Braun, Martin; Perner, Sven; Harz, Andreas; Vorreuther, Roland; Kristiansen, Glen; Müller, Stefan C; Ellinger, Jörg

    2014-02-01

    To identify the prognostic impact of venous tumour thrombus (VTT) in locally advanced renal cell carcinomas (RCCs). To further differentiate the clinical course of patients with VTT who have similar clinicopathological characteristics. We determined the VTT consistency (solid vs friable) in a retrospective cohort of 200 patients with RCC who had undergone nephrectomy between 1994 and 2011. We examined the correlation of VTT consistency in these patients with clinical and pathological variables. A total of 65% of the patients had solid VTT and 35% had friable VTT, which has a significantly lower amount of cell-cell adhesion molecules and connective tissue than solid VTT. We found that friable VTT was associated with advanced pT stage, higher VTT level, papillary RCC subtype and a lower age. Patients with friable VTT had a significantly shorter median overall survival than those with solid VTT (29 vs 89 months), but VTT consistency was not found to be an independent predictor of patients' survival in the multivariate Cox analysis. We found that VTT consistency was an independent significant predictor of overall survival in patients without evidence of distant and nodal metastases (N = 119). The VTT consistency is caused by the tumour and not by different surgical handling. Friable VTT is an important adverse prognostic predictor of overall survival in patients with non-metastatic RCC. © 2013 The Authors. BJU International © 2013 BJU International.

  12. Genome-wide profiling of papillary thyroid cancer identifies MUC1 as an independent prognostic marker.

    PubMed

    Wreesmann, Volkert B; Sieczka, Elizabeth M; Socci, Nicholas D; Hezel, Michael; Belbin, Thomas J; Childs, Geoffrey; Patel, Snehal G; Patel, Kepal N; Tallini, Giovanni; Prystowsky, Michael; Shaha, Ashok R; Kraus, Dennis; Shah, Jatin P; Rao, Pulivarthi H; Ghossein, Ronald; Singh, Bhuvanesh

    2004-06-01

    Clinicopathological variables used at present for prognostication and treatment selection for papillary thyroid carcinomas (PTCs) do not uniformly predict tumor behavior, necessitating identification of novel prognostic markers. Complicating the assessment is the long natural history of PTC and our rudimentary knowledge of its genetic composition. In this study we took advantage of differences in clinical behavior of two distinct variants of PTC, the aggressive tall-cell variant (TCV) and indolent conventional PTC (cPTC), to identify molecular prognosticators of outcome using complementary genome wide analyses. Comparative genome hybridization (CGH) and cDNA microarray (17,840 genes) analyses were used to detect changes in DNA copy number and gene expression in pathological cPTC and TCV. The findings from CGH and cDNA microarray analyses were correlated and validated by real-time PCR and immunohistochemical analyses on a series of 100 cases of cPTC and TCV. Genes identified by this approach were evaluated as prognostic markers in cPTC by immunohistochemistry on tissue arrays. CGH identified significant differences in the presence (76 versus 27%; P = 0.001) and type of DNA copy number aberrations in TCV compared with cPTC. Recurrent gains of 1p34-36, 1q21, 6p21-22, 9q34, 11q13, 17q25, 19, and 22 and losses of 2q21-31, 4, 5p14-q21, 6q11-22, 8q11-22, 9q11-32, and 13q21-31 were unique to TCV. Hierarchical clustering of gene expression profiles revealed significant overlap between TCV and cPTC, but further analysis identified 82 dysregulated genes differentially expressed among the PTC variants. Of these, MUC1 was of particular interest because amplification of 1q by CGH correlated with MUC1 amplification by real-time PCR analysis and protein overexpression by immunohistochemistry in TCV (P = 0.005). Multivariate analysis revealed a significant association between MUC1 overexpression and treatment outcome, independent of histopathological categorization (P = 0

  13. Alpha-methylacyl coenzyme A racemase overexpression in gallbladder carcinoma confers an independent prognostic indicator.

    PubMed

    Wu, Li-Ching; Chen, Li-Tzong; Tsai, Yueh-Ju; Lin, Chun-Mao; Lin, Ching-Yih; Tian, Yu-Fang; Sheu, Ming-Juen; Uen, Yih-Huei; Shiue, Yow-Ling; Wang, Yu-Hui; Yang, Shu-Jing; Wu, Wen-Ren; Li, Shau-Hsuan; Iwamuro, Masaya; Kobayasshi, Naoya; Huang, Hsuan-Ying; Li, Chien-Feng

    2012-04-01

    Increased β-oxidation of branched-chain fatty acids provides an additional metabolic advantage for cancer cells thereby enhancing tumour development and progression. Alpha-methylacyl coenzyme A racemase (AMACR) is an enzyme essential for the catabolism of branched-chain fatty acids that allows their subsequent β-oxidation and thus plays an important role in generating biological energy. However, the expression of AMACR has never been systemically investigated in gallbladder carcinoma. This study evaluated the expression status, associations with clinicopathological variables and prognostic implications of AMACR in a well-defined cohort of gallbladder carcinoma and confirmed their expression status in gallbladder carcinoma cells. AMACR immunostaining was assessable in 89 cases on tissue microarrays of gallbladder carcinoma, and it was correlated with clinicopathological factors and patient survival. In three gallbladder carcinoma cell lines and one non-tumorigenic cholangiocyte, AMACR mRNA expression was measured by real-time reverse transcription PCR and the endogenous expression of AMACR protein was analysed by western blotting. AMACR overexpression was significantly associated with an advanced primary tumour status (p=0.027) and American Joint Committee on Cancer stage (p=0.027), an increased histological grade (p=0.002) and vascular invasion (p=0.017). Importantly, AMACR overexpression independently predicted worse disease-specific survival (p=0.0452, RR 1.887). Expression levels of AMACR mRNA and total protein in various cells were comparable. The abundance of AMACR expression increased in tumour cells and was even higher in the metastatic cell line. In primary gallbladder carcinoma, AMACR overexpression was correlated with important prognosticators and independently portended worse outcomes, highlighting the potential prognostic and therapeutic utility of AMACR in gallbladder carcinoma.

  14. SERPINA4 is a novel independent prognostic indicator and a potential therapeutic target for colorectal cancer

    PubMed Central

    Sun, Hui-Min; Mi, Yu-Shuai; Yu, Fu-Dong; Han, Yang; Liu, Xi-Sheng; Lu, Su; Zhang, Yu; Zhao, Sen-Lin; Ye, Ling; Liu, Ting-Ting; Yang, Dao-Hua; Sun, Xiao-Feng; Qin, Xue-Bin; Zhou, Zong-Guang; Tang, Hua-Mei; Peng, Zhi-Hai

    2016-01-01

    Serpina family A member 4 (SERPINA4), also known as kallistatin, exerts important effects in inhibiting tumor growth and angiogenesis in many malignancies. However, the precise role of SERPINA4 in CRC has not been fully elucidated. The present study aimed to investigate the expression of SERPINA4 and its clinical significance in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses showed that the mRNA and protein expression of SERPINA4 in colorectal cancer (CRC) specimens was significantly decreased than that in adjacent normal mucosa. Immunohistochemistry (IHC) was conducted to characterize the expression pattern of SERPINA4 by using a tissue microarray (TMA) containing 327 archived paraffin-embedded CRC specimens. Statistical analyses revealed that decreased SERPINA4 expression was significantly associated with invasion depth, nodal involvement, distant metastasis, American Joint Committee on Cancer (AJCC) stage, and tumor differentiation. SERPINA4 was also an independent prognostic indicator of disease-free survival and overall survival in patients with CRC. Furthermore, the impact of altered SERPINA4 expression on CRC cells was analyzed with a series of in vitro and in vivo assays. The results demonstrated that SERPINA4 significantly inhibits malignant tumor progression and serves as a novel prognostic indicator and a potential therapeutic target for CRC. PMID:27648355

  15. Circulating Haptoglobin Is an Independent Prognostic Factor in the Sera of Patients with Epithelial Ovarian Cancer*

    PubMed Central

    Zhao, Changqing; Annamalai, Loganath; Guo, Changfa; Kothandaraman, Narasimhan; Koh, Stephen Chee Liang; Zhang, Huoming; Biswas, Arijit; Choolani, Mahesh

    2007-01-01

    Abstract OBJECTIVE This study was conducted to evaluate the prognostic significance of haptoglobin levels in the overall survival of patients presenting with various stages of epithelial ovarian cancer. MATERIALS AND METHODS We employed an in-house sandwich enzyme-linked immunosorbent assay method to determine the concentrations of preoperative haptoglobin and C-reactive protein (CRP) in sera samples obtained from 66 malignant tumors, 60 benign tumors, and 10 normal healthy women. RESULTS Levels of serum haptoglobin significantly correlated with tumor type (P < .001) and International Federation of Gynecology and Obstetrics stage (P < .05). A significant correlation was observed between clinical stage and patient survival (r = 5.99, P = .026). Our data also indicated that elevated serum haptoglobin levels were associated with poor outcome for overall survival using both univariate and multivariate analyses (P = .048 and P = .036 respectively). Using Pearson's correlation, we have noted that serum CRP concentrations significantly correlated with haptoglobin levels (r2 = 0.22, P < .001). Immunohistochemical findings and Western blot analyses were compatible with sera levels of haptoglobin in which a higher intensity of staining occurred in late-stage epithelial ovarian cancers. CONCLUSION This study provides evidence that preoperative serum levels of haptoglobin could serve as an independent prognostic factor in patients presenting with epithelial ovarian cancer. PMID:17325738

  16. 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

  17. Expression of cytoskeleton regulatory protein Mena in human hepatocellular carcinoma and its prognostic significance.

    PubMed

    Hu, Kunpeng; Wang, Jiani; Yao, Zhicheng; Liu, Bo; Lin, Yuan; Liu, Lei; Xu, Lihua

    2014-05-01

    The molecular mechanisms of the development and progression of hepatocellular carcinoma (HCC) are poorly understood. The main objective of this study was to analyze the expression of Enabled [mammalian Ena (Mena)] protein and its clinical significance in human HCC. The Mena expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction and Western blotting analysis in ten paired HCC tissues and the adjacent normal tissues. The expression of Mena protein in 81 specimens of HCC tissues was determined by immunohistochemistry. Associations of Mena expression with the clinicopathological features were analyzed, and prognosis of HCC patients was evaluated. The result shows the expression of Mena mRNA and protein was higher in HCC than in the adjacent normal tissues in ten paired samples. Mena was mainly accumulated in the cytoplasm of tumor cells and over-expressed in 40.74% (33/81) patients by immunohistochemical staining. Over-expression of Mena was significantly associated with poor cellular differentiation (P = 0.025), advanced tumor stage (P = 0.003) and worse disease-free survival (DFS, P < 0.001). In addition, Mena is an independent prognostic factor for DFS in multivariate analysis (HR 2.309, 95% CI 1.104-4.828; P = 0.026). Mena is up-regulated in HCC and associated with tumor differentiation and clinical stage. Mena may be an independent prognostic marker for DFS of HCC patients.

  18. Prognostic Significance of High Ki-67 Index and Histogenetic Subclassification in Primary Central Nervous System Lymphoma.

    PubMed

    Cho, Uiju; Oh, Woo Jin; Hong, Yong-Kil; Lee, Youn Soo

    2016-08-03

    In diffuse large B-cell lymphoma (DLBCL), the germinal center B-cell (GCB) subtype is associated with a better prognosis compared with the nongerminal center B-cell-like (non-GCB) subtype. However, validity of this immunohistochemical subgrouping in primary DLBCL of the central nervous system is unclear. A total 45 cases of primary central nervous system lymphoma (PCNS)/DLBCL were selected, and immunohistochemistries for CD10, Bcl-6, MUM1, and Ki-67 were performed. Each of the cases was subclassified as either GCB or non-GCB based on its immunoprofile. Among clinical and immunologic markers, patients under 70 years of age and who had methotrexate chemotherapy showed a significantly better overall survival (OS). High Ki-67 (ie, a Ki-67 index ≥90%) was an independent prognostic factor for a poor OS in the whole cohort and in the patients with non-GCB subtype tumors (P=0.017, HR=4.267, 95% CI, 1.3-14.0; P=0.031, HR=3.752, 95% CI, 1.3-12.5). Tumors were dominantly non-GCB subtype (41/45, 91.1%); only 4 (8.9%) were GCB subtype. The 2-year OS rates for these groups were 73% and 100%. There was, however, no statistically significant difference between these groups for OS and progression-free survival. The subclassification of PCNS/DLBCL into GCB and non-GCB subtypes did not seem to have a prognostic value. In non-GCB subtype PCNSL patients, high Ki-67 index was an adverse independent prognostic marker that could be used to stratify patients for more suitable management.

  19. Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

    PubMed Central

    Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

    2015-01-01

    To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging. PMID:25875542

  20. 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

  1. Plasma Level of Interleukin-35 as an Independent Prognostic Indicator in Hepatocellular Carcinoma.

    PubMed

    Qiu, Xiangting; Wang, Xinhua; Song, Yucui; Chen, Lingling

    2016-12-01

    Hepatocellular carcinoma is a major type of liver cancer with poor prognosis. The aim of the study was to determine the prognostic significance of plasma interleukin-35 level in hepatocellular carcinoma. A total of 153 hepatocellular carcinoma patients and 153 healthy controls were enrolled. Blood samples were obtained at admission. Plasma interleukin-35 level was analyzed by enzyme-linked immunosorbent assay. Distribution of T cell subset and expression of Fas/FasL protein were detected by flow cytometry. The patients were followed up for 2 years. Poor prognosis was defined as death of hepatocellular carcinoma. The plasma levels of interleukin-35 were significantly higher in the patients than the controls (25.1 ± 13.1, 9.3 ± 6.3 pg/mL, P < 0.001). After adjusted for multiple confounding factors, the multivariate logistic regression analyses reported that high level of interleukin-35 (≥25.0 pg/mL) was associated with the poor prognosis in the patients (OR 6.63, 95 % CI 3.27-13.47). Compared with the patients with low level of interleukin-35 (<25.0 pg/mL), the patients with high level of interleukin-35 showed higher frequencies of CD4+CD25+FoxP3+ and CD3+Foxp3+ regulatory T cells (P < 0.001 and P < 0.001) and also showed higher apoptosis levels of CD8+ T cells (P < 0.001). Circulating interleukin-35 concentration might be an independent prognostic indicator in hepatocellular carcinoma. Such prognostic significance could be partly involved in the activation of regulatory T cell and the apoptosis of CD8+ T cell.

  2. 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

  3. Prognostic Significance of Hyperglycemia in Patients with Brain Tumors: a Meta-Analysis.

    PubMed

    Liu, Hongwei; Liu, Zhixiong; Jiang, Bing; Ding, Xiping; Huo, Lei; Wan, Xin; Liu, Jinfang; Xia, Zhenyun

    2016-04-01

    Hyperglycemia has been associated with poor outcomes of patients with various diseases. There were several studies published to assess the association between hyperglycemia and prognosis of patients with brain tumors, but no consistent conclusion was available. We therefore performed a meta-analysis of available studies to evaluate the prognostic role of hyperglycemia in brain tumors. Several common databases were searched for eligible studies on the association between hyperglycemia and survival of patients with brain tumors. Two investigators used a set of predefined inclusion criteria to assess eligible studies independently. The pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the prognostic role of hyperglycemia. Finally, seven studies with a total of 2168 patients with brain tumors were included into the meta-analysis. Meta-analysis of total seven studies showed that hyperglycemia was significantly associated with shorter overall survival of brain tumors (HR = 2.04, 95% CI 1.51-2.76, P < 0.001). Meta-analysis of studies focusing on hyperglycemia showed that hyperglycemia was still significantly associated with shorter overall survival of brain tumors (HR = 1.82, 95% CI 1.29-2.59, P = 0.001). Meta-analysis of three studies on diabetes showed that diabetes was significantly associated with shorter overall survival of brain tumors (HR = 2.09, 95% CI 1.22-3.57, P = 0.007). Meta-regression analysis showed that there was no obvious difference in the roles of between hyperglycemia caused by glucocorticoids and hyperglycemia from diabetes (P = 0.25). Thus, hyperglycemia has an obvious prognostic significance in patients with brain tumors, and hyperglycemia is significantly associated with shorter overall survival of brain tumors.

  4. 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

  5. Epidermal growth factor receptor gene amplification and protein expression in glioblastoma multiforme: prognostic significance and relationship to other prognostic factors.

    PubMed

    Layfield, Lester J; Willmore, Carlynn; Tripp, Sheryl; Jones, Claudia; Jensen, Randy L

    2006-03-01

    Epidermal growth factor receptor (EGFR) overexpression occurs in a significant percentage of cases of glioblastoma multiforme (GBM), and amplification has been found in approximately 40% of these neoplasms. Controversy exists as to the prognostic significance of EGFR gene amplification: some reports have indicated that amplification is associated with a poor prognosis, while other authors have reported no relationship between gene amplification and prognosis. Some reports have found a poor prognosis to be associated with amplification of the EGFR gene in patients of all ages with GBM, while other authors have found EGFR amplification to be an independent predictor of prolonged survival in patients with GBM who are older than 60 years of age. The authors studied a series of 34 specimens (32 patients) with histologically proven GBM by immunohistochemistry for the presence of EGFR overexpression and by fluorescence in situ hybridization (FISH) for gene amplification of the EGFR gene. Results of these studies and data on patient age, sex, functional status, therapy, and survival were correlated to determine which variables were predictive of survival. p53 expression was also determined by immunohistochemistry and correlated with the other variables and survival.

  6. RECK is not an independent prognostic marker for breast cancer.

    PubMed

    Gomes, Luciana R; Fujita, André; Mott, Joni D; Soares, Fernando A; Labriola, Leticia; Sogayar, Mari C

    2015-10-08

    The REversion-inducing Cysteine-rich protein with Kazal motif (RECK) is a well-known inhibitor of matrix metalloproteinases (MMPs) and cellular invasion. Although high expression levels of RECK have already been correlated with a better clinical outcome for several tumor types, its main function, as well as its potential prognostic value for breast cancer patients, remain unclear. The RECK expression profile was investigated in a panel of human breast cell lines with distinct aggressiveness potential. RECK functional analysis was undertaken using RNA interference methodology. RECK protein levels were also analyzed in 1040 cases of breast cancer using immunohistochemistry and tissue microarrays (TMAs). The association between RECK expression and different clinico-pathological parameters, as well as the overall (OS) and disease-free (DFS) survival rates, were evaluated. Higher RECK protein expression levels were detected in more aggressive breast cancer cell lines (T4-2, MDA-MB-231 and Hs578T) than in non-invasive (MCF-7 and T47D) and non-tumorigenic (S1) cell lines. Indeed, silencing RECK in MDA-MB-231 cells resulted in elevated levels of pro-MMP-9 and increased invasion compared with scrambled (control) cells, without any effect on cell proliferation. Surprisingly, by RECK immunoreactivity analysis on TMAs, we found no association between RECK positivity and survival (OS and DFS) in breast cancer patients. Even considering the different tumor subtypes (luminal A, luminal B, Her2 type and basal-like) or lymph node status, RECK remained ineffective for predicting the disease outcome. Moreover, by multivariate Cox regression analysis, we found that RECK has no prognostic impact for OS and DFS, relative to standard clinical variables. Although it continues to serve as an invasion and MMP inhibitor in breast cancer, RECK expression analysis is not useful for prognosis of these patients.

  7. Prognostic significance of centromere 17 copy number gain in breast cancer depends on breast cancer subtype.

    PubMed

    Lee, Kyuongyul; Jang, Min Hye; Chung, Yul Ri; Lee, Yangkyu; Kang, Eunyoung; Kim, Sung-Won; Kim, Yu Jung; Kim, Jee Hyun; Kim, In Ah; Park, So Yeon

    2017-03-01

    Increased copy number of chromosome enumeration probe (CEP) targeting centromere 17 is frequently encountered during HER2 in situ hybridization (ISH) in breast cancer. The aim of this study was to clarify the clinicopathologic significance of CEP17 copy number gain in a relatively large series of breast cancer patients. We analyzed 945 cases of invasive breast cancers whose HER2 fluorescence ISH reports were available from 2004 to 2011 at a single institution and evaluated the association of CEP17 copy number gain with clinicopathologic features of tumors and patient survival. We detected 186 (19.7%) cases of CEP17 copy number gain (CEP17≥3.0) among 945 invasive breast cancers. In survival analysis, CEP17 copy number gain was not associated with disease-free survival of the patients in the whole group. Nonetheless, it was found to be an independent adverse prognostic factor in the HER2-negative group but not in the HER2-positive group. In further subgroup analyses, CEP17 copy number gain was revealed as an independent poor prognostic factor in HER2-negative and hormone receptor-positive breast cancers, and it was associated with aggressive histologic variables including high T stage, high histologic grade, lymphovascular invasion, p53 overexpression, and high Ki-67 proliferative index. In conclusion, we found that elevated CEP17 count can serve as a prognostic marker in luminal/HER2-negative subtype of invasive breast cancer. We advocate the use of the dual-colored fluorescence ISH using CEP17 rather than the single-colored one because it gives additional valuable information on CEP17 copy number alterations. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Prognostic significance of perigastric tumor deposits in patients with primary gastric cancer.

    PubMed

    Anup, Shrestha; Lu, Jun; Zheng, Chao-Hui; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Lin, Jian-Xian; Chen, Qi-Yue; Cao, Long-Long; Lin, Mi; Yu, Qian; Yang, Ying-Hong; Huang, Chang-Ming

    2017-07-19

    The presence and the prognostic significance of perigastric tumor deposits (TDs) in primary gastric cancer have not been extensively studied. The aim of this study was to evaluate the prognostic significance perigastric TDs in primary gastric cancer. From 2005 to 2010, 1250 patients underwent R0 gastrectomy at the Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China. Out of 1250 patients, 132 patients with perigastric TDs were identified. Additionally, 132 patients with staged matched gastric cancer without tumor deposits were selected as a control group. Perigastric TDs were observed in 132 (10.5%) of the 1250 patients with gastric cancer who underwent R0 gastrectomy. There were 94 males (71.21%) and 38 females (28.79%) (2.47:1). The mean age was 57.21 years. Clinicopathologic characteristics between the two groups matched well. There was a significant difference in the overall survival of those with and without TDs by univariate (p<0.05) and multivariate (p < 0.05) survival analysis. The 1-, 3-and 5-year overall survival rates of patients with TDswere69.6%, 39.3%, and 24.2%, respectively, and were significantly poorer than those of the staged matched control group. There was no correlation between the number of TDs and patient survival in patients with gastric cancer (p>0.05); however, when comparing each pT tumor group with the perigastric TD group, the stage T4 survival rate was very similar to that observed in patients with TDs. Perigastric TDs are an independent predictive prognostic factor for gastric cancer and may be appropriately considered a form of serosal invasion. We suggest that TDs should be included in TNM staging system for better outcomes.

  9. 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.

  10. MYC and MXI1 protein expression: potential prognostic significance in women with breast cancer in China.

    PubMed

    Xu, Lin-Ping; Sun, Yan; Li, Wei; Mai, Ling; Guo, Yong-Jun; Fan, Qing-Xia

    2014-01-01

    To investigate the expression levels and the clinical significance of MYC and MXI1 proteins in breast cancer. The expression levels of MYC and MXI1 were detected by immunohistochemical assay in 166 cases of breast cancer; the relationships among MYC, MXI1 and the clinicopathological parameters were analyzed by χ2 test. Univariate analysis and Cox's proportional hazards model were used to evaluate the prognostic significance of the 2 proteins. 27.71% of the tumor specimens showed high staining intensity for MYC (high-expression group, HEG-MYC) and 22.89% showed high staining intensity for MXI1 (HEG-MXI1); the expression of 2 proteins was negatively correlated (r = -0.177 p = 0.022). The Kaplan-Meier method for survival analysis showed that patients of the MYC-HEG demonstrated a significantly worse disease-specific survival than those of the MYC-low-expression group (LEG) (χ2 = 11.102, p = 0.001). However, patients of the MXI1-HEG had a significantly better disease-specific survival than those of the MXI1-LEG (χ2 = 7.858, p = 0.005). Both univariate analysis and Cox's proportional hazards model indicated that MYC and MXI1 could be independent prognostic molecular markers. MYC-HEG and MXI1-LEG levels are associated with poor prognosis in patients with breast cancer, suggesting that they may be useful molecular markers in breast cancer prognosis prediction.

  11. [Prognostic significance of the lung lesions in lymphogranulomatosis].

    PubMed

    Simbirtseva, L P; Gubareva, A V; Sheĭdakov, A A; Skripkina, N S

    1984-01-01

    Clinical, roentgenological and morphological data on 301 followed-up cases of Hodgkin's disease were analysed. The lung was involved in 99 patients (32.9%). Patients showing signs of intoxication, involvement of mediastinal, axillary and supraclavicular lymph nodes and prognostically unfavorable histologic patterns of lesion formed the group at high risk for lung affection. Five-year survival rate was 84.4% in the intact lung group, and 39.5%--in patients with diseased lung. As for cases of stage II and III with intact lung, the relevant figure was 86.0%--1.6 times that in cases of stage IIE-IIIE with lung lesions developing per continuitatem.

  12. [Prognostic significance of helical CT in patients with destructive pancreatitis].

    PubMed

    Bulanova, T V

    2000-01-01

    Spiral scanning computed tomography (CT) is able not only to image the pancreas and to evaluate its structure, but to interpret the status of the adjacent organs and tissues. CT symptoms of pancreatic necrotic changes and multiorgan failure were studied in the prospective follow-up of 47 patients with prior destructive pancreatitis (158 studies). CT differentially substantiated indications for choosing treatment policy for different forms of pancreatic lesions. The paper gives a quantitative assessment of necrotic pancreatic parencymatous areas and shows its prognostic value.

  13. 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.

  14. Prognostic significance of serum beta-2 microglobulin in patients with diffuse large B-cell lymphoma in the rituximab era

    PubMed Central

    Yoon, Shinkyo; Yoo, Changhoon; Park, Ji Hyun; Lee, Jung Bok; Park, Chan-sik; Huh, Jooryung; Lee, Yoonse; Kim, Kyung Won; Ryu, Jin-Sook; Kim, Seok Jin; Kim, Won Seog; Yoon, Dok Hyun; Suh, Cheolwon

    2016-01-01

    The prognostic value of serum beta-2 microglobulin for diffuse large B-cell lymphoma (DLBCL) is not well known in the rituximab era. A retrospective registry data analysis of 833 patients with de novo DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was conducted to establish the prognostic significance of serum beta-2 microglobulin at a ≥2.5 mg/L cutoff. Five-year progression-free survival (PFS, 76.1% vs. 41.0%; p < 0.001) and overall survival (OS, 83.8% vs. 49.2%; p < 0.001) were significantly worse in patients with elevated serum beta-2 microglobulin (n = 290, 34.8%). Furthermore, the five parameters of the International Prognostic Index, accompanying B symptoms, bone marrow involvement and impaired renal function were associated with worse PFS and OS. In multivariate analysis, elevated beta-2 microglobulin was a significant poor prognostic factor for PFS (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.29–2.24; p < 0.001) and OS (HR, 2.0; 95% CI, 1.47–2.75; p < 0.001). In an independent validation cohort of 258 R-CHOP treated patients with de novo DLBCL, elevated beta-2 microglobulin levels remained a significant poor prognostic factor for PFS (HR, 2.03; 95% CI, 1.23–3.32; p = 0.005) and exhibited a strong trend of association with worse OS (HR, 1.64; 95% CI, 0.98–2.75; p = 0.062). The significance of serum beta-2 microglobulin levels as an independent prognostic factor for patients with DLBCL receiving R-CHOP is confirmed. PMID:27764777

  15. Loss of 5-Hydroxymethylcytosine Is an Independent Unfavorable Prognostic Factor for Esophageal Squamous Cell Carcinoma

    PubMed Central

    Shi, Xuejiao; Yu, Yue; Luo, Mei; Zhang, Zhirong; Shi, Susheng; Feng, Xiaoli; Chen, Zhaoli; He, Jie

    2016-01-01

    Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine and 5-carboxylcytosine, which result in genomic DNA demethylation. It was reported that 5-hmC levels were decreased in a variety of cancers and could be regarded as an epigenetic hallmark of cancer. In the present study, 5-hmC levels were detected by immunohistochemistry (IHC) in 173 esophageal squamous cell carcinoma (ESCC) tissues and 91 corresponding adjacent non-tumor tissues; DNA dot blot assays were used to detect the 5-hmC level in another 50 pairs of ESCC tissues and adjacent non-tumor tissues. In addition, the mRNA level of TET1, TET2 and TET3 in these 50 pairs of ESCC tissues was detected by real-time PCR. The IHC and DNA dot blot results showed that 5-hmC levels were significantly lower in ESCC tissues compared with corresponding adjacent non-tumor tissues (P = 0.029). TET2 and TET3 expression was also significantly decreased in tumor tissues compared with paired non-tumor tissues (TET2, P < 0.0001; TET3, P = 0.009), and the decrease in 5-hmC was significantly associated with the downregulation of TET2 expression (r = 0.405, P = 0.004). Moreover, the loss of 5-hmC in ESCC tissues was significantly associated with poor overall survival among patients with ESCC (P = 0.043); multivariate Cox regression analysis showed that the loss of 5-hmC in ESCC tissues was an independent unfavorable prognostic indicator for patients with ESCC (HR = 1.569, P = 0.029). In conclusion, 5-hmC levels were decreased in ESCC tissues, and the loss of 5-hmC in tumor tissues was an independent unfavorable prognostic factor for patients with ESCC. PMID:27050164

  16. 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.

  17. Prognostic significance of the endoscopic ultrasound defined lymph node metastasis count in esophageal cancer.

    PubMed

    Twine, C P; Roberts, S A; Rawlinson, C E; Davies, L; Escofet, X; Dave, B V; Crosby, T D; Lewis, W G

    2010-11-01

    The key prognostic factor which predicts outcome after esophagectomy for cancer is the number of malignant lymph node metastases, but data regarding the accuracy of endoscopic ultrasound (EUS) in determining and predicting the metastatic lymph node count preoperatively are limited. The aim of this study was to assess the prognostic significance of EUS defined lymph node metastasis count (eLNMC) in patients diagnosed with esophageal cancer. Two hundred and sixty-seven consecutive patients (median age 63 years, 187 months) underwent specialist EUS followed by stage directed multidisciplinary treatment (183 esophagectomy [64 neoadjuvant chemotherapy, 19 neoadjuvant chemoradiotherapy], 79 definitive chemoradiotherapy, and 5 palliative therapy). The eLNMC was subdivided into four groups (0, 1, 2 to 4, >4) and the primary measure of outcome was survival. Survival was related to EUS tumor (T) stage (P < 0.0001), EUS node (N) stage (P < 0.0001), EUS tumor length (p < 0.0001), and eLNMC (P < 0.0001). Multivariable analysis revealed EUS tumor length (hazard ratio [HR] 1.071, 95% CI 1.008-1.138, P= 0.027) and eLNMC (HR 1.302, 95% CI 1.133-1.496, P= 0.0001) to be significantly and independently associated with survival. Median and 2-year survival for patients with 0, 1, 2-4, and >4 lymph node metastases were: 44 months and 71%, 36 months and 59%, 24 months and 50%, and 17 months and 32%, respectively. The total number of EUS defined lymph node metastases was an important and significant prognostic indicator. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

  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.

  19. Angiogenesis-Related Gene Expression Profile with Independent Prognostic Value in Advanced Ovarian Carcinoma

    PubMed Central

    Redondo, Andrés; Mariño-Enríquez, Adrián; Madero, Rosario; Espinosa, Enrique; Vara, Juan Ángel Fresno; Sánchez-Navarro, Iker; Hernández-Cortes, Ginés; Zamora, Pilar; Pérez-Fernández, Elia; Miguel-Martín, María; Suárez, Asunción; Palacios, José; González-Barón, Manuel; Hardisson, David

    2008-01-01

    Background Ovarian carcinoma is the most important cause of gynecological cancer-related mortality in Western societies. Despite the improved median overall survival in patients receiving chemotherapy regimens such as paclitaxel and carboplatin combination, relapse still occurs in most advanced diseased patients. Increased angiogenesis is associated with rapid recurrence and decreased survival in ovarian cancer. This study was planned to identify an angiogenesis-related gene expression profile with prognostic value in advanced ovarian carcinoma patients. Methodology/Principal Findings RNAs were collected from formalin-fixed paraffin-embedded samples of 61 patients with III/IV FIGO stage ovarian cancer who underwent surgical cytoreduction and received a carboplatin plus paclitaxel regimen. Expression levels of 82 angiogenesis related genes were measured by quantitative real-time polymerase chain reaction using TaqMan low-density arrays. A 34-gene-profile which was able to predict the overall survival of ovarian carcinoma patients was identified. After a leave-one-out cross validation, the profile distinguished two groups of patients with different outcomes. Median overall survival and progression-free survival for the high risk group was 28.3 and 15.0 months, respectively, and was not reached by patients in the low risk group at the end of follow-up. Moreover, the profile maintained an independent prognostic value in the multivariate analysis. The hazard ratio for death was 2.3 (95% CI, 1.5 to 3.2; p<0.001). Conclusions/Significance It is possible to generate a prognostic model for advanced ovarian carcinoma based on angiogenesis-related genes using formalin-fixed paraffin-embedded samples. The present results are consistent with the increasing weight of angiogenesis genes in the prognosis of ovarian carcinoma. PMID:19112514

  20. Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients

    PubMed Central

    Vincenzi, Bruno; Cremolini, Chiara; Sartore-Bianchi, Andrea; Russo, Antonio; Mannavola, Francesco; Perrone, Giuseppe; Pantano, Francesco; Loupakis, Fotios; Rossini, Daniele; Ongaro, Elena; Bonazzina, Erica; Dell'Aquila, Emanuela; Imperatori, Marco; Zoccoli, Alice; Bronte, Giuseppe; De Maglio, Giovanna; Fontanini, Gabriella; Natoli, Clara; Falcone, Alfredo; Santini, Daniele; Onetti-Muda, Andrea; Siena, Salvatore; Tonini, Giuseppe; Aprile, Giuseppe

    2015-01-01

    Introduction: Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/tumor sample, are available. We aimed to evaluate the prognostic value of K-Rasmutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. Patients and Methods: This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. Results: At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Discussion: Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set. PMID:26384309

  1. Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients.

    PubMed

    Vincenzi, Bruno; Cremolini, Chiara; Sartore-Bianchi, Andrea; Russo, Antonio; Mannavola, Francesco; Perrone, Giuseppe; Pantano, Francesco; Loupakis, Fotios; Rossini, Daniele; Ongaro, Elena; Bonazzina, Erica; Dell'Aquila, Emanuela; Imperatori, Marco; Zoccoli, Alice; Bronte, Giuseppe; De Maglio, Giovanna; Fontanini, Gabriella; Natoli, Clara; Falcone, Alfredo; Santini, Daniele; Onetti-Muda, Andrea; Siena, Salvatore; Tonini, Giuseppe; Aprile, Giuseppe

    2015-10-13

    Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/tumor sample, are available. We aimed to evaluate the prognostic value of K-Rasmutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set.

  2. Serum calcium is an independent prognostic factor of overall survival in Mexican patients with multiple myeloma.

    PubMed

    Maillet, Daniela; Montiel-Cervantes, Laura; Padilla-González, Ysabel; Sánchez-Cortés, Evelia; Xolotl-Castillo, Moisés; Vela-Ojed, Jorge; Reyes-Maldonado, Elba

    2012-01-01

    To evaluate the impact of different prognostic factors that has been suggested to be useful in predicting the survival of patients with multiple myeloma (MM). A longitudinal prospective study was conducted on 24 adult Mexican patients diagnosed with primary MM. The levels of expression of CD38, CD138 and cyclin D1 were analyzed in plasma cells (PCs) from patients and mononuclear cells from healthy donors. Serum levels of lactate dehydrogenase, creatinine, calcium, beta2 microglobulin and interleukin-6 (IL-6) as well as hemoglobin and platelet count were taken into consideration. RESULTS; CD138 and cyclin D1 levels in absolute numbers were significantly overexpressed in malignant PCs. A positive correlation was noted between cyclin D1 and CD38 expression levels in malignant PCs. IL-6 and serum calcium were also positively correlated in MM patients. Cyclin D1 overexpression was not associated with better overall survival (OS). Normal calcium levels were associated with better overall survival (OS). Serum calcium was the only variable correlating with better OS in Cox regression analysis. Serum calcium is an independent prognostic factor of OS in a population of Mexican patients with MM.

  3. Independent prognostic value of fascin immunoreactivity in stage III–IV colonic adenocarcinoma

    PubMed Central

    Puppa, G; Maisonneuve, P; Sonzogni, A; Masullo, M; Chiappa, A; Valerio, M; Zampino, M G; Franceschetti, I; Capelli, P; Chilosi, M; Menestrina, F; Viale, G; Pelosi, G

    2007-01-01

    Fascin, an actin-bundling protein involved in cell motility, has been shown to be upregulated in several types of carcinomas. In this study, we investigated the expression of fascin in 228 advanced colonic adenocarcinoma patients with a long follow-up. Fascin expression was compared with several clinicopathologic parameters and survival. Overall, fascin immunoreactivity was detected in 162 (71%) tumours with a prevalence for right-sided tumours (P<0.001). Fascin correlated significantly with sex, tumour grade and stage, mucinous differentiation, number of metastatic lymph nodes, extranodal tumour extension, and the occurrence of distant metastases. Patients with fascin-expressing tumours experienced a shorter disease-free and overall survival in comparison with those with negative tumours, and fascin immunoreactivity emerged as an independent prognostic factor in the multivariate analysis. Moreover, patients with the same tumour stages could be stratified in different risk categories for relapse and progression according to fascin expression. Our findings suggest that fascin is a useful prognostic marker for colonic adenocarcinomas. PMID:17375048

  4. [Prognostic significance of bicycle ergometry test in patients with myocarditis].

    PubMed

    Gavalova, R F; Borodina, V I

    1992-04-01

    A total of 42 patients with rheumatic carditis were examined in the acute-subacute period and following 3-5 years. Seventeen patients were diagnosed as having primary rheumatic carditis, 9 presented with tonsillogenic rheumatic carditis, and 16 had viral rheumatic carditis. The diagnosis of myocarditis was established on the basis of clinical, immunological, and virological findings. The study involved ECG, PhCG, PCG, and bicycle ergometer testing recordings. Groups of patients with good and poor prognosis were identified. Low threshold exercise, exercise-inadequate tachycardia, complex cardiac arrhythmias, phasic myocardial hypodynamic syndrome and volume exercise syndrome that are formed during performance are prognostically poor indicators. More profound electric and mechanic dysfunctions were observed in patients with tonsillogenic or viral myocarditis.

  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. Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancers: results of EVOCAPE 2 multicentre prospective study.

    PubMed

    Cotte, E; Peyrat, P; Piaton, E; Chapuis, F; Rivoire, M; Glehen, O; Arvieux, C; Mabrut, J-Y; Chipponi, J; Gilly, F-N

    2013-07-01

    In digestive cancers, the prognostic significance of intraperitoneal free cancer cells remains unclear (IPCC). The main objective of this study was to assess the prognostic significance of IPCC in colorectal and gastric adenocarcinoma. The secondary objectives were to evaluate the predictive significance of IPCC for the development of peritoneal carcinomatosis (PC) and to evaluate the prevalence of synchronous PC and IPCC. This was a prospective multicentre study. All patients undergoing surgery for a digestive tract cancer had peritoneal cytology taken. Patients with gastric and colorectal cancer with no residual tumour after surgery and no evidence of PC were followed-up for 2 years. The primary end point was overall survival. Between 2002 and 2007, 1364 patients were enrolled and 956 were followed-up over 2 years. Prevalence of IPCC was 5.7% in colon cancer, 0.6% in rectal cancer and 19.5% in gastric cancer. The overall 2-year survival rate for patients with IPCC was 34.7% versus 86.8% for patients with negative cytology (p<0.0001). By multivariate analysis, IPCC was not an independent prognostic factor. No relationship between cytology and recurrence was found. The presence of IPCC was not an independent prognostic and didn't add any additional prognostic information to the usual prognostic factors related to the tumour (pTNM and differentiation). Moreover the presence of IPCC detected with this method didn't appear to predict development of PC. Peritoneal cytology using conventional staining doesn't seem to be a useful tool for the staging of colorectal and gastric cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Loss of RhoGDI is a novel independent prognostic factor in hepatocellular carcinoma

    PubMed Central

    Li, Weidong; Wang, Hui; Jin, Xuejun; Zhao, Liang

    2013-01-01

    RhoGDI (Rho GDP-dissociation inhibitor alpha or RhoGDIα) has been identified as a regulator of Rho GTPases, which are essential for tumor progression, but its role in cancer remains controversial and little is known in hepatocellular carcinoma (HCC). Using immunohistochemistry, we analyzed RhoGDI expression in 147 clinicopathologically characterized HCC cases. RhoGDI expression was detected in cytoplasm of HCC tissues. Statistical analysis showed that there was no relationship between RhoGDI expression and clinicopathological features. Importantly, a significant trend was identified between loss of RhoGDI expression in HCC and worsening clinical prognosis. Multivariate survival analysis showed that negative RhoGDI expression was recognized as an independent prognostic factor of patient’s survival. Our results suggest that RhoGDI protein is a valuable marker of prognosis for patients with HCC. PMID:24228117

  8. BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received

    PubMed Central

    Dawson, S-J; Makretsov, N; Blows, F M; Driver, K E; Provenzano, E; Le Quesne, J; Baglietto, L; Severi, G; Giles, G G; McLean, C A; Callagy, G; Green, A R; Ellis, I; Gelmon, K; Turashvili, G; Leung, S; Aparicio, S; Huntsman, D; Caldas, C; Pharoah, P

    2010-01-01

    Background: Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL2), an antiapoptotic protein, has been proposed as a prognostic marker, but this effect is considered to relate to oestrogen receptor (ER) status. This study aimed to test the clinical validity of BCL2 as an independent prognostic marker. Methods: Five studies of 11 212 women with early-stage breast cancer were analysed. Individual patient data included tumour size, grade, lymph node status, endocrine therapy, chemotherapy and mortality. BCL2, ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) levels were determined in all tumours. A Cox model incorporating the time-dependent effects of each variable was used to explore the prognostic significance of BCL2. Results: In univariate analysis, ER, PR and BCL2 positivity was associated with improved survival and HER2 positivity with inferior survival. For ER and PR this effect was time dependent, whereas for BCL2 and HER2 the effect persisted over time. In multivariate analysis, BCL2 positivity retained independent prognostic significance (hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.66–0.88, P<0.001). BCL2 was a powerful prognostic marker in ER− (HR 0.63, 95% CI 0.54–0.74, P<0.001) and ER+ disease (HR 0.56, 95% CI 0.48–0.65, P<0.001), and in HER2− (HR 0.55, 95% CI 0.49–0.61, P<0.001) and HER2+ disease (HR 0.70, 95% CI 0.57–0.85, P<0.001), irrespective of the type of adjuvant therapy received. Addition of BCL2 to the Adjuvant! Online prognostic model, for a subset of cases with a 10-year follow-up, improved the survival prediction (P=0.0039). Conclusions: BCL2 is an independent indicator of favourable prognosis for all types of early-stage breast cancer. This study establishes the rationale for introduction of BCL2 immunohistochemistry to improve prognostic stratification. Further work

  9. Degree of Keratinization Is an Independent Prognostic Factor in Oral Squamous Cell Carcinoma.

    PubMed

    Wolfer, Susanne; Elstner, Stefan; Schultze-Mosgau, Stefan

    2017-06-30

    Keratinization is a routinely reported histologic feature in head and neck cancer. In contrast to numerous clinicopathologic parameters, the prognostic value of keratinization in oral squamous cell carcinoma (OSCC) is rarely reported in the literature. The purpose of this study was to review the outcome of patients with OSCC with a special focus on the degree of keratinization. In this retrospective cohort study, we evaluated the medical records at the Department of Oral and Maxillofacial Surgery, Jena University Hospital, and investigated the outcome of patients with OSCC with disease-free survival and disease-specific survival according to the degree of keratinization. This research also analyzed common clinical and histologic parameters such as age, gender, tumor site, T category, N category, resection margin, lymphovascular invasion, and extracapsular spread. Descriptive statistics were performed, and survival was calculated by the Kaplan-Meier method. Prognostic factors were analyzed by multivariate Cox analysis. In the sample of 151 OSCC patients, with a median age of 57.5 years and a male-female ratio of 4.03:1, 119 had tumors with no or low keratinization (K0 to K2) and 32 had tumors with good or high keratinization (K3 or K4). More recurrences were seen in patients with OSCC with low keratinization (P = .0008). The 5-year disease-free survival rate was significantly decreased for OSCC with low keratinization (52.9%) compared with good or high keratinization (93.2%) (P = .0008). The 5-year disease-specific survival rate was reduced to 66.1% (P = .0136) for patients with OSCC with low keratinization. Multivariate analysis showed that extracapsular spread (P = .001) and keratinization (P = .002) are independent, significant prognostic factors for recurrence in OSCC. Besides extracapsular spread, the degree of keratinization seems to be an important prognostic factor for recurrence and survival in OSCC. Our results indicate that the degree of

  10. Prognostic Significance of Progesterone Receptor–Positive Tumor Cells Within Immunohistochemically Defined Luminal A Breast Cancer

    PubMed Central

    Prat, Aleix; Cheang, Maggie Chon U.; Martín, Miguel; Parker, Joel S.; Carrasco, Eva; Caballero, Rosalía; Tyldesley, Scott; Gelmon, Karen; Bernard, Philip S.; Nielsen, Torsten O.; Perou, Charles M.

    2013-01-01

    Purpose Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Patients and Methods Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) –positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Results Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) –positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Conclusion Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A

  11. Almost all articles on cancer prognostic markers report statistically significant results.

    PubMed

    Kyzas, Panayiotis A; Denaxa-Kyza, Despina; Ioannidis, John P A

    2007-11-01

    We aimed to understand the extent of the pursuit for statistically significant results in the prognostic literature of cancer. We evaluated 340 articles included in prognostic marker meta-analyses (Database 1) and 1575 articles on cancer prognostic markers published in 2005 (Database 2). For each article, we examined whether the abstract reported any statistically significant prognostic effect for any marker and any outcome ('positive' articles). 'Negative' articles were further examined for statements made by the investigators to overcome the absence of prognostic statistical significance. We also examined how the articles of Database 1 had presented the relative risks that were included in the respective meta-analyses. 'Positive' prognostic articles comprised 90.6% and 95.8% in Databases 1 and 2, respectively. Most of the 'negative' prognostic articles claimed significance for other analyses, expanded on non-significant trends or offered apologies that were occasionally remote from the original study aims. Only five articles in Database 1 (1.5%) and 21 in Database 2 (1.3%) were fully 'negative' for all presented results in the abstract and without efforts to expand on non-significant trends or to defend the importance of the marker with other arguments. Of the statistically non-significant relative risks in the meta-analyses, 25% had been presented as statistically significant in the primary papers using different analyses compared with the respective meta-analysis. We conclude that almost all articles on cancer prognostic marker studies highlight some statistically significant results. Under strong reporting bias, statistical significance loses its discriminating ability for the importance of prognostic markers.

  12. 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

  13. 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

  14. Classification of microvascular patterns via cluster analysis reveals their prognostic significance in glioblastoma.

    PubMed

    Chen, Long; Lin, Zhi-Xiong; Lin, Guo-Shi; Zhou, Chang-Fu; Chen, Yu-Peng; Wang, Xing-Fu; Zheng, Zong-Qing

    2015-01-01

    There are limited researches focusing on microvascular patterns (MVPs) in human glioblastoma and their prognostic impact. We evaluated MVPs of 78 glioblastomas by CD34/periodic acid-Schiff dual staining and by cluster analysis of the percentage of microvascular area for distinct microvascular formations. The distribution of 5 types of basic microvascular formations, that is, microvascular sprouting (MS), vascular cluster (VC), vascular garland (VG), glomeruloid vascular proliferation (GVP), and vasculogenic mimicry (VM), was variable. Accordingly, cluster analysis classified MVPs into 2 types: type I MVP displayed prominent MSs and VCs, whereas type II MVP had numerous VGs, GVPs, and VMs. By analyzing the proportion of microvascular area for each type of formation, we determined that glioblastomas with few MSs and VCs had many GVPs and VMs, and vice versa. VG seemed to be a transitional type of formation. In case of type I MVP, expression of Ki-67 and p53 but not MGMT was significantly higher as compared with those of type II MVP (P < .05). Survival analysis showed that the type of MVPs presented as an independent prognostic factor of progression-free survival (PFS) and overall survival (OS) (both P < .001). Type II MVP had a more negative influence on PFS and OS than did type I MVP. We conclude that the heterogeneous MVPs in glioblastoma can be categorized properly by certain histopathologic and statistical analyses and may influence clinical outcome.

  15. The Significance of the Prognostic Nutritional Index for All Stages of Pancreatic Cancer.

    PubMed

    Lee, Sang Hoon; Chung, Moon Jae; Kim, Bun; Lee, Hee Seung; Lee, Hyun Jik; Heo, Ja Yoon; Kim, Yeong Jin; Park, Jeong Youp; Bang, Seungmin; Park, Seung Woo; Song, Si Young; Chung, Jae Bock

    2017-04-01

    Nutritional status affects the prognosis of various tumors. The prognostic nutritional index (PNI) is the known predictor of postoperative outcome in resectable pancreatic cancer patients. This study aimed to validate the prognostic value of PNI in all stages of pancreatic cancer. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed at Severance Hospital between January 2006 and December 2011. The PNI value was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (/mm(3)) at initial diagnosis. The median patient age was 62 yr, and 289 were men. The study group comprised resectable disease (n = 121), locally advanced disease (n = 118), and metastatic disease (n = 260). Univariate and multivariate analysis revealed that PNI ≤ 49.5 at initial diagnosis, together with performance status, platelet count, and clinical stage, was significantly associated with overall survival (hazard ratio, 1.562; all P < 0.05). Patients with PNI ≤ 49.5 (n = 208) had shorter median overall survival compared to patients with high PNI (9.8 vs. 14.2 mo; log rank, P < 0.001). In clinical stage subgroup analysis, initial PNI ≤49.5 independently predicted shorter overall survival, especially in resectable and metastatic disease (P = 0.041, P = 0.002, respectively).

  16. Prognostic significance of beta-2 adrenergic receptor in oral squamous cell carcinoma.

    PubMed

    Bravo-Calderón, Diego Mauricio; Oliveira, Denise Tostes; Marana, Aparecido Nilceu; Nonogaki, Suely; Carvalho, André Lopes; Kowalski, Luiz Paulo

    The aim of this study was to evaluate the expression of β2-adrenergic receptor (β2-AR) in oral squamous cell carcinoma (OSCC) and to investigate the correlations between expression level and clinical characteristics, outcome, and patient prognosis. A total of 106 OSCC patients underwent surgical treatment at the A.C. Camargo Cancer Hospital, São Paulo, Brazil, were analyzed for clinicopathological data, treatment, tumor outcome, prognosis and immunohistochemical expression of β2-AR. The β2-AR expression was statistically analyzed relative to clinicopathological variables and survival using the Chi-square test, Kaplan-Meier curves and Cox regression model. Most OSCC (72.6%) exhibited malignant cells with strong cytoplasmatic and membranous β2-AR expression. β2-AR expression was significantly associated with alcohol (p = 0.021), simultaneous consumption of alcohol and tobacco (p = 0.014) and T stage (p = 0.07). In addition, OSCC patients who exhibited strong β2-AR expression demonstrated a higher rate of overall survival (p = 0.001) and cancer specific survival (p = 0.004) compared to patients with weak/negative β2-AR expression. The Cox regression model demonstrated that strong β2-AR expression was an independent favorable prognostic factor for OSCC patients. These results suggest that the strong malignant cell β2-AR expression is a favorable prognostic factor for OSCC patients and could be used as a target for new anti-neoplastic pharmacological strategies.

  17. Epithelial cells in bone marrow of oesophageal cancer patients: a significant prognostic factor in multivariate analysis

    PubMed Central

    Thorban, S; Rosenberg, R; Busch, R; Roder, R J

    2000-01-01

    The detection of epithelial cells in bone marrow, blood or lymph nodes indicates a disseminatory potential of solid tumours. 225 patients with squamous cell carcinoma of the oesophagus were prospectively studied. Prior to any therapy, cytokeratin-positive (CK) cells in bone marrow were immunocytochemically detected in 75 patients with the monoclonal anti-epithelial-cell antibody A45-B/B3 and correlated with established histopathologic and patient-specific prognosis factors. The prognosis factors were assessed by multivariate analysis. Twenty-nine of 75 (38.7%) patients with oesophageal cancer showed CK-positive cells in bone marrow. The analyses of the mean and median overall survival time showed a significant difference between patients with and without epithelial cells in bone marrow (P< 0.001). Multivariate analysis in the total patient population and in patients with curative resection of the primary tumour confirmed the curative resection rate and the bone marrow status as the strongest independent prognostic factors, besides the T-category. The detection of epithelial cells in bone marrow of oesophageal cancer patients is a substantial prognostic factor proved by multivariate analysis and is helpful for exact preoperative staging, as well as monitoring of neoadjuvant therapy. © 2000 Cancer Research Campaign PMID:10883665

  18. Absence of FLICE-inhibitory protein is a novel independent prognostic marker for very short survival in pancreatic ductal adenocarcinoma.

    PubMed

    Schmid, Sandra J; Glatzel, Marie-Charlotte; Welke, Claudia; Kornmann, Marko; Kleger, Alexander; Barth, Thomas F E; Fulda, Simone; Lennerz, Jochen K; Möller, Peter

    2013-10-01

    Evading apoptosis is a hallmark of pancreatic cancer. In pancreatic cancer models, chemotherapy down-regulates the antiapoptotic protein cellular FLICE inhibitory protein (c-FLIP), which renders cells sensitive to apoptosis. Currently, the relevance of c-FLIP expression as a biomarker in pancreatic cancer is unknown, and here we assessed the prognostic significance of the c-FLIP expression status in a large cohort of pancreatic cancer patients with clinical follow-up. Cellular FLICE inhibitory protein expression levels were determined by immunohistochemistry in 120 surgically resected ductal pancreatic adenocarcinomas. Survival analysis by c-FLIP status was compared with established clinicopathologic biomarkers as well as Ki-67 and cyclooxygenase 2 expression levels as 2 other established independent prognostic biomarkers in pancreatic cancer. Of 120 tumors, 111 (91%) were c-FLIP positive, whereas 9 (9%) were completely c-FLIP negative. Cyclooxygenase 2 was positive in 59 cases (52%), and Ki-67 was positive in more than 10% of tumor cells in 51 cases (44%). Univariate and multivariate survival analysis (correcting for stage, grade, and proliferation index) showed that c-FLIP is an independent prognostic factor. Specifically, c-FLIP negativity identifies 9% of patients with a highly aggressive disease course (P = 0.0001). Cellular FLICE inhibitory protein expression status is a valuable prognostic biomarker in pancreatic cancer.

  19. Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.

    PubMed

    Wang, Dong-Yu; Done, Susan J; Mc Cready, David R; Leong, Wey L

    2014-07-04

    Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). The original training cohort reached a statistically significant difference (p < 0.05) in disease-free survivals between the three CMTC groups after an additional two years of follow-up (median = 55 months). The prognostic value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments.

  20. Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations

    PubMed Central

    2014-01-01

    Introduction Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. Methods An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). Results The original training cohort reached a statistically significant difference (p < 0.05) in disease-free survivals between the three CMTC groups after an additional two years of follow-up (median = 55 months). The prognostic value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Conclusions Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments. PMID

  1. Prognostic significance of MST1R dysregulation in renal cell tumors

    PubMed Central

    Pires-Luís, Ana S; Vieira-Coimbra, Márcia; Ferreira, Maria João; Ramalho-Carvalho, João; Costa-Pinheiro, Pedro; Antunes, Luís; Dias, Paula C; Lobo, Francisco; Oliveira, Jorge; Graça, Inês; Henrique, Rui; Jerónimo, Carmen

    2016-01-01

    Macrophage stimulating 1 receptor (MST1R) is a C-MET proto-oncogene family receptor tyrosine kinase. Promoter methylation patterns determine transcription of MST1R variants as hypermethylation of a region upstream of transcription start site (TSS) is associated with lack of MST1R long transcript (MST1R long) and expression of a short transcript with oncogenic potential. Thus, we aimed to investigate MST1R variant transcript regulation in renal cell tumors (RCT) and assess their prognostic potential. We found, in a series of 120 RCT comprising the four main subtypes (clear cell, papillary and chromophobe renal cell carcinoma, and oncocytoma), that higher methylation levels close to TSS were associated with total MST1R expression levels (MST1R total) in primary tumors (p=0.049) and renal cancer cell lines. After demethylating treatment, MST1R long/MST1R total ratio increased, as expected, in two renal cell carcinoma cell lines tested. However, in primary tumors with hypermethylation upstream of TSS, a decrease in MST1R long/MST1R total ratio was not detected, although higher expression ratio of nuclear factor-κB was apparent. Furthermore, survival analysis demonstrated that MST1R long/MST1R total ratio was independently associated with shorter disease-specific and disease-free survival, whereas MST1R total expression associated with shorter disease-specific survival. In conclusion, although promoter methylation patterns seem to determine MST1R global transcription regulation in renal cell carcinoma, other mechanisms might contribute to deregulate MST1R variant expression in RCT. Nevertheless, MST1R total expression and MST1R long/MST1R total ratio modulate the biological and clinical aggressiveness of renal cell carcinoma, as depicted by its prognostic significance, a finding that requires validation in a larger independent series. PMID:27648366

  2. 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.

  3. The prognostic value and pathobiological significance of Glasgow microenvironment score in gastric cancer.

    PubMed

    Zhou, Zhi-Hua; Ji, Cheng-Dong; Zhu, Jiang; Xiao, Hua-Liang; Zhao, Hai-Bin; Cui, You-Hong; Bian, Xiu-Wu

    2017-05-01

    To evaluate the prognostic value and pathobiological significance of Glasgow microenvironment score (GMS), a parameter based on tumor stroma percentage and inflammatory cell infiltration, in gastric cancer. A total of 225 cases of gastric cancer were histologically reviewed, and GMS was evaluated for each case. The association between GMS and patients' survival was investigated. Then the relationship between GMS and mismatch repair (MMR) status, Epstein-Barr virus (EBV) infection were determined using immunohistochemistry (IHC) and in situ hybridization, and the expression of PD1/PD-L1 was examined. Furthermore, the amount of cancer-associated fibroblasts (CAFs), the content and maturity of collagen components were detected using IHC, Picrosirius Red staining and second harmonic generation imaging. GMS was significantly associated with clinical outcomes of gastric cancer, and multivariate analysis indicated that GMS was an independent factor (HR 1.725, P = 0.002). Low GMS was a manifestation of better prognosis and inflammatory tumor microenvironment, which was related to MMR deficiency (P = 0.042) and EBV infection (P = 0.032), and within this microenvironment, expression of PD-L1 in carcinoma cells (P = 0.030) or in inflammatory cells (P = 0.029) was significantly higher. In contrast, high GMS linked to a poorer survival and desmoplastic stroma, in which there existed markedly increased CAFs and collagen deposition. GMS can serve as a useful prognostic factor for gastric cancer, and according to GMS, the tumor microenvironment in this cancer type may be partially classified as inflammatory or desmoplastic microenvironment that possesses different pathobiological features.

  4. Tumor budding is an independent prognostic factor for prediction of lymph node metastasis in oral squamous cell carcinoma.

    PubMed

    Angadi, Punnya V; Patil, Prakash V; Hallikeri, Kaveri; Mallapur, M D; Hallikerimath, Seema; Kale, Alka D

    2015-04-01

    Despite the enormous advances in diagnostic and management modalities of oral squamous cell carcinoma (OSCC), the mortality rates have remained stagnant with a 5-year survival rate of <50% challenging the available methods of prognostic assessment. Presence of tumor budding has been associated with aggressive behavior and is correlated with lymph node metastasis, recurrence, distant metastasis, and decreased survival in several cancers. However, the prognostic significance of this apparently simple to evaluate parameter is sparse in OSCC. A total of 75 cases of surgically excised OSCC were analyzed for tumor budding along with other clinicopathologic parameters. Tumor budding was graded as high and low intensity based on presence and absence of ≥10 or <10 budding foci in hematoxylin and eosin-stained sections. An association between the clinicopathological parameters, lymph node metastases with the budding index was examined using univariate and multivariate analyses. Tumor budding was evident in 89% of cases with around 45.3% of the cases demonstrated high-intensity budding. High-intensity tumor budding was significantly associated with lymph node metastasis and depth of invasion. Multivariate analysis demonstrated that tumor budding and depth of invasion were significant independent predictors for lymph node metastasis. Tumor budding is frequently encountered histologic marker in OSCC. High-intensity tumor budding is a strong independent prognostic factor for prediction of lymph node metastasis. © The Author(s) 2015.

  5. Prognostic significance of extranodal extension of regional lymph node metastasis in papillary thyroid cancer.

    PubMed

    Wu, Ming-Hsun; Shen, Wen T; Gosnell, Jessica; Duh, Quan-Yang

    2015-09-01

    and disease-free survival (DFS; p < .001) than those without extranodal extension. The prognosis of patients with stage 4a/4b cancer who had no extranodal extension was the same as patients with stage 3 cancer. The status of extranodal extension seems to be a stronger prognostic predictor than the location of metastatic lymph nodes (N1a/1b). Presence of extranodal extension of metastatic nodes is a significant adverse independent prognostic factor for patients with lymph node metastasis from papillary cancer. This may need to be considered in future updates of the TNM system for thyroid cancer. © 2014 Wiley Periodicals, Inc.

  6. 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

  7. Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma

    PubMed Central

    2012-01-01

    Background Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique. Methods Sixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model. Results Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression

  8. Immunological subtypes analysis of Uygur diffuse large B-cell lymphoma in Xinjiang and their prognostic significance.

    PubMed

    Jia, Cun-Dong; Liang, Li-Ping; Yang, Li-Li; Yue, Na; Zhao, Feng; Bai, Jing-Ping

    2015-01-01

    This study aims to explore the application of Choi's typing method in the immunological typing of diffuse large B-cell lymphoma (DLBCL) in Xinjiang Autonomous Region and its prognostic significance. Seventy-eight cases of DLBCL tumor tissues from Xinjiang were collected to detect the expression of germinal center B (GCB) cell-expressed transcript-1, FOXP1, CD10, bcl-6, and MUM1 using an immunohistochemical method. Then, immunological typing was carried out using Choi's typing method, and the survival analysis was performed using Kaplan-Meier method. Cox proportional hazard model was used to analyze the prognostic factors. GCB-cell-like-DLBCL and non-GCB-DLBCL accounting for 29.5% (23/78) and 70.5% (55/78), respectively. The 3-year overall survival of GCB-DLBCL was 58%, significantly higher than that of non-GCB-DLBCL (39%, P < 0.05). Multivariate analysis showed that International Prognostic Index and immunological typing were two independent prognostic factors for Uygur patients with DLBCL. Non-GCB-DLBCL is the main type of DLBCL in Xinjiang and Choi's typing method can be a helpful indicator to determine the prognosis of the Uygur DLBCL in Xinjiang.

  9. Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases

    PubMed Central

    Qian, Yun; Sang, Yiwen; Wang, Frederick X.C.; Hong, Bo; Wang, Qi; Zhou, Xinhui; Weng, Tianhao; Wu, Zhigang; Zheng, Min; Zhang, Hong; Yao, Hangping

    2016-01-01

    Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer. PMID:27750217

  10. Determinants and Prognostic Significance of Hematoma Sedimentation Levels in Acute Intracerebral Hemorrhage.

    PubMed

    Sato, Shoichiro; Delcourt, Candice; Zhang, Shihong; Arima, Hisatomi; Heeley, Emma; Zheng, Danni; Al-Shahi Salman, Rustam; Stapf, Christian; Tzourio, Christophe; Robinson, Thompson; Lindley, Richard I; Chalmers, John; Anderson, Craig S

    2016-01-01

    This study aimed at identifying the determinants and prognostic significance of a sedimentation level (fluid-blood level) in the hematoma among patients with acute intracerebral hemorrhage (ICH) who participated in the main Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Post-hoc analysis of the INTERACT2 dataset, a randomized controlled trial of patients with acute ICH with elevated systolic blood pressure (SBP), randomly assigned to intensive (target SBP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Patients with a sedimentation level at baseline assessment on CT, and modified Rankin Scale score at 90-day, were included in these analyses. Factors associated with a sedimentation level and its significance in relation to 90-day clinical outcomes were assessed in univariable and multivariable logistic regression models. Of 2,065 participants, 19 (1%) had sedimentation level on baseline CT, which was independently associated with warfarin use (p = 0.006) and lobar ICH (p = 0.025). Sedimentation level was also associated with death or major disability at 90-day in both crude (84 vs. 53%; p = 0.014) and multivariable analyses adjusted for age, gender, Chinese region, warfarin use, baseline National Institutes of Health Stroke Scale score, onset to CT time, volume and location of ICH, intraventricular extension, and randomized intensive BP lowering (OR 3.94, 95% CI 1.01-15.37; p = 0.049). The presence of hematoma sedimentation level on baseline CT is associated with warfarin use and lobar location of ICH, and predicts a worse outcome. Although uncommon, sedimentation level is an easily detectable prognostic factor in acute ICH. © 2015 S. Karger AG, Basel.

  11. Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes.

    PubMed

    Solé, Francesc; Luño, Elisa; Sanzo, Carmen; Espinet, Blanca; Sanz, Guillermo F; Cervera, José; Calasanz, María José; Cigudosa, Juan Cruz; Millà, Fuensanta; Ribera, Josep Maria; Bureo, Encarna; Marquez, Maria Luisa; Arranz, Eva; Florensa, Lourdes

    2005-09-01

    The main prognostic factors in myelodysplastic syndromes (MDS) are chromosomal abnormalities, the proportion of blasts in bone marrow and number and degree of cytopenias. A consensus-defined International Prognostic Scoring System (IPSS) for predicting outcome and planning therapy in MDS has been developed, but its prognostic value in a large and independent series remains unproven. Furthermore, the intermediate-risk cytogenetic subgroup defined by the IPSS includes a miscellaneous number of different single abnormalities of uncertain prognostic significance at present. The main aim of the present study was to identify chromosomal abnormalities with a previously unrecognized good or poor prognosis in order to find new cytogenetic markers with predictive value. We report the cytogenetic findings in a series of 968 patients with primary MDS from the Spanish Cytogenetics Working Group, Grupo Cooperativo Español de Citogenética Hematológica (GCECGH). In this series of 968 MDS patients, we found various cytogenetic aberrations with a new prognostic impact. Complex karyotype, -7/7q- and i(17q) had a poor prognosis; normal karyotype, loss of Y chromosome, deletion 11q, deletion 12p and deletion 20q as single alterations had a good prognosis. Intermediate prognosis aberrations were rearrangements of 3q21q26, trisomy 8, trisomy 9, translocations of 11q and del(17p). Finally, a new group of single or double cytogenetic abnormalities, most of which are considered rare cytogenetic events and are usually included in the intermediate category of the IPSS, showed a trend to poor prognosis. This study suggests that some specific chromosomal abnormalities could be segregated from the IPSS intermediate-risk cytogenetic prognostic subgroup and included in the low risk or in the poor risk groups.

  12. Interleukin 35 is an independent prognostic factor and a therapeutic target for nasopharyngeal carcinoma

    PubMed Central

    Zhang, Yongquan; Wu, Hui; Tan, Qindong; Xiang, Kai

    2015-01-01

    Aim of the study Interleukin (IL)-35 is composed of two subunits: Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35. Recently, overexpression of IL-35 has been found in several types of cancers. However, its clinical significance in nasopharyngeal carcinoma is still obscure. We have studied the clinical significance of IL-35 expression and its correlation with outcome of nasopharyngeal carcinoma patients. Material and methods Interleukin 35 expression was investigated in 80 nasopharyngeal carcinoma cases by immunohistochemistry. Moreover, Fisher's exact test, Kaplan-Meier plots, and Cox proportional hazards regression were utilized to analyse these results. Results In the present study, IL-35 is highly expressed in the majority of nasopharyngeal carcinoma samples. EBI3 and p35 immunoreactivity in nasopharyngeal carcinoma samples was 67.5% and 51.3%, respectively. Both EBI3 and p35 expressions were significantly associated with advancement of tumour stage. In addition, EBI3 expression was also correlated with lymph node metastasis. Further analysis showed that EBI3 or p35 staining indicated unfavourable prognosis (p < 0.05). Multivariate analysis suggested EBI3 was an independent prognostic predictor (p < 0.05). Conclusions Our results indicate for the first time that IL-35 is correlated with progression of nasopharyngeal carcinoma. Therefore, IL-35 may be a useful target for the treatment of nasopharyngeal carcinoma. PMID:26034389

  13. Prognostic value and clinical significance of halo naevi regarding vitiligo.

    PubMed

    van Geel, N; Vandenhaute, S; Speeckaert, R; Brochez, L; Mollet, I; De Cooman, L; Lambert, J

    2011-04-01

    Vitiligo and halo naevi can present together or separately. Whether they are different entities remains unclear. To assess the clinical significance of halo naevi, both with respect to the future development of vitiligo, and to the clinical profile and course of vitiligo. In total, 291 patients were included in this study: patients with only halo naevi (group 1; n=40), patients with generalized vitiligo without halo naevi (group 2; n=173) and patients with generalized vitiligo with halo naevi (group 3; n=78). Patients with only halo naevi (group 1) reported significantly less associated autoimmune disease (P=0·001), were less likely to have a family history of vitiligo (P=0·013) and were less likely to have presence of Koebner phenomenon (P<0·001) compared with patients with generalized vitiligo (groups 2+3). Multiple halo naevi (≥3) were significantly more frequently observed (P=0·002) in patients from group 1 compared with patients from group 3. In group 3, halo naevi were reported prior to the development of vitiligo in 61% (mean±SD time interval of 33·7±5·17months). No significant correlation was observed between the presence of halo naevi and the extent, activity or subtype of vitiligo. However, halo naevi in patients with vitiligo significantly reduced the risk for associated autoimmune diseases, and age at onset of vitiligo was significantly lower compared with patients with vitiligo without halo naevi (P<0·001). Our results support the hypothesis that halo naevi can represent a distinct condition. In a subset of patients, the occurrence of halo naevi may be an initiating factor in the pathogenesis of vitiligo. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

  14. Significance of preoperative prognostic nutrition index as prognostic predictors in patients with metastatic renal cell carcinoma with tyrosine kinase inhibitors as first-line target therapy.

    PubMed

    Cai, Wen; Zhong, Hai; Kong, Wen; Dong, Baijun; Chen, Yonghui; Zhou, Lixin; Xue, Wei; Huang, Yiran; Zhang, Jin; Huang, Jiwei

    2017-09-09

    Prognostic nutritional index (PNI) is a recognized indicator of both immune and nutritional status. It was firstly used as a preoperative prognostic indicator, and its role in the prognosis of patients with metastatic renal cell carcinoma (mRCC) has not yet been investigated in large-scale study. The purpose of this work was to investigate the prognostic role of pretreatment PNI in patients with mRCC with sorafenib or sunitinib as first-line targeted therapy. In this retrospective single-center research, the Kaplan-Meier method was used to estimate the progression-free survival (PFS) and overall survival (OS) of 178 mRCC patients who received first-line therapy of sorafenib or sunitinib. Log-rank test was used to compare the survival outcomes of patients with low pretreatment PNI (PNI < 51.62) and high pretreatment PNI (PNI ≥ 51.62), and Cox proportional hazard regression model was used to compare PFS and OS between these two groups. Prognostic accuracy was determined using Harrell concordance index. The overall median PFS and OS time for all 178 patients were 11 months (95% CI 9-12 months) and 24 months (95% CI 19-33 months), respectively. Patients with low pretreatment PNI both had significantly shorter median PFS (7 vs 19 months, P < 0.001) and OS (14 vs 50 months, P < 0.001) than those with high PNI. Multivariate analysis showed that pretreatment PNI was an independent predictor of OS (HR 1.658, 95% CI 1.040-2.614, P = 0.033) and an independent predictor of PFS as well (HR 1.842, 95% CI 1.226-2.766, P = 0.003). The model built by the addition of pretreatment PNI improved predictive accuracy of PFS and OS compared with the International Metastatic Renal Cell Carcinoma Database Consortium Model (Heng model) (c-index: 0.68 and 0.70). Comparing to NLR (neutrophil-to-lymphocyte ratio) (0.69 and 0.72), PNI might be a preciser factor to predict PFS and OS (0.71 and 0.73). Low pretreatment PNI could be a significant risk factor for mRCC patients who

  15. Prognostic significance of preoperative aspartate aminotransferase to neutrophil ratio index in patients with hepatocellular carcinoma after hepatic resection

    PubMed Central

    Guo, Zhiyong; Pang, Hui; Chen, Dubo; Wang, Xiaoping; Ju, Weiqiang; Wang, Dongping; He, Xiaoshun; Hua, Yunpeng; Peng, Baogang

    2016-01-01

    Objectives Various inflammation-based prognostic scores have been associated with poor survival in patients with hepatocellular carcinoma (HCC), and neutrophils display important roles. However, few studies have illuminated the relationship between preoperative aspartate aminotransferase (AST) to neutrophil ratio index (ANRI) and poor prognosis of HCC. We aimed to clarify the prognostic value of ANRI and evaluate the ability of different inflammation-based prognostic scores such as ANRI, AST to lymphocyte ratio index (ALRI), AST to platelet count ratio index (APRI), neutrophil-lymphocyte ratio index (NLR), and platelet-lymphocyte ratio index (PLR). Methods Data were collected retrospectively from 303 patients who underwent curative resection for HCC. Preoperative ANRI, ALRI, APRI, NLR, PLR and clinico-pathological variables were analyzed. Univariate, multivariate and Kaplan-Meier analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS). Results ANRI was correlated with presence of HBsAg, AST, presence of cirrhosis, tumor size, PVTT, cancer of the liver Italian program (CLIP) score, recurrence. Univariate analysis showed ANRI, ALRI, APRI, NLR, PLR were significantly associated with DFS and OS in HCC patients with curative resection. After multivariate analysis, ANRI was demonstrated to be superior to ALRI, APRI, NLR, PLR, which were independently correlated with DFS and OS. Survival analysis showed that preoperative ANRI > 7.8 predicted poor prognosis of patients with HCC after hepatectomy. preoperative ANRI also showed different prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of ANRI and NLR. Conclusions preoperative ANRI is an independent effective predictor of prognosis for patients with HCC, higher levels of ANRI predict poorer outcomes and the combining ANRI and NLR increases the prognostic accuracy of testing. PMID

  16. Prognostic significance of preoperative C-reactive protein: albumin ratio in patients with clear cell renal cell carcinoma

    PubMed Central

    Chen, Zhen; Shao, Yingjie; Fan, Min; Zhuang, Qianfeng; Wang, Kun; Cao, Wei; Xu, Xianlin; He, Xiaozhou

    2015-01-01

    We undertook a retrospective analysis to evaluate the C-reactive protein/albumin (CRP/Alb) ratio for its prognostic value in patients with clear cell renal cell carcinoma (CCRCC). The study comprised 406 CCRCC patients undergoing nephrectomy between 2003 and 2012 in our hospital. The correlations among the pretreatment CRP/Alb ratio, clinicopathological parameters, and overall survival (OS) were evaluated. An elevated CRP/Alb ratio was associated with older age at surgery (P=0.007), more advanced TNM stage (P<0.001), more presence of tumor necrosis (P<0.001) and lymphovascular invasion (P<0.001), lower concentration of hemoglobin (P<0.001) and calcium (P=0.005), and shorter OS (P<0.001). The multivariate analysis confirmed that the CRP/Alb ratio independently predicted the OS of patients with CCRCC (P<0.001), the Glasgow Prognostic Score (GPS) (P=0.001) and modified GPS (mGPS) (P=0.019) were independent prognostic factors also. At last, we evaluated the prognostic value of the CRP/Alb ratio compared with the similar inflammation-based prognostic scores GPS and mGPS using the area under the curve (AUC). Although the differences were not statistically significant, the AUC value of the CRP/Alb ratio (continuous, categorical) was higher compared with the GPS and mGPS, except that the AUC value for the CRP/Alb ratio (categorical) at 3 years was lower than that for the GPS. The CRP/Alb ratio could take the place of the GPS and mGPS in terms of predicting prognosis in CCRCC. PMID:26823819

  17. 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.

  18. Prognostic significance of survivin in resected gallbladder cancer.

    PubMed

    Nigam, Jaya; Chandra, Abhijit; Kazmi, Hasan Raza; Parmar, Devendra; Singh, Devendra; Gupta, Vishal

    2015-03-01

    Survivin, a novel inhibitor of apoptosis, plays a role in oncogenesis and has been correlated with poor prognosis. We investigated its expression in gallbladder tissues of control, cholelithiasis, and gallbladder cancer (GBC). Survivin expression was correlated with different clinicopathologic parameters including prognosis in patients with GBC. Gallbladder tissue samples were collected from GBC (n = 39), cholelithiasis (n = 30), and control (n = 25). Expression of survivin messenger RNA (mRNA) was evaluated by real time polymerase chain reaction. Protein quantification was done by enzyme-linked immunosorbent assay. Significantly higher expression of survivin mRNA was observed in GBC (2.9-fold) and cholelithiasis (1.85-fold) as compared with control (P < 0.0001). In GBC, increased survivin expression (mRNA and protein) was significantly associated with higher tumor stage (stage III versus stage II) (P < 0.0001) and poor tumor differentiation (poor and moderate versus well) (P < 0.0001). No significant correlation was observed with any of the other clinicopathologic factors studied. Increased expression of survivin was associated with shorter survival (median survival 11.5 mo versus 18 mo). Differential expression of survivin in GBC suggests its possible role in gallbladder carcinogenesis. Its overexpression is associated with poor prognosis. Assessment of survivin might be used to stratify GBC patients for optimal treatment modalities, including targeted therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Prognostic significance of autoimmunity during treatment of melanoma with interferon.

    PubMed

    Krauze, Michal T; Tarhini, Ahmad; Gogas, Helen; Kirkwood, John M

    2011-07-01

    Since the pivotal cooperative group trials in the 1980's-90's,, high-dose interferon (HDI) has been the standard of adjuvant therapy. Despite multiple other trials evaluating potential new therapies in melanoma, HDI remains the only FDA-approved therapy for stage IIB and III melanoma. Initial reports from the more recent phase III international trials of modifications of the original HDI regimen linked the appearance of autoimmunity with improved outcomes of disease. Trials of high-dose interleukin-2, many years earlier, reported anecdotal observations that were consistent with the hypothesis that autoimmunity and clinical benefit of immunotherapies of melanoma are linked with one another. The only prospectively conducted study examining the appearance of clinical and laboratory evidence of autoimmunity during HDI therapy was published by Gogas and colleagues, demonstrating statistically significant impact on relapse-free survival and overall survival. Retrospectively conducted studies of different intermediate dosage regimens of interferon (IFN) have not fully confirmed the linkage of serological evidence of autoimmunity and improved survival outcomes. With the emergence of new immunotherapies in treatment of melanoma, this review highlights the importance of autoimmunity for future applications in melanoma and reviews significant differences of past studies evaluating the appearance of autoimmunity during IFN therapy in high-risk melanoma.

  20. Clinicopathological and prognostic significance of aberrant Arpin expression in gastric cancer

    PubMed Central

    Li, Tao; Zheng, Hong-Mei; Deng, Nai-Mei; Jiang, Ying-Jian; Wang, Jiang; Zhang, Dian-Liang

    2017-01-01

    AIM To detect the expression of Arpin, and determine its correlation with clinicopathological characteristics and the prognosis of gastric cancer (GC) patients. METHODS A total of 176 GC patients were enrolled as study subjects and classified into groups according to different clinicopathological variables. GC mucosal tissues were obtained via surgery. Another 43 paraffin-embedded tissue blocks of normal gastric epithelium (> 5 cm away from the edge of the tumor) were included in the control group. Immunohistochemistry (IHC) for the Arpin and Arp3 proteins was performed on the formalin-fixed, paraffin-embedded GC tissues. Additionally, expression of the Arpin protein in 43 normal gastric tissues was also determined using IHC. RESULTS Expression of the Arpin protein in GC was lower than that in normal gastric mucosa (30.68% vs 60.47%, P < 0.001). A χ2 test of the 176 GC samples used for IHC showed that decreased Arpin expression was associated with advanced TNM stage (P < 0.01) and the presence or absence of lymph node metastasis (80.92% vs 35.56%, P < 0.001). Additionally, a significant correlation was observed between the expression of Arpin and the presence of the Arp2/3 complex in GC tissues (χ2 = 30.535, P < 0.001). Moreover, a multivariate Cox regression analysis revealed that Arpin expression [hazard ratio (HR) = 0.551, P = 0.029] and TNM stage (HR = 5.344, P = 0.001) were independent prognostic markers for overall survival of GC patients. Regarding the 3-year disease-free survival (DFS), the recurrence rate of GC patients with low Arpin expression levels (median DFS 19 mo) was higher than that in the high-Arpin-expression group (median DFS 34 mo, P = 0.022). CONCLUSION Low Arpin levels are associated with clinicopathological variables and a poor prognosis in GC patients. Arpin may be regarded as a potential prognostic indicator in GC. PMID:28293092

  1. The prognostic significance of HOTAIR for predicting clinical outcome in patients with digestive system tumors.

    PubMed

    Ma, Gaoxiang; Wang, Qiaoyan; Lv, Chunye; Qiang, Fulin; Hua, Qiuhan; Chu, Haiyan; Du, Mulong; Tong, Na; Jiang, Yejuan; Wang, Meilin; Zhang, Zhengdong; Wang, Jian; Gong, Weida

    2015-12-01

    Although some studies have assessed the prognostic value of HOTAIR in patients with digestive system tumors, the relationship between the HOTAIR and outcome of digestive system tumors remains unknown. The PubMed was searched to identify the eligible studies. Here, we performed a meta-analysis with 11 studies, including a total of 903 cases. Pooled hazard ratios (HRs) and 95 % confidence interval (CI) of HOTAIR for cancer survival were calculated. We found that the pooled HR elevated HOTAIR expression in tumor tissues was 2.36 (95 % CI 1.88-2.97) compared with patients with low HOTAIR expression. Moreover, subgroup analysis revealed that HOTAIR overexpression was also markedly associated with short survival for esophageal squamous cell carcinoma (HR 2.19, 95 % CI 1.62-2.94) and gastric cancer (HR 1.66, 95 % CI 1.02-2.68). In addition, up-regulated HOTAIR was significantly related to survival of digestive system cancer among the studies with more follow-up time (follow time ≥ 5 years) (HR 2.51, 95 % CI 1.99-3.17). When stratified by HR resource and number of patients, the result indicated consistent results with the overall analysis. Subgroup analysis on ethnicities did not change the prognostic influence of elevated HOTAIR expression. Additionally, we conducted an independent validation cohort including 71 gastric cancer cases, in which patients with up-regulated HOTAIR expression had an unfavorable outcome with HR of 2.10 (95 % CI 1.10-4.03). The results suggest that aberrant HOTAIR expression may serve as a candidate positive marker to predict the prognosis of patients with carcinoma of digestive system.

  2. Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer.

    PubMed

    Abduljabbar, Rezvan; Al-Kaabi, Methaq Mueen; Negm, Ola H; Jerjees, Dena; Muftah, Abir A; Mukherjee, Abhik; Lai, Chun F; Buluwela, Laki; Ali, Simak; Tighe, Patrick J; Green, Andrew; Ellis, Ian; Rakha, Emad

    2015-04-01

    Peroxisome proliferator-activated receptor-gamma (PPARγ) is an adopted orphan receptor that belongs to the nuclear receptor superfamily of transcription factors. PPARγ is regarded as a differentiation factor and it plays an important role in regulating adipogenesis, cell growth, proliferation and tumour progression. In breast cancer (BC), PPARγ agonists were reported to inhibit proliferation and growth invasion and promote phenotypic changes associated with a less malignant and more differentiated status. This study aims to assess the prognostic and biological roles of PPARγ protein expression in a large cohort of BC patients (n = 1100) with emphasis on the luminal oestrogen receptor (ER) positive class. Immunohistochemistry was used to assess the levels of PPARγ expression in BC series prepared as tissue microarrays (TMAs). PPARγ antibody specificity was confirmed using Western blotting. PPARγ nuclear expression was detected in 79 % of the cases and its expression was positively correlated with the hormonal receptors (ER, progesterone receptor and androgen receptor). PPARγ levels were significantly higher in tumours with lobular subtype, smaller size and lower grade, while HER2-positive, ductal or medullary tumours were associated with lower PPARγ levels. Survival analysis showed that PPARγ is associated with better outcome in the whole series as well as in luminal ER-positive class. Cox regression model showed that PPARγ is an independent predictor of outcome. Higher PPARγ was associated with longer survival in patients with ER-positive tumours who did not receive hormone therapy. PPARγ is a good prognostic marker associated with hormone receptors. In patients with luminal BCs, PPARγ is a marker of better prognosis and is associated with longer survival.

  3. Overexpression of EGFR as an Independent Prognostic Factor in Adenocarcinoma of the Esophagogastric Junction.

    PubMed

    Aratani, Kenichi; Komatsu, Shuhei; Ichikawa, Daisuke; Ohashi, Takuma; Miyamae, Mahito; Okajima, Wataru; Imamura, Taisuke; Kiuchi, Jun; Nishibeppu, Keiji; Kosuga, Toshiyuki; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Okamoto, Kazuma; Tsuda, Hitoshi; Otsuji, Eigo

    2017-06-01

    Adenocarcinoma of the esophagogastric junction (AEG) has increased in Western and Eastern countries, and its prognosis remains poor. We tested whether epidermal growth factor receptor (EGFR), that is overexpressed in various tumors, acts as a cancer-promoting gene through overexpression in AEG. We analyzed 104 primary AEG tumors which were curatively resected in our hospital between 2000 and 2010. Overexpression of EGFR protein was detected in 47% primary AEG tumor samples, and significantly associated with venous and lymphatic invasion, tumor depth and lymph node metastasis. The high-expression group had a significantly poorer prognosis than the low expression group for overall and disease-free survival. EGFR positivity was independently associated with a worse outcome in the multivariate analysis (p=0.0397, hazard ratio(HR)=2.048). EGFR plays a pivotal role in AEG through its overexpression, which highlights its usefulness as a prognosticator and potential therapeutic target in AEG. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Mixed Carcinoma as an Independent Prognostic Factor in Submucosal Invasive Gastric Carcinoma.

    PubMed

    Park, Hyung Kyu; Lee, Kyung-Yung; Yoo, Moon-Won; Hwang, Tae Sook; Han, Hye Seung

    2016-06-01

    Mixed carcinoma shows a mixture of glandular and signet ring/poorly cohesive cellular histological components and the prognostic significance of each component is not fully understood. This study aimed to investigate the significance of the poorly cohesive cellular histological component as a risk factor for lymph node metastasis and to examine the diagnostic reliability of endoscopic biopsy. Clinicopathologic characteristics of 202 patients who underwent submucosal invasive gastric carcinoma resection with lymph node dissection in 2005-2012 were reviewed. Mixed carcinoma accounted for 27.2% (56/202) of cases. The overall prevalence of lymph node metastasis was 17.3% (35/202). Lymphatic invasion (P < 0.001), family history of carcinoma (P = 0.025), tumor size (P = 0.004), Lauren classification (P = 0.042), and presence of any poorly cohesive cellular histological component (P = 0.021) positively correlated with the lymph node metastasis rate on univariate analysis. Multivariate analyses revealed lymphatic invasion, family history of any carcinoma, and the presence of any poorly cohesive cellular histological component to be significant and independent factors related to lymph node metastasis. Review of preoperative biopsy slides showed that preoperative biopsy demonstrated a sensitivity of 63.6% and a specificity of 100% in detecting the presence of the poorly cohesive cellular histological component, compared with gastrectomy specimens. The presence of any poorly cohesive cellular histological component was an independent risk factor associated with lymph node metastasis in submucosal invasive gastric carcinoma. Endoscopic biopsy had limited value in predicting the presence and proportion of the poorly cohesive cellular histologic component due to the heterogeneity of mixed carcinoma.

  5. Clinical determinants and prognostic significance of the electrocardiographic strain pattern in chronic kidney disease patients.

    PubMed

    Cordeiro, Antonio C; Moraes, Aline A I; Cerutti, Virginia; França, Faustino; Quiroga, Borja; Amodeo, Celso; Picotti, Juliano C; Dutra, Lucas V; Rodrigues, Gabriel D; Amparo, Fernanda C; Lindholm, Bengt; Carrero, Juan Jesús

    2014-05-01

    The electrocardiographic (ECG) strain pattern (Strain) is a marker of left ventricular hypertrophy (LVH) severity that provides additional prognostic information beyond echocardiography (ECHO) in the community level. We sought to evaluate its clinical determinants and prognostic usefulness in chronic kidney disease (CKD) patients. We evaluated 284 non-dialysis-dependent patients with CKD stages 3 to 5 (mean age, 61 years [interquartile range, 53-67 years]; 62% men). Patients were followed for 23 months (range, 13-32 months) for cardiovascular (CV) events and/or death. Strain patients (n = 37; 13%) were using more antihypertensive drugs, had higher prevalence of peripheral vascular disease and smoking, and higher levels of C-reactive protein, cardiac troponin, and brain natriuretic peptide (BNP). The independent predictors of Strain were: left ventricular mass index (LVMI), BNP, and smoking. During follow-up, there were 44 cardiovascular events (fatal and non-fatal) and 22 non-CV deaths; and Strain was associated with a worse prognosis independently of LVMI. Adding Strain to a prognostic model of LVMI improved in 15% the risk discrimination for the composite endpoint and in 12% for the CV events. Strain associates with CV risk factors and adds prognostic information over and above that of ECHO-assessed LVMI. Its routine screening may allow early identification of high risk CKD patients.

  6. [Prognostic factors for inability to walk independently in patients with multiple system atrophy].

    PubMed

    Wang, Z W; Wu, X H; Qiu, F; Liu, J G; Yao, W; Jiang, M; Wang, S S; Chen, Z G; Qi, X K

    2017-02-01

    Objective: To explore the prognostic factors for inability to walk independently in patients with multiple system atrophy (MSA). Methods: A total of 123 patients with clinically confirmed MSA admitted to Navy General Hospital and Dongfang Hospital affiliated to the Second Clinical Medical College of Beijing University of Chinese Medicine, from February 2013 to February 2016, were retrospectively reviewed. Clinical data and all records were collected and all subjects were followed up by a telephone call in February 2016. The second milestone of activities of daily living scale (ADL), defined as inability to walk independently, was taken as the primary outcome. Eight possible prognostic factors were investigated and the survival analysis was performed with Cox proportional hazards model regression. Results: Of all the MSA patients, 74 subjects were men and 49 were women with a sex radio of 1.51∶1(M∶F). Seventy cases were diagnosed with MSA-cerebellar type (MSA-C) and 53 with MSA-Parkinson type (MSA-P) (C∶P=1.32∶1). Mean age at the onset of first symptom was (53±8) years old. All patients had severe autonomic nervous dysfunction. At the last follow-up, 56 cases (45.5%) were unable to walk independently. The median survival time from the onset of MSA to inability to walk independently was 73 months. The age of onset ≥ 55 years (HR=1.969, 95%CI 1.095-3.542, P=0.024) and the interval time from disease onset to combined motor and autonomic involvement≤3 years (HR=2.308, 95%CI 1.158-4.600, P=0.017) were independent prognostic factors for inability to walk independently, while gender, MSA clinical subtypes, initial symptoms, alcohol intake, smoking and toxic exposure were not indicators for independent walking (P>0.05). Conclusions: The prognostic factors for inability to walk independently in patients with MSA are the age of onset ≥55 years and the interval time from disease onset to combined motor and autonomic involvement≤3 years. Although factors

  7. The prognostic significance of iliac vessel calcification in renal transplantation.

    PubMed

    Aitken, E; Ramjug, S; Buist, L; Kingsmore, D

    2012-12-01

    vascular complications. Nineteen (86.4%) had moderate-severe vascular calcification on imaging. Four of the patients with vascular complications (18.2%) underwent transplantation (2 had below knee amputation (BKA) prior to transplantation; 1 developed distal ischemia on the same side as the transplantation 2 years postoperatively; 1 had bilateral above knee amputation (AKA) approximately 2 years after transplantation). Eleven (50%) of the patients with vascular complications were dead at 5 years of follow-up. Mortality and amputation rates were higher in patients with moderate-severe calcification than minimal calcification (30.1% vs 16.6%; P = .02 and 10.9% vs 1.8%; P = .003, respectively). There was no difference in rates of delayed graft function (DGF), biopsy-proven acute rejection (BPAR), or creatinine at 1 year between patients who underwent transplantation with moderate-severe calcification and those without, however, intraoperative vascular complications (26.7% vs 3%; P < .001), graft loss (28.1% vs 3.4%; P = .01), and death with a functioning transplant (9.7% vs 1.6%; P = .04) rates were higher in patients with extensive calcification compared with those without. Plain x-ray of the pelvis is a useful screening tool to identify those patients who may require further detailed vascular imaging prior to transplantation. Amputation rates following renal transplantation are low and peripheral vascular disease (PVD) in isolation should not preclude transplantation. Nevertheless, significant vascular calcification is predictive of mortality both with and without transplantation and graft loss in patients with a renal transplant. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Prognostic significance of intraoperative peritoneal washing cytology for patients with potentially resectable pancreatic ductal adenocarcinoma.

    PubMed

    Hoshimoto, Sojun; Hishinuma, Shoichi; Shirakawa, Hirofumi; Tomikawa, Moriaki; Ozawa, Iwao; Hoshi, Nobuo; Hoshi, Sayuri; Hirabayashi, Kaoru; Ogata, Yoshiro

    The prognostic significance of intraoperative peritoneal washing cytology (IPWC) in pancreatic ductal adenocarcinoma (PDAC) remains controversial, and the treatment strategy for PDAC patients with positive cytology has not been established. The objective of this study was to evaluate the clinical significance of IPWC in PDAC patients. This study included a retrospective cohort of 166 patients with curatively resected PDAC who underwent IPWC. Overall, 17 patients (10%) had positive cytology (CY+), and 149 (90%) patients were negative (CY-). Tumor location in the pancreatic body and/or tail and pancreatic anterior capsular invasion were independent predictors of a CY+ status (P = 0.012 and 0.041, respectively). The initial recurrence occurred at the peritoneum with a significantly higher frequency in CY+ patients (50%) than in CY- patients (12%) (P = 0.003). The median overall survival (OS) for CY+ patients was 12 months. The OS rates at 1 and 3 years were significantly higher for CY- patients (75.1% and 35.3%, respectively) versus CY+ patients (47.1% and 17.6%, respectively; P = 0.012). However, one CY+ patient survived for 66 months, and another two CY+ patients have survived for more than three years after surgery without evidence of peritoneal recurrence. In the multivariate analysis, the independent predictors of OS were a CY+ status, lymph node metastasis, and adjuvant chemotherapy. This study demonstrates that positive IPWC predicts early peritoneal recurrence and a poor prognosis for PDAC patients. However, a small but not insignificant subset of CY+ patients with PDAC may avoid peritoneal carcinomatosis. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  9. 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

  10. Free/Total Serum Prostate-Specific Antigen Ratio in Women with Colorectal Cancer Has Prognostic Significance.

    PubMed

    Duraker, Nüvit; Çaynak, Zeynep Civelek; Trabulus, Didem Can

    2017-03-01

    The presence of prostate-specific antigen (PSA) in colon cancer tissues has been shown, but its clinical significance has not been known yet in colorectal cancer patients. We investigated the prognostic significance of percent free PSA value (free PSA/total PSA × 100) in female patients with colorectal cancer. The serum concentrations of total and free PSA were measured by solid-phase two-site immunoradiometric assay in 184 patients. The cancer-specific survival (CSS) of patients with percent free PSA value ≥35 was significantly better compared to that of patients with percent free PSA value <35 (CSS rate was 82.9 and 55.5 %, respectively; log-rank x(2) = 8135, p = 0.004). In multivariate Cox analysis, this percent free PSA threshold value had independent prognostic significance (relative risk 0.27, 95 % confidence interval 0.11-0.64, p = 0.003). Percent free PSA value, calculated by serum total and free PSA levels, has prognostic significance in women with colorectal cancer. The studies with larger patient series, utilizing ultrasensitive PSA assays whose lowest detection limit is lower, are required for a clearer understanding of this issue.

  11. Monokine induced by interferon gamma (MIG/CXCL9) is an independent prognostic factor in newly diagnosed myeloma.

    PubMed

    Bolomsky, Arnold; Schreder, Martin; Hübl, Wolfgang; Zojer, Niklas; Hilbe, Wolfgang; Ludwig, Heinz

    2016-11-01

    Immune suppression is a hallmark of multiple myeloma (MM), but data on soluble factors involved in the fate of immune effector cells are limited. The CXCR3-binding chemokine monokine induced by interferon-gamma (MIG/CXCL9) has been associated with tumor progression, immune escape, and angiogenesis in several malignancies. We here aimed to evaluate the prognostic relevance of MIG in MM. MIG serum levels were significantly elevated in newly diagnosed MM patients (n = 105) compared to patients with monoclonal gammopathy of undetermined significance (MGUS; n = 17) and healthy controls (n = 37). MIG expression in stromal compartments but not purified MM cells correlated with serum levels. High MIG serum levels were significantly associated with established prognostic markers (international staging system: R = 0.25, p = 0.001; age: R = 0.47, p < 0.0001; lactate-dehydrogenase: R = 0.34, p = 0.0005) and poor overall survival (OS) (median OS 17.0 months vs. not reached, p < 0.001). A similar association was found for CXCL10 and CXCL11. Multivariate regression analysis indicated MIG as an independent prognostic factor of OS.

  12. Overexpression of YWHAZ as an independent prognostic factor in adenocarcinoma of the esophago-gastric junction

    PubMed Central

    Watanabe, Nobuyuki; Komatsu, Shuhei; Ichikawa, Daisuke; Miyamae, Mahito; Ohashi, Takuma; Okajima, Wataru; Kosuga, Toshiyuki; Konishi, Hirotaka; Shiozaki, Atsushi; Fujiwara, Hitoshi; Okamoto, Kazuma; Tsuda, Hitoshi; Otsuji, Eigo

    2016-01-01

    Several studies have demonstrated that YWHAZ (14-3-3ζ), included in the 14-3-3 family of proteins, is implicated in the initiation and progression of cancers. To detect a novel treatment target for adenocarcinoma of the esophagogastric junction (AEG), we tested whether YWHAZ acted as a cancer-promoting gene through its overexpression in AEG. We analyzed YWHAZ protein expression in 92 consecutive primary AEG tumors, which had been curatively resected in our institution between 2000 and 2010. Overexpression of the YWHAZ protein was frequently detected in primary AEG tumor samples (46% (42/92)). Overexpression of YWHAZ was significantly correlated with Siewert type III tumor, larger tumor size (≥40 mm) and higher rates of lymph node metastasis and recurrence. Patients with YWHAZ-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors (P = 0.011, log-rank test) in an intensity expression-dependent manner. Patients with YWHAZ-overexpression tumors had worse overall survival rates than those with lower-expression tumors. YWHAZ positivity was independently associated with a worse outcome in the multivariate analysis (P = 0.0015, hazard ratio 4.49 [1.736-13.06]). In conclusion, YWHAZ plays a crucial role in poor outcomes of patients with AEG through its overexpression, which highlights its usefulness as a prognosticator and potential therapeutic target and indicator in AEG. PMID:27904785

  13. 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

  14. History of tuberculosis as an independent prognostic factor for lung cancer survival.

    PubMed

    Heuvers, Marlies E; Aerts, Joachim G J V; Hegmans, Joost P; Veltman, Joris D; Uitterlinden, André G; Ruiter, Rikje; Rodenburg, Eline M; Hofman, Albert; Bakker, Marleen; Hoogsteden, Henk C; Stricker, Bruno H; van Klaveren, Rob J

    2012-06-01

    It is well known that pulmonary tuberculosis is associated with an increased risk of lung cancer. We investigated whether a history of pulmonary tuberculosis is an independent risk factor for lung cancer survival in Caucasian patients. The data of the prospective population-based cohort of The Rotterdam Study were used. During a mean follow-up time of 18 years, there were 214 incident cases of pathology-proven lung cancer in a source population of 7983 study participants. History of tuberculosis was assessed at baseline by interviewers using standardized questionnaires. Associations of lung cancer survival with the occurrence of pulmonary tuberculosis were assessed using Cox's proportional hazard regression analysis adjusted for age, gender, pack-years, educational level and tumor stage. A history of tuberculosis was reported in 13 of the 214 subjects with lung cancer. The survival of patients with lung cancer was significantly shorter in subjects with a history of pulmonary tuberculosis (HR=2.36, CI95%: 1.1-4.9), than in subjects without a history of pulmonary tuberculosis with a mean difference of 311 days. The presence of a history of pulmonary tuberculosis may be an important prognostic factor in the survival of lung cancer. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. 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

  16. Evaluation of diagnostic and prognostic significance of Ki-67 index in pulmonary carcinoid tumours.

    PubMed

    Clay, V; Papaxoinis, G; Sanderson, B; Valle, J W; Howell, M; Lamarca, A; Krysiak, P; Bishop, P; Nonaka, D; Mansoor, W

    2017-05-01

    Pulmonary carcinoid (PC) tumours are classified as either typical (TC) or atypical (AC) according to mitotic index (MI) and presence of necrosis. The aim of this study was to analyse the diagnostic and prognostic values of the Ki-67 index in PC. Between January 2001 and March 2015, we evaluated 94 consecutive patients with a confirmed diagnosis of TC (n = 75) or AC (n = 19) at our institution. Diagnostic histology was centrally reviewed by a local expert neuroendocrine pathologist, with assessment of Ki-67, MI, and necrosis. Median patient follow-up was 35 months. Eighty-four patients who underwent curative surgical resection were included in the survival analysis for identification of prognostic factors. Ki-67 index showed high diagnostic accuracy to predict histological subtype when assessed by receiver operator characteristic curves with an area under the curve of 0.923 (95% CI 0.852-0.995, p < 0.001). Multivariate analysis showed that MI, Ki-67 index, and the presence or absence of necrosis were independent prognostic factors for relapse-free survival. Combination of MI, Ki-67, and necrosis led to the classification of patients into four different prognostic groups (very low, low, intermediate, and high risks of relapse). The current study proposes the incorporation of Ki-67 index in the prognostic classification of PC tumours. Due to the limited number of patients and length of follow-up, the current model needs validation by larger cohort studies. Nevertheless, our results suggest that Ki-67 index and MI have continuous effect on prognosis. Prognostic models incorporating multiple cutoffs of Ki-67 and MI might better predict outcome and inform clinical decisions.

  17. Prognostic significance of stem cell-related marker expression and its correlation with histologic subtypes in lung adenocarcinoma

    PubMed Central

    Park, Eunhyang; Park, Soo Young; Sun, Ping-Li; Jin, Yan; Kim, Ji Eun; Jheon, Sanghoon; Kim, Kwhanmien; Lee, Choon Taek

    2016-01-01

    Cancer stem cells (CSCs) are a small subset of tumor cells that exhibit stem cell-like properties and contribute in treatment failure. To clarify the expression and prognostic significance of several CSC markers in non-small cell lung cancer, we retrospectively analyzed 368 patients with adenocarcinoma (n = 226) or squamous cell carcinoma (n = 142). We correlated the expression of six CSC markers – CD133, CD44, aldehyde dehydrogenase 1 (ALDH1), sex determining region Y-box 2 (SOX2), octamer binding transcription factor 4 (OCT4), and Nanog – with clinicopathologic and molecular variables and survival outcomes. In adenocarcinoma, CD133, ALDH1 and CD44 expression was associated with low pathologic stage and absence of lymphovascular invasion, while Nanog expression correlated with high histologic grade, lymphatic invasion and increased expression of Snail-1, a transcription factor associated with epithelial-mesenchymal transition. CSC marker expression was also associated with histologic subtypes in adenocarcinoma. Multivariate analysis showed that high Nanog expression was an independent factor associated with a poor prognosis in adenocarcinoma. CSC markers had no prognostic value in squamous cell carcinoma. These results suggest that Nanog is an independent negative prognostic factor that may be associated with epithelial-mesenchymal transition in lung adenocarcinoma. PMID:27285762

  18. Blood Cell Palmitoleate-Palmitate Ratio Is an Independent Prognostic Factor for Amyotrophic Lateral Sclerosis

    PubMed Central

    Henriques, Alexandre; Blasco, Hélène; Fleury, Marie-Céline; Corcia, Philippe; Echaniz-Laguna, Andoni; Robelin, Laura; Rudolf, Gabrielle; Lequeu, Thiebault; Bergaentzle, Martine; Gachet, Christian; Pradat, Pierre-François; Marchioni, Eric; Andres, Christian R.; Tranchant, Christine; Gonzalez De Aguilar, Jose-Luis; Loeffler, Jean-Philippe

    2015-01-01

    Growing evidence supports a link between fatty acid metabolism and amyotrophic lateral sclerosis (ALS). Here we determined the fatty acid composition of blood lipids to identify markers of disease progression and survival. We enrolled 117 patients from two clinical centers and 48 of these were age and gender matched with healthy volunteers. We extracted total lipids from serum and blood cells, and separated fatty acid methyl esters by gas chromatography. We measured circulating biochemical parameters indicative of the metabolic status. Association between fatty acid composition and clinical readouts was studied, including ALS functional rating scale-revised (ALSFRS-R), survival, disease duration, site of onset and body mass index. Palmitoleate (16:1) and oleate (18:1) levels, and stearoyl-CoA desaturase indices (16:1/16:0 and 18:1/18:0) significantly increased in blood cells from ALS patients compared to healthy controls. Palmitoleate levels and 16:1/16:0 ratio in blood cells, but not body mass index or leptin concentrations, negatively correlated with ALSFRS-R decline over a six-month period (p<0.05). Multivariate Cox analysis, with age, body mass index, site of onset and ALSFRS-R as covariables, showed that blood cell 16:1/16:0 ratio was an independent prognostic factor for survival (hazard ratio=0.1 per unit of ratio, 95% confidence interval=0.01-0.57, p=0.009). In patients with high 16:1/16:0 ratio, survival at blood collection was extended by 10 months, as compared to patients with low ratio. The 16:1/16:0 index is an easy-to-handle parameter that predicts survival of ALS patients independently of body mass index. It therefore deserves further validation in larger cohorts for being used to assess disease outcome and effects of disease-modifying drugs. PMID:26147510

  19. Immunohistochemical analysis of molecular drivers in melanoma identifies p16 as an independent prognostic biomarker.

    PubMed

    Lade-Keller, Johanne; Riber-Hansen, Rikke; Guldberg, Per; Schmidt, Henrik; Hamilton-Dutoit, Stephen Jacques; Steiniche, Torben

    2014-06-01

    To perform immunohistochemical (IHC) analysis of molecular drivers related to the development and maintenance of melanoma and to assess their value as diagnostic and prognostic melanoma biomarkers in routine clinical practice. Tissue microarrays constructed from a cohort of primary melanomas (n=355), benign naevi (n=37) and melanoma metastases (n=14) were evaluated for IHC expression of c-KIT, BRAF(V600E), MITF, p16, p53 and PTEN, as well as for pERK, a surrogate marker for mitogen-activated protein kinase pathway activation. The results were correlated with clinicopathological parameters and clinical outcome. Absent p16 expression and reduced MITF expression were both associated with the adverse prognostic markers ulceration (p=0.009 and p<0.0001, respectively), advanced tumour stage (p<0.0001 and p=0.001, respectively) and higher Breslow thickness (both p<0.0001), as well as with an adverse overall relapse-free survival (p<0.0001 and p=0.003, respectively). Absence of p16 expression predicted overall relapse-free (p=0.02) and distant metastasis-free (p=0.04) survival, independently of Breslow thickness, ulceration and tumour stage. IHC determined p16 expression is an independent prognostic biomarker of potential value in routine melanoma diagnostic practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  20. Bi-allelic inactivation is more prevalent at relapse in multiple myeloma, identifying RB1 as an independent prognostic marker

    PubMed Central

    Chavan, S S; He, J; Tytarenko, R; Deshpande, S; Patel, P; Bailey, M; Stein, C K; Stephens, O; Weinhold, N; Petty, N; Steward, D; Rasche, L; Bauer, M; Ashby, C; Peterson, E; Ali, S; Ross, J; Miller, V A; Stephens, P; Thanendrarajan, S; Schinke, C; Zangari, M; van Rhee, F; Barlogie, B; Mughal, T I; Davies, F E; Morgan, G J; Walker, B A

    2017-01-01

    The purpose of this study is to identify prognostic markers and treatment targets using a clinically certified sequencing panel in multiple myeloma. We performed targeted sequencing of 578 individuals with plasma cell neoplasms using the FoundationOne Heme panel and identified clinically relevant abnormalities and novel prognostic markers. Mutational burden was associated with maf and proliferation gene expression groups, and a high-mutational burden was associated with a poor prognosis. We identified homozygous deletions that were present in multiple myeloma within key genes, including CDKN2C, RB1, TRAF3, BIRC3 and TP53, and that bi-allelic inactivation was significantly enriched at relapse. Alterations in CDKN2C, TP53, RB1 and the t(4;14) were associated with poor prognosis. Alterations in RB1 were predominantly homozygous deletions and were associated with relapse and a poor prognosis which was independent of other genetic markers, including t(4;14), after multivariate analysis. Bi-allelic inactivation of key tumor suppressor genes in myeloma was enriched at relapse, especially in RB1, CDKN2C and TP53 where they have prognostic significance. PMID:28234347

  1. Prognostic significance and molecular features of signet-ring cell and mucinous components in colorectal carcinoma.

    PubMed

    Inamura, Kentaro; Yamauchi, Mai; Nishihara, Reiko; Kim, Sun A; Mima, Kosuke; Sukawa, Yasutaka; Li, Tingting; Yasunari, Mika; Zhang, Xuehong; Wu, Kana; Meyerhardt, Jeffrey A; Fuchs, Charles S; Harris, Curtis C; Qian, Zhi Rong; Ogino, Shuji

    2015-04-01

    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. 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. 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) (P trend < 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 (P trend < 0.57). 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.

  2. 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

  3. Renal resistance index and its prognostic significance in patients with heart failure with preserved ejection fraction.

    PubMed

    Ennezat, Pierre Vladimir; Maréchaux, Sylvestre; Six-Carpentier, Marie; Pinçon, Claire; Sediri, Ibrahim; Delsart, Pascal; Gras, Marc; Mounier-Véhier, Claire; Gautier, Corinne; Montaigne, David; Jude, Brigitte; Asseman, Philippe; Le Jemtel, Thierry H

    2011-12-01

    Functional renal impairment is a common feature of heart failure with preserved ejection fraction (HFpEF). The link between functional renal impairment and HFpEF remains incompletely understood. With hypertension and diabetes as frequent co-morbidities, patients with HFpEF are at risk of developing intra-renal vascular hemodynamic alterations that may lead to functional renal impairment and impact on prognosis. Renal resistive index (RRI) was non-invasively determined by Doppler ultrasonic examination in 90 HFpEF patients and 90 age- and sex-matched hypertensive patients without evidence of heart failure (HF) who served as controls. Clinical, laboratory and cardiac echocardiography data were obtained in HFpEF patients and controls. To investigate its possible clinical relevance, RRI was evaluated as a prognostic index of all-cause mortality and hospitalization for HF. Mean RRI was substantially greater in HFpEF patients than in controls (P < 0.0001), while mean blood pressure, glomerular filtration rate, hemoglobin and serum protein levels were significantly lower in HFpEF patients than in controls. On multivariable analysis, mean RRI was independently associated with HFpEF. In addition, increased mean RRI was an independent predictor of poor outcome [hazard ratio = 1.06 95% confidence interval (1.01-1.10), P = 0.007] and remained significantly associated with the outcome after adjustment for univariate predictors that included low mean blood pressure, low hemoglobin concentration and low glomerular filtration rate. Conclusion. Patients with HFpEF exhibit intra-renal vascular hemodynamic alterations. The severity of intra-renal vascular hemodynamic alterations correlates with a poor outcome.

  4. Prognostic significance of vascular endothelial growth factor polymorphisms in colorectal cancer patients

    PubMed Central

    do Espírito Santo, Gilmar Ferreira; Galera, Bianca Borsatto; Duarte, Elisabeth Carmen; Chen, Elisabeth Suchi; Azis, Lenuce; Damazo, Amilcar Sabino; Saba, Gabriela Tognini; de Sousa Gehrke, Flávia; Guerreiro da Silva, Ismael Dale Cotrim; Waisberg, Jaques

    2017-01-01

    AIM To investigate the associations of the genetic polymorphisms of vascular endothelial growth factor A (VEGF-A) -1498C>T and -634G>C, with the survival of patients with colorectal cancer (CRC). METHODS A prospective cohort consisting of 131 Brazilians patients consecutively operated on with a curative intention as a result of sporadic colorectal carcinoma was studied. DNA was extracted from peripheral blood and its amplification and allelic discrimination for each genetic polymorphism was performed using the technique of polymerase chain reaction (PCR) in real-time. The real-time PCR technique was used to identify the VEGF-A -1498C>T (rs833031) and -634G>C (rs2010963) polymorphisms. Genotyping was validated for VEGF-A -1498C>T polymorphism in 129 patients and for VEGF-A -634G>C polymorphism in 118 patients. The analysis of association between categorical variables was performed using logistic regression, survival by Kaplan-Meier method and multivariate analysis by the Cox regression method. RESULTS In the univariate analysis there was a significant association (OR = 0.32; P = 0.048) between genotype CC of the VEGF-A -1498C>T polymorphism and the presence of CRC liver metastasis. There was no association between VEGF-A -1498C>T polymorphism and VEGF-A -634G>C polymorphism with further clinical or anatomopathologic variables. The genotype CC of the VEGF-A -1498C>T polymorphism was significantly correlated with the 5-year survival (P = 0.032), but not significant difference (P = 0.27) was obtained with the VEGF-A -634G>C polymorphism with the 5-year survival in the univariate analysis. The genotype CT (HR = 2.79) and CC (HR = 4.67) of the polymorphism VEGF-A -1498C>T and the genotype CC (HR = 3.76) of the polymorphism VEGF-A -634C>G acted as an independent prognostic factor for the risk of death in CRC patients. CONCLUSION The CT and CC genotypes of the VEGF-A -1498C>T and the CC genotype of the VEGF-A -634C>G polymorphisms are prognostic factors of survival in

  5. Prognostic significance of body mass index before treatment for head and neck cancer.

    PubMed

    Takenaka, Yukinori; Takemoto, Norihiko; Nakahara, Susumu; Yamamoto, Yoshifumi; Yasui, Toshimichi; Hanamoto, Atshushi; Fukusumi, Takahito; Michiba, Takahiro; Cho, Hironori; Yamamoto, Masashi; Inohara, Hidenori

    2015-10-01

    Patients with head and neck cancer frequently experience malnutrition. The purpose of this study was to examine the impact of nutritional status on prognosis and its association with treatment modalities. This retrospective study included 706 patients with head and neck cancer diagnosed between 2004 and 2012. The effects of pretreatment body mass index (BMI) on overall survival were analyzed using the Kaplan-Meier method and Cox regression model. BMI ranged from 11.6 to 38.0 kg/m2 (median, 21.5) and was a prognostic factor for survival, independent of primary site, and tumor stage. The 5-year survival rates for underweight, normal, and overweight groups were 32.2%, 62.7%, and 73.5%, respectively. The hazard ratios of BMI in the surgery, chemoradiation, and radiation groups were 0.95, 0.91, and 0.79, respectively, and the latter two were statistically significant. The impact of BMI is determined by the types of cancer treatment. Pretreatment BMI should be considered while deciding treatment. © 2014 Wiley Periodicals, Inc.

  6. Functional and prognostic significance of the genomic amplification of frizzled 6 (FZD6) in breast cancer.

    PubMed

    Corda, Gabriele; Sala, Gianluca; Lattanzio, Rossano; Iezzi, Manuela; Sallese, Michele; Fragassi, Giorgia; Lamolinara, Alessia; Mirza, Hasan; Barcaroli, Daniela; Ermler, Sibylle; Silva, Elisabete; Yasaei, Hemad; Newbold, Robert F; Vagnarelli, Paola; Mottolese, Marcella; Natali, Pier Giorgio; Perracchio, Letizia; Quist, Jelmar; Grigoriadis, Anita; Marra, Pierfrancesco; Tutt, Andrew N; Piantelli, Mauro; Iacobelli, Stefano; De Laurenzi, Vincenzo; Sala, Arturo

    2017-02-01

    Frizzled receptors mediate Wnt ligand signalling, which is crucially involved in regulating tissue development and differentiation, and is often deregulated in cancer. In this study, we found that the gene encoding the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple-negative breast cancer (TNBC) subtype. Ablation of FZD6 expression in mammary cancer cell lines: (1) inhibited motility and invasion; (2) induced a more symmetrical shape of organoid three-dimensional cultures; and (3) inhibited bone and liver metastasis in vivo. Mechanistically, FZD6 signalling is required for the assembly of the fibronectin matrix, interfering with the organization of the actin cytoskeleton. Ectopic delivery of fibronectin in FZD6-depleted, triple-negative MDA-MB-231 cells rearranged the actin cytoskeleton and restored epidermal growth factor-mediated invasion. In patients with localized, lymph node-negative (early) breast cancer, positivity of tumour cells for FZD6 protein identified patients with reduced distant relapse-free survival. Multivariate analysis indicated an independent prognostic significance of FZD6 expression in TNBC tumours, predicting distant, but not local, relapse. We conclude that the FZD6-fibronectin actin axis identified in our study could be exploited for drug development in highly metastatic forms of breast cancer, such as TNBC. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  7. High level of serum AFP is an independent negative prognostic factor in gastric cancer.

    PubMed

    Chen, Yueguang; Qu, Hui; Jian, Mi; Sun, Guorui; He, Qingsi

    2015-11-11

    Gastric cancer with a high level of serum alpha fetoprotein (AFP) is uncommon and has unique clinicopathological features and a poorer prognosis. The aim of this research was to elucidate the clinicopathological and prognostic features of gastric cancer with a high level of AFP. The sera from 1,286 patients with gastric cancer treated at Qilu Hospital of Shandong University from January 2004 to December 2008 were analyzed preoperatively for AFP, CEA and CA19-9 levels after excluding active or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma as well as preoperative distant metastasis. Patients were divided into 2 groups: 86 serum AFP-positive patients and 1,200 serum AFP-negative patients according to a cutoff of 20 ng/mL. The clinicopathological features and prognostic factors were compared between the groups. A higher incidence of serosal invasion, lymph node metastasis and liver metastasis and poorer prognosis was observed in the AFP-positive group compared with the AFP-negative group (all p<0.05). Serum AFP showed the highest specificity (93.66%) and diagnostic accuracy (92.38%) for predicting liver metastasis among the 3 tumor markers examined. Multivariate survival analysis revealed that AFP positivity was an independent prognostic factor in all 1,286 gastric cancer patients. The prognosis of AFP-positive gastric cancer was poorer than that of AFP-negative gastric cancer (p<0.05). A high level of serum AFP is an independent prognostic factor in gastric cancer and can be used for evaluating the prognosis of gastric cancers whether in the presence or absence of liver metastasis.

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

    PubMed

    El Demery, Mounira; Demirdjian-Sarkissian, Gaiané; Thezenas, Simon; Jacot, William; Laghzali, Yassine; Darbouret, Bruno; Culine, Stéphane; Rebillard, Xavier; Lamy, Pierre-Jean

    2014-01-01

    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. 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. 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). Our results show that the MMP-7 serum concentration is an independent prognostic factor in patients with locally advanced and or metastatic bladder cancer.

  9. 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

  10. Smoking habits are an independent prognostic factor in patients with lung cancer.

    PubMed

    Avci, Nilufer; Hayar, Murat; Altmisdortoglu, Ozgur; Tanriverdi, Ozgur; Deligonul, Adem; Ordu, Cetin; Evrensel, Turkkan

    2017-09-01

    The role of tobacco in the pathogenesis of lung cancer (LC) has been clearly established. Based on the epidemiological evidence that smoking may influence LC progression, we investigated the idea that smoking behavior could be associated with overall survival (OS) in this group of patients. A total of 351 patients with LC (311 men and 40 women) were reviewed. Smoking status was assessed as tobacco users or non-users. To calculate pack-years of smoking, the average of number of cigarettes smoked per day was divided by 20 to give packs per day, and then multiplied by the total number of years of smoking. OS was the main outcome measure. The mean follow-up was 3.3 ± 1.2 years. Kaplan-Meier plots of OS by use of tobacco revealed significant differences by smoking status (log-rank = 5.44, P < 0.01), indicating a reduced survival rate in tobacco users. The effect on OS of the amount of cigarette smoking was also evident when we subdivided the former and current smokers into ≤7 (mean value) pack-years and >7 pack-years groups (log-rank = 4.27, P < 0.05). After adjusting for all potential confounders, tobacco smoking retained its independent prognostic significance for OS (hazard ratio = 1.53, 95% confidence interval = 1.19-2.17, P = 0.02). Our data indicate that cigarette smoking is significantly associated with a poor prognosis among patients diagnosed with LC in a dose-dependent manner. © 2015 John Wiley & Sons Ltd.

  11. Prognostic significance of immune cells in the tumor microenvironment and peripheral blood of gallbladder carcinoma patients.

    PubMed

    Zhang, Y; Ma, C; Wang, M; Hou, H; Cui, L; Jiang, C; Sun, J; Qu, X

    2017-04-01

    The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC. 98 patients with GBC were recruited in this retrospective study. Using immunohistochemistry, we examined tumor-infiltrating CD3+ generic T-cells, CD8+ cytotoxic T-cells, CD45RO+ memory T-cells, and CD15+ neutrophils. Peripheral venous blood samples were also collected, and absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) were measured. The relationships between these variables and patient outcome were evaluated. Survival analysis revealed that the density of CD3+ cell infiltrates in the tumor microenvironment was positively correlated with overall survival (OS) and the density of CD15+ cell infiltrates was negatively correlated with the OS. The combined analysis showed that a high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates was an independent prognostic factor for GBC. In peripheral blood, survival analysis suggested that ANC and NLR were negatively correlated, while ALC was positively correlated with OS. Multivariate survival analysis showed that NLR was an independent prognostic factor for gallbladder cancer prognosis. The results indicate that the combination of high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates in tumor samples and pretreatment peripheral blood NLR were independent prognostic factors in patients with GBC.

  12. [The expression and prognostic significance of ERCC1 and GST-pi in lung cancer].

    PubMed

    Xu, Chong'an; Feng, Dan; Li, Lin; Yu, Ping; Hu, Xuejun; Liu, Yunpeng

    2010-03-01

    It has been known that the expression levels of ERCC1 and GST-pi were correlated with tumorigenesis and prognosis. The aim of this study is to investigate the relationship between expression levels of ERCC1 and GST-pi, and clinicopathologic parameters and survival in patients with lung cancer. The expression levels of ERCC1 and GST-pi were detected by immunohistochemical staining on tissue micro-array sections made of 148 cases of lung cancer and 7 cases of normal lung samples. The results were compared with relevant clinical and pathologic data. Positive rates of ERCC1 and GST-pi were 36.2% and 73.6%, respectively. None of normal lung samples was positive staining. Positive expression of ERCC1 was significantly higher in group of non-small cell lung cancer (NSCLC), highly differentiated and the smokers less than 400 (P < 0.05), positive expression of GST-pi was significantly higher in group of non-smokers and NSCLC (P < 0.05). There were significant correlations between expression of ERCC1 and GST-pi (r = 0.253, P = 0.001). The 5 years survival rate was higher in positive expression of ERCC1. There was significant correlations between expression of ERCC1 and survival (P = 0.037). There was no significant correlations between expression of GST-pi and survival (P = 0.614). Multivariate analysis using Cox regression model showed that expression levels of ERCC1 and GST-pi were not the important independent prognostic factors for survival. ERCC1 and GST-pi are aberrant highly expressed in NSCLC with positive correlation, which indicate they might act synergistically in tumorigenesis of NSCLC. The positive expression of ERCC1 have better survival and may have effect on prognosis.

  13. Clinicopathologic and prognostic significance of c-MYC copy number gain in lung adenocarcinomas

    PubMed Central

    Seo, A N; Yang, J M; Kim, H; Jheon, S; Kim, K; Lee, C T; Jin, Y; Yun, S; Chung, J-H; Paik, J H

    2014-01-01

    Background: c-MYC copy number gain (c-MYC gain) has been associated with aggressive behaviour in several cancers. However, the role of c-MYC gain has not yet been determined in lung adenocarcinomas classified by genetic alterations in epidermal growth factor receptor (EGFR), KRAS, and anaplastic lymphoma kinase (ALK) genes. We investigated the clinicopathologic and prognostic significance of c-MYC gain for disease-free survival (DFS) and overall survival (OS) according to EGFR, KRAS, and ALK gene status and stages in lung adenocarcinomas. Methods: In 255 adenocarcinomas resected in Seoul National University Bundang Hospital from 2003 to 2009, fluorescence in situ hybridisation (FISH) with c-MYC probe and centromeric enumeration probe 8 (CEP8) was analysed using tissue microarray containing single representative core per each case. EGFR (codon 18 to 21) and KRAS (codon 12, 13, and 61) mutations were analysed by polymerase chain reaction and direct sequencing method from formalin-fixed, paraffin-embedded tissue sections. ALK rearrangement was determined by FISH method. c-MYC gain was defined as >2 copies per nucleus, chromosome 8 gain as ⩾3 copies per nucleus, and gain of c-MYC:CEP8 ratio (hereafter, c-MYC amplification) as ⩾2. Results: We observed c-MYC gain in 20% (51 out of 255), chromosome 8 gain in 5.5% (14 out of 255), c-MYC amplification in 2.4% (6 out of 255), EGFR mutation in 49.4% (118 out of 239), KRAS mutation in 5.7% (7 out of 123), and ALK rearrangement in 4.9% (10 out of 205) of lung adenocarcinomas. c-MYC gain was observed in 19% (22 out of 118) of patients with lung adenocarcinomas with an EGFR mutation, but not in any patients with a KRAS mutation, or an ALK rearrangement. c-MYC gain (but not chromosome 8 gain or c-MYC amplification) was an independent poor-prognostic factor in the full cohort of lung adenocarcinoma (P=0.022, hazard ratio (HR)=1.71, 95% confidence interval (CI), 1.08–2.69 for DFS; P=0.032, HR=2.04, 95% CI, 1.06–3.91 for OS

  14. 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.

  15. Entropy-based adaptive nuclear texture features are independent prognostic markers in a total population of uterine sarcomas.

    PubMed

    Nielsen, Birgitte; Hveem, Tarjei Sveinsgjerd; Kildal, Wanja; Abeler, Vera M; Kristensen, Gunnar B; Albregtsen, Fritz; Danielsen, Håvard E

    2015-04-01

    Nuclear texture analysis measures the spatial arrangement of the pixel gray levels in a digitized microscopic nuclear image and is a promising quantitative tool for prognosis of cancer. The aim of this study was to evaluate the prognostic value of entropy-based adaptive nuclear texture features in a total population of 354 uterine sarcomas. Isolated nuclei (monolayers) were prepared from 50 µm tissue sections and stained with Feulgen-Schiff. Local gray level entropy was measured within small windows of each nuclear image and stored in gray level entropy matrices, and two superior adaptive texture features were calculated from each matrix. The 5-year crude survival was significantly higher (P < 0.001) for patients with high texture feature values (72%) than for patients with low feature values (36%). When combining DNA ploidy classification (diploid/nondiploid) and texture (high/low feature value), the patients could be stratified into three risk groups with 5-year crude survival of 77, 57, and 34% (Hazard Ratios (HR) of 1, 2.3, and 4.1, P < 0.001). Entropy-based adaptive nuclear texture was an independent prognostic marker for crude survival in multivariate analysis including relevant clinicopathological features (HR = 2.1, P = 0.001), and should therefore be considered as a potential prognostic marker in uterine sarcomas.

  16. 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. PMID:27478321

  17. Prevalence, determinants, and prognostic significance of delirium in patients with acute heart failure.

    PubMed

    Honda, Satoshi; Nagai, Toshiyuki; Sugano, Yasuo; Okada, Atsushi; Asaumi, Yasuhide; Aiba, Takeshi; Noguchi, Teruo; Kusano, Kengo; Ogawa, Hisao; Yasuda, Satoshi; Anzai, Toshihisa

    2016-11-01

    Delirium is a serious syndrome in critically ill patients. However, the prognostic impact of delirium and its determinants in acute heart failure (AHF) patients have not been fully elucidated. We examined 611 AHF patients who were admitted to our institution. Delirium was diagnosed based on the Intensive Care Delirium Screening Checklist (ICDSC). Delirium developed in 139 patients (23%) during hospitalization. Patients with delirium had higher incidence of non-cardiovascular death (p=0.046) and worsening heart failure (p<0.001) during hospitalization. Among patients who survived at discharge, the incidence of all-cause death, cardiovascular death and non-cardiovascular death after discharge were significantly higher in patients with delirium than those without (log-rank; p<0.001, p=0.001, p<0.001, respectively) during a median follow-up period of 335days. In multivariable model, the development of delirium was an independent determinant of worsening heart failure during hospitalization (OR: 2.44, 95% CI: 1.27-4.63) and all-cause death after discharge (HR: 2.38, 95% CI: 1.30-4.35). Furthermore, multivariate analysis indicated that history of cerebrovascular disease (OR: 2.13, 95% CI: 1.36-3.35), age (OR: 1.43, 95% CI: 1.15-1.80), log BNP (OR: 1.39, 95% CI: 1.09-1.79), serum albumin (OR: 0.84, 95% CI: 0.76-0.93) and blood glucose levels (OR: 1.03, 95% CI: 1.00-1.06) were independent determinants of delirium. In patients with AHF, the development of delirium was associated with poor clinical outcomes, suggesting the importance of early screening and careful monitoring of delirium in such patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Target organ complications and prognostic significance of alerting reaction: analysis from the Dallas Heart Study.

    PubMed

    Velasco, Alejandro; Ayers, Colby; Das, Sandeep R; de Lemos, James A; Khera, Amit; Victor, Ronald G; Kaplan, Norman M; Vongpatanasin, Wanpen

    2016-02-01

    Noninvasive blood pressure (BP) measurement often triggers a transient rise in BP, known as an alerting reaction. However, the prevalence and prognostic significance of the alerting reaction has never been assessed in the general population. We evaluated the association between the alerting reaction and left ventricular mass by MRI and urinary albumin-to-creatinine ratio in the Dallas Heart Study, a large population sample of 3069 individuals. Participants were categorized into four groups based on levels of consecutive BP: first, normal first BP and average third to fifth (avg3-5) BP of less than 140/90 mmHg (control group); second, high first BP of at least 140/90 mmHg and normal (avg3-5) BP (alerting reaction group); third, normal first BP and high (avg3-5) BP; and fourth, high first to fifth BP. Then, associations between BP categories with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9.4 years were assessed. The sample-weighted prevalence of isolated hypertension during the first BP measurement was 9.6%. Presence of an alerting reaction was independently associated with increased left ventricular mass, urinary albumin-to-creatinine ratio, cardiovascular events after adjustment for traditional cardiovascular risk factors, and baseline BP (adjusted hazard ratio 1.24, 95% confidence interval 1.07-1.43). Our study indicated that the alerting reaction is independently associated with increased cardiovascular and renal complications.

  19. Target Organ Complications and Prognostic Significance of Alerting Reaction: Analysis from the Dallas Heart Study

    PubMed Central

    Velasco, Alejandro; Ayers, Colby; Das, Sandeep R.; de Lemos, James A.; Khera, Amit; Victor, Ronald G.; Kaplan, Norman M.; Vongpatanasin, Wanpen

    2016-01-01

    Objective Noninvasive BP measurement often triggers a transient rise in BP, known as an alerting reaction. However, the prevalence and prognostic significance of the alerting reaction has never been assessed in the general population. Methods We evaluated the association between the alerting reaction and left ventricular mass (LVM) by magnetic resonance imaging and urinary-albumin-to-creatinine ratio (UACR) in the Dallas Heart Study, a large population sample of 3,069 subjects. Participants were categorized into 4 groups based on levels of consecutive BP: 1.normal 1st BP and average 3rd to 5th (avg3-5) BP of <140/90 mmHg (control group), 2.high 1st BP of ≥140/90 mmHg and normal (avg3-5) BP (HN), 3.normal 1st BP and high (avg3-5) BP, and 4.high 1st to 5th BP. Then, associations between BP categories with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9.4 years were assessed. Results The sample-weighted prevalence of isolated hypertension during the first BP measurement was 9.6%. Presence of an alerting reaction was independently associated with increased LVM, UACR, cardiovascular events after adjustment for traditional cardiovascular risk factors and baseline BP (adjusted HR 1.24, 95%CI 1.07-1.43). Conclusions Our study indicated that the alerting reaction is independently associated with increased cardiovascular and renal complications. PMID:26485459

  20. Revised International Prognostic Scoring System (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO Prognostic Scoring System: validation by the Gruppo Romano Mielodisplasie Italian Regional Database.

    PubMed

    Voso, Maria Teresa; Fenu, Susanna; Latagliata, Roberto; Buccisano, Francesco; Piciocchi, Alfonso; Aloe-Spiriti, Maria Antonietta; Breccia, Massimo; Criscuolo, Marianna; Andriani, Alessandro; Mancini, Stefano; Niscola, Pasquale; Naso, Virginia; Nobile, Carolina; Piccioni, Anna Lina; D'Andrea, Mariella; D'Addosio, Ada; Leone, Giuseppe; Venditti, Adriano

    2013-07-20

    The definition of disease-specific prognostic scores plays a fundamental role in the treatment decision-making process in myelodysplastic syndrome (MDS), a group of myeloid disorders characterized by a heterogeneous clinical behavior. We applied the recently published Revised International Prognostic Scoring System (IPSS-R) to 380 patients with MDS, registered in an Italian regional database, recruiting patients from the city of Rome (Gruppo Romano Mielodisplasie). Patients were selected based on the availability of IPSS-R prognostic factors, including complete peripheral-blood and bone marrow counts, informative cytogenetics, and follow-up data. We validated the IPSS-R score as a significant predictor of overall survival (OS) and leukemia-free survival (LFS) in MDS (P < .001 for both). When comparing the prognostic value of the International Prognostic Scoring System (IPSS), WHO Prognostic Scoring System (WPSS), and IPSS-R, using the Cox regression model and the likelihood ratio test, a significantly higher predictive power for LFS and OS became evident for the IPSS-R, compared with the IPSS and WPSS (P < .001 for both). The multivariate analysis, including IPSS, WPSS, age, lactate dehydrogenase, ferritin concentration, Eastern Cooperative Oncology Group performance status, transfusion dependency, and type of therapy, confirmed the significant prognostic value of IPSS-R subgroups for LFS and OS. Treatment with lenalidomide and erythropoiesis-stimulating agents was shown to be an independent predictor of survival in the multivariate analysis. Our data confirm that the IPSS-R is an excellent prognostic tool in MDS in the era of disease-modifying treatments. The early recognition of patients at high risk of progression to aggressive disease may optimize treatment timing in MDS.

  1. MYBL2 is an independent prognostic marker that has tumor-promoting functions in colorectal cancer

    PubMed Central

    Ren, Fei; Wang, Lisha; Shen, Xiaohan; Xiao, Xiuying; Liu, Zebing; Wei, Ping; Wang, Yiqin; Qi, Peng; Shen, Chen; Sheng, Weiqi; Du, Xiang

    2015-01-01

    The MYBL2 gene plays an important role in the genesis and progression of tumors; however, few studies to date have defined the role of this gene in colorectal cancer (CRC). The aim of this study was to determine the relationship between MYBL2 and the prognosis of patients with CRC and to determine the possible effect of MYBL2 on colorectal carcinogenesis. Solid CRC tissues (n=180) preserved with RNAlater were collected to examine the mRNA levels of MYBL2 by real-time quantitative PCR (RT-qPCR). Formalin-fixed, paraffin-embedded (FFPE) blocks of CRC tissues (n=97) and adjacent noncancerous tissues (ANCTs, n=104) were obtained to detect MYBL2 protein levels by immunohistochemistry (IHC). siRNA was used to downregulate MYBL2 expression in the SW480 cell line to detect changes in proliferation, cell cycle progression, apoptosis, migration and invasion. The protein levels of MYBL2 were significantly higher in CRC tissues compared with ANCTs (P<0.05). Kaplan-Meier survival curves indicated that disease-free survival (DFS) was significantly worse in CRC patients in whom MYBL2 was overexpressed (at both the mRNA and protein levels) compared with patients not overexpressing MYBL2. Cox multivariate analysis revealed MYBL2 overexpression as an independent prognostic factor for poor patient survival. In addition, siRNA downregulation of MYBL2 suppressed SW480 cell proliferation, delayed cell cycle progression and induced apoptosis; however, changes in cell migration were minor. Western blot analysis demonstrated an association between MYBL2 expression and that of MMP9, Vimentin, and E-cadherin. MYBL2 is overexpressed in CRC and may therefore play an important role in tumourigenesis. PMID:26101717

  2. B7-H6 protein expression has no prognostic significance in human gastric carcinoma.

    PubMed

    Chen, Xiao-Juan; Shen, Jin; Zhang, Guang-Bo; Chen, Wei-Chang

    2014-01-01

    B7-H6, a novel member of the B7 family which binds to NKp30 to trigger antitumor NK cell cytotoxicity and cytokine secretion. Recently, B7-H family has been reported to be a negative regulator of the immune response in patients with gastric carcinoma. However, no reports have investigated the clinical significance of B7-H6 expression in human gastric cancer. We present the first study to the clinicopathological and prognostic value of B7-H6 in primary gastric tumors and adjacent non-tumor tissues at the protein level. Here we show that B7-H6 immunoreactivity was expressed in 6/60 (10%) gastric tumors and 8/43 (18.60%) adjacent non-tumor tissues. No statistical difference was found between B7-H6 expression and various prognostic factors; however, B7-H6-positive carcinomas were significantly associated with a higher differentiation (p = 0.047). The survival analysis did not confirm the prognostic significance of B7-H6 expression in gastric cancer patients. Our data suggest that B7-H6, as detected by immunohistochemistry, is of limited value as a prognostic marker for gastric cancer.

  3. 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

  4. Systematic analysis of tumour cell-extracellular matrix adhesion identifies independent prognostic factors in breast cancer

    PubMed Central

    Wong, Jocelyn P.; Natrajan, Rachael C.; Yuan, Yinyin; Tan, Aik-Choon; Huang, Paul H.

    2016-01-01

    Tumour cell-extracellular matrix (ECM) interactions are fundamental for discrete steps in breast cancer progression. In particular, cancer cell adhesion to ECM proteins present in the microenvironment is critical for accelerating tumour growth and facilitating metastatic spread. To assess the utility of tumour cell-ECM adhesion as a means for discovering prognostic factors in breast cancer survival, here we perform a systematic phenotypic screen and characterise the adhesion properties of a panel of human HER2 amplified breast cancer cell lines across six ECM proteins commonly deregulated in breast cancer. We determine a gene expression signature that defines a subset of cell lines displaying impaired adhesion to laminin. Cells with impaired laminin adhesion showed an enrichment in genes associated with cell motility and molecular pathways linked to cytokine signalling and inflammation. Evaluation of this gene set in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort of 1,964 patients identifies the F12 and STC2 genes as independent prognostic factors for overall survival in breast cancer. Our study demonstrates the potential of in vitro cell adhesion screens as a novel approach for identifying prognostic factors for disease outcome. PMID:27556857

  5. Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

    PubMed Central

    Hose, Dirk; Rème, Thierry; Hielscher, Thomas; Moreaux, Jérôme; Messner, Tobias; Seckinger, Anja; Benner, Axel; Shaughnessy, John D.; Barlogie, Bart; Zhou, Yiming; Hillengass, Jens; Bertsch, Uta; Neben, Kai; Möhler, Thomas; Rossi, Jean François; Jauch, Anna; Klein, Bernard; Goldschmidt, Hartmut

    2011-01-01

    Background Proliferation of malignant plasma cells is a strong adverse prognostic factor in multiple myeloma and simultaneously targetable by available (e.g. tubulin polymerase inhibitors) and upcoming (e.g. aurora kinase inhibitors) compounds. Design and Methods We assessed proliferation using gene expression-based indices in 757 samples including independent cohorts of 298 and 345 samples of CD138-purified myeloma cells from previously untreated patients undergoing high-dose chemotherapy, together with clinical prognostic factors, chromosomal aberrations, and gene expression-based high-risk scores. Results In the two cohorts, 43.3% and 39.4% of the myeloma cell samples showed a proliferation index above the median plus three standard deviations of normal bone marrow plasma cells. Malignant plasma cells of patients in advanced stages or those harboring disease progression-associated gain of 1q21 or deletion of 13q14.3 showed significantly higher proliferation indices; patients with gain of chromosome 9, 15 or 19 (hyperdiploid samples) had significantly lower proliferation indices. Proliferation correlated with the presence of chromosomal aberrations in metaphase cytogenetics. It was significantly predictive for event-free and overall survival in both cohorts, allowed highly predictive risk stratification (e.g. event-free survival 12.7 versus 26.2 versus 40.6 months, P<0.001) of patients, and was largely independent of clinical prognostic factors, e.g. serum β2-microglobulin, International Staging System stage, associated high-risk chromosomal aberrations, e.g. translocation t(4;14), and gene expression-based high-risk scores. Conclusions Proliferation assessed by gene expression profiling, being independent of serum-β2-microglobulin, International Staging System stage, t(4;14), and gene expression-based risk scores, is a central prognostic factor in multiple myeloma. Surrogating a biological targetable variable, gene expression-based assessment of proliferation

  6. Prognostic significance of PIK3CA and SOX2 in Asian patients with lung squamous cell carcinoma.

    PubMed

    Iijima, Yoshihito; Seike, Masahiro; Noro, Rintaro; Ibi, Takayuki; Takeuchi, Shingo; Mikami, Iwao; Koizumi, Kiyoshi; Usuda, Jitsuo; Gemma, Akihiko

    2015-02-01

    The recent development of human genome studies has demonstrated the possibility of alteration of several genes as oncogenic driver mutations of lung squamous cell carcinoma (SQCC). FGFR1, PIK3CA and SOX2 genes have been recognized as candidate driver genes of SQCC. The aim of the present study was to evaluate FGFR1, PIK3CA and SOX2 protein expression in SQCC and determine whether the expression of these can be used as prognostic biomarkers. We evaluated the relationships between FGFR1, PIK3CA and SOX2 expression by immunohistochemical analysis and overall survival in lung SQCC patients with stage I-III that originated from China, United States and Japan. FGFR1-positive, PIK3CA-negative and SOX2-positive staining each showed trends toward better survival, although the differences were not statistically significant in a Chinese cohort of 57 patients. Patients with PIK3CA-negative and SOX2-positive staining (PIK3CA(-)/SOX2(+)) showed better prognosis compared with those with PIK3CA-positive or SOX2-negative staining in the Chinese cohort (p=0.04). The robustness of PIK3CA(-)/SOX2(+) classification as having prognostic significance was validated in an independent set of 66 Japanese cohort patients (p=0.007). Japanese SQCC patients with stage I were evaluated separately and PIK3CA(-)/SOX2(+) cases had significantly better survival than the group with PIK3CA-positive or SOX2-negative status (p=0.03). In univariate and multivariable Cox proportional hazards models of Asian stage I patients, the PIK3CA(-)/SOX2(+) classification was statistically significantly associated with survival and was an independent prognostic factor. Classification by PIK3CA and SOX2 protein expression is useful for predicting the prognosis of Asian patients with lung SQCC with stage I.

  7. The preoperative alkaline phosphatase-to-platelet ratio index is an independent prognostic factor for hepatocellular carcinoma after hepatic resection

    PubMed Central

    Yu, Ya-Qun; Li, Jun; Liao, Yan; Chen, Qian; Liao, Wei-Jia; Huang, Jian

    2016-01-01

    Abstract A simple, inexpensive, and readily available prognostic index is highly needed to accurately predict the prognosis of hepatocellular carcinoma (HCC). This study aimed to develop a simple prognostic index using routine laboratory tests, alkaline phosphatase-to-platelet count ratio index (APPRI), to predict the likelihood of postoperative survival in HCC patients. A total of 246 patients with HCC undergoing curative resection were retrospectively analyzed. Cutoff point for APPRI was calculated using receiver operating characteristic curve analysis, and then the patients were divided into the low-APPRI group (APPRI ≤ 4.0) and the high-APPRI group (APPRI > 4.0). The influences of APPRI on disease-free survival (DFS) and overall survival (OS) were tested by the Kaplan–Meier method, and multivariate analysis using Cox regression. Elevated APPRI was associated with age, cirrhosis, and aspartate aminotransferase (AST) in HCC. Univariate analysis showed that APPRI > 4.0, tumor size >6 cm, multiple tumors, Barcelona-clinic liver cancer stages B to C, and AST > 40 U/L were significant predictors of worse DFS and OS. A multivariate analysis suggested that APPRI > 4.0 was an independent factor for DFS (hazard ratio [HR] = 1.689; 95% confidence interval [CI], 1.139–2.505; P = 0.009) and OS (HR = 1.664; 95% CI, 1.123–2.466; P = 0.011). Preoperative APPRI > 4.0 was a powerful prognostic predictor of adverse DFS and OS in HCC after surgery. The APPRI may be a promising prognostic marker for HCC after surgical resection. PMID:28002346

  8. Fractal Characteristics of May-Grünwald-Giemsa Stained Chromatin Are Independent Prognostic Factors for Survival in Multiple Myeloma

    PubMed Central

    Ferro, Daniela P.; Falconi, Monica A.; Adam, Randall L.; Ortega, Manoela M.; Lima, Carmen P.; de Souza, Carmino A.; Lorand-Metze, Irene; Metze, Konradin

    2011-01-01

    Background The use of computerized image analysis for the study of nuclear texture features has provided important prognostic information for several neoplasias. Recently fractal characteristics of the chromatin structure in routinely stained smears have shown to be independent prognostic factors in acute leukemia. In the present study we investigated the influence of the fractal dimension (FD) of chromatin on survival of patients with multiple myeloma. Methodology We analyzed 67 newly diagnosed patients from our Institution treated in the Brazilian Multiple Myeloma Study Group. Diagnostic work-up consisted of peripheral blood counts, bone marrow cytology, bone radiograms, serum biochemistry and cytogenetics. The International Staging System (ISS) was used. In every patient, at least 40 digital nuclear images from diagnostic May-Grünwald-Giemsa stained bone marrow smears were acquired and transformed into pseudo-3D images. FD was determined by the Minkowski-Bouligand method extended to three dimensions. Goodness-of-fit of FD was estimated by the R2 values in the log-log plots. The influence of diagnostic features on overall survival was analyzed in Cox regressions. Patients that underwent autologous bone marrow transplantation were censored at the day of transplantation. Principal Findings Median age was 56 years. According to ISS, 14% of the patients were stage I, 39% were stage II and 47% were stage III. Additional features of a bad prognosis were observed in 46% of the cases. When stratifying for ISS, both FD and its goodness-of-fit were significant prognostic factors in univariate analyses. Patients with higher FD values or lower goodness-of-fit showed a worse outcome. In the multivariate Cox-regression, FD, R2, and ISS stage entered the final model, which showed to be stable in a bootstrap resampling study. Conclusions Fractal characteristics of the chromatin texture in routine cytological preparations revealed relevant prognostic information in patients with

  9. An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation.

    PubMed

    Candido Dos Reis, Francisco J; Wishart, Gordon C; Dicks, Ed M; Greenberg, David; Rashbass, Jem; Schmidt, Marjanka K; van den Broek, Alexandra J; Ellis, Ian O; Green, Andrew; Rakha, Emad; Maishman, Tom; Eccles, Diana M; Pharoah, Paul D P

    2017-05-22

    PREDICT is a breast cancer prognostic and treatment benefit model implemented online. The overall fit of the model has been good in multiple independent case series, but PREDICT has been shown to underestimate breast cancer specific mortality in women diagnosed under the age of 40. Another limitation is the use of discrete categories for tumour size and node status resulting in 'step' changes in risk estimates on moving between categories. We have refitted the PREDICT prognostic model using the original cohort of cases from East Anglia with updated survival time in order to take into account age at diagnosis and to smooth out the survival function for tumour size and node status. Multivariable Cox regression models were used to fit separate models for ER negative and ER positive disease. Continuous variables were fitted using fractional polynomials and a smoothed baseline hazard was obtained by regressing the baseline cumulative hazard for each patients against time using fractional polynomials. The fit of the prognostic models were then tested in three independent data sets that had also been used to validate the original version of PREDICT. In the model fitting data, after adjusting for other prognostic variables, there is an increase in risk of breast cancer specific mortality in younger and older patients with ER positive disease, with a substantial increase in risk for women diagnosed before the age of 35. In ER negative disease the risk increases slightly with age. The association between breast cancer specific mortality and both tumour size and number of positive nodes was non-linear with a more marked increase in risk with increasing size and increasing number of nodes in ER positive disease. The overall calibration and discrimination of the new version of PREDICT (v2) was good and comparable to that of the previous version in both model development and validation data sets. However, the calibration of v2 improved over v1 in patients diagnosed under the age

  10. KIT is an independent prognostic marker for pancreatic endocrine tumors: a finding derived from analysis of islet cell differentiation markers.

    PubMed

    Zhang, Lizhi; Smyrk, Thomas C; Oliveira, Andre M; Lohse, Christine M; Zhang, Shuya; Johnson, Michele R; Lloyd, Ricardo V

    2009-10-01

    Prediction of the biologic behavior of pancreatic endocrine tumor (PET) without local invasion or metastasis is often difficult. The 2004 World Health Organization (WHO) classification uses size, angioinvasion, mitotic activity, and Ki-67 index as prognostic criteria. Recently, cytokeratin 19 (CK19) was shown to be another prognostic marker, but the mechanism by which CK19 predicts prognosis is unknown. As CK19 is the first cytokeratin expressed in all epithelial cells in fetal pancreas, we sought to test expression of other markers of islet cell differentiation including KIT, Pdx-1, Pax4, and Pax6 in PET and correlation of these markers with clinical behavior. Clinical information and histology was reviewed in 97 PETs. All tumors were classified according to WHO criteria and a tumor, node, and metastases stage system. Immunohistochemistry was performed using antibodies to Ki-67, KIT, CK19, Pdx-1, Pax4, and Pax6. Associations of clinicopathologic and immunohistochemical features with prognosis were evaluated using Cox proportional hazards regression models. WHO and tumor, node, and metastases classifications, mitotic counts and Ki-67 labeling, infiltrative border, necrosis, perineural invasion, extrapancreatic extension, tumor size, and positive CK19 and KIT expression were significantly associated with death from disease in a univariate setting. In multivariate analysis, only WHO criteria and KIT expression were shown to be independent. An immunohistochemical classification system was derived from a combination of KIT and CK19 expression: low risk (KIT-/CK19-), intermediate risk (KIT-/CK19+), and high risk (KIT+/CK19+). Survival, metastases, and recurrence of PET were significantly different among the 3 groups. These results indicate that KIT is a new and independent prognostic marker for PETs. The classification system derived from KIT and CK19 was able to predict clinical behavior of PET.

  11. Prognostic significance of elevated troponin in non-cardiac hospitalized patients: a systematic review and meta-analysis.

    PubMed

    Ahmed, Amna N; Blonde, Ken; Hackam, Daniel; Iansavichene, Alla; Mrkobrada, Marko

    2014-12-01

    Cardiac biomarker troponin can be elevated in patients without a primary cardiac diagnosis and may have prognostic value. We conducted a systematic review to estimate the prevalence and prognostic significance of elevated troponin levels in patients admitted to hospital without a primary cardiac diagnosis. Literature search was done using MEDLINE (1946 to November 2012), EMBASE (1974 to Week 45, 2012), and Cochrane Central Register of Controlled Trials (November 2012). Two independent investigators reviewed full-text studies for final inclusion. We included studies of patients admitted without a primary cardiac diagnosis. Eligible studies compared adverse outcomes in patients with normal versus elevated troponin levels. Twenty-seven studies were included in the meta-analysis. Elevated troponin was associated with increased in-hospital and 30-day mortality (25 studies, 7255 patients, OR 3.88, 95% CI 2.90-5.19, P < 0.0001). Elevated troponin was also associated with increased risk of long-term mortality at 6 months (9 studies, 5368 patients, OR 4.21, 95% CI 1.84-9.64, P < 0.00001). Troponin is an independent predictor of short-term mortality with a pooled adjusted OR of 2.36, 95% CI 1.47-3.76, P < 0.0003. In conclusion, elevated troponin in non-cardiac patients is independently associated with increased mortality.

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

    PubMed

    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.

  13. Social class is an important and independent prognostic factor of breast cancer mortality.

    PubMed

    Bouchardy, Christine; Verkooijen, Helena M; Fioretta, Gérald

    2006-09-01

    Reasons of the important impact of socioeconomic status on breast cancer prognosis are far from established. This study aims to evaluate and explain the social disparities in breast cancer survival in the Swiss canton of Geneva, where healthcare costs and life expectancy are among the highest in the world. This population-based study included all 3,920 female residents of Geneva, who were diagnosed with invasive breast cancer before the age of 70 years between 1980 and 2000. Patients were divided into 4 socioeconomic groups, according to the woman's last occupation. We used Cox multivariate regression analysis to identify reasons for the socioeconomic inequalities in breast cancer survival. Compared to patients of high social class, those of low social class had an increased risk (unadjusted hazard ratio [HR] 2.4, 95% CI: 1.6-3.5) of dying as a result of breast cancer. These women were more often foreigners, less frequently had screen-detected cancer and were at more advanced stage at diagnosis. They less frequently underwent breast-conserving surgery, hormonal therapy, and chemotherapy, in particular, in case of axillary lymph node involvement. When adjusting for all these factors, patients of low social class still had a significantly increased risk of dying of breast cancer (HR 1.8, 95% CI: 1.2-2.6). Overmortality linked to low SES is only partly explained by delayed diagnosis, unfavorable tumor characteristics and suboptimal treatments. Other factors, not measured in this study, also could play a role. While waiting for the outcome of other researches, we should consider socioeconomic status as an independent prognostic factor and provide intensified support and surveillance to women of low social class. Copyright 2006 Wiley-Liss, Inc.

  14. Prognostic Significance of Pre-treatment Serum C-Reactive Protein Level in Patients with Adenocarcinoma of the Uterine Cervix.

    PubMed

    Bodner-Adler, Barbara; Kimberger, Oliver; Schneidinger, Cora; Kölbl, Heinz; Bodner, Klaus

    2016-09-01

    To evaluate pre-treatment serum C-reactive protein (CRP) level as a prognostic parameter in patients with adenocarcinoma of the uterine cervix. Pre-treatment CRP levels were analyzed to determine potential associations with clinicopathological parameters and to assess prognostic value in 46 patients with sole adenocarcinoma of the uterine cervix. The mean (±SD) pre-treatment serum CRP level was 5.82 (7.21) mg/l. Serum CRP concentration significantly correlated positively with age at diagnosis (p=0.001), lymphovascular space invasion (p=0.0026), recurrent disease (p=0.0001) and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.0002). In multivariate Cox regression models with age, FIGO stage, histological grade and lymph node status, elevated CRP and cancer antigen 125 levels were associated with shortened survival (p<0.05). Overall 5-year survival rate of patients with pre-treatment serum CRP level <5.0 mg/l was 100% compared to 46.9% for patients with pre-treatment CRP level ≥5.0 mg/l. Serum CRP level can be seen as an additional independent prognostic parameter in patients with the rare histological subtype adenocarcinoma of the uterine cervix. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  15. Prognostic significance of chemotherapy-induced necrosis in osteosarcoma patients receiving pasteurized autografts

    PubMed Central

    Joo, Min Wook; Kang, Yong Koo; Yoo, Chang-Young; Cha, Sung Ho

    2017-01-01

    Background Among various reconstruction methods after wide excision for osteosarcoma, pasteurized autograft is often preferred. While the whole area of the tumor can be assessed for chemotherapy-induced necrosis, one of the important prognostic factors, in other reconstructive techniques, only a portion removed from a wide-resection specimen is available when using pasteurized autograft method. The assessment, therefore, may be unreliable. We analyzed the prognostic significance of the chemotherapy-induced necrosis in osteosarcoma patients who underwent reconstruction with pasteurized autografts. Patients and methods We reviewed the records of osteosarcoma patients who underwent treatment in our institution from 1998 to 2013. Cases of reconstruction with pasteurized autografts were defined as the patient group, and the same number of patients who underwent other reconstruction methods served as controls. Chemotherapy-induced necrosis was evaluated for removed extra-osseous and curetted intramedullary tumor tissues. Results A total of 22 patients were identified; the median age was 15.5 years, and there were 12 males. The most common tumor location was the distal femur. The most common histological subtype was osteoblastic. Median size was 8.1 cm. Disease status was stage IIB in 13 patients and IIA in 9. Median follow-up was 76 months. No differences between the patient and control groups were observed in potential prognostic factors, overall survival, metastasis-free survival, or recurrence-free survival. Univariate analyses demonstrated that histological response was a significant prognostic factor for metastasis-free survival and also significant for recurrence-free survival. Conclusion Chemotherapy-induced necrosis grading, using only available tumor tissues, could be a prognostic factor for osteosarcoma patients receiving pasteurized autografts for reconstructive surgery. PMID:28196121

  16. Prognostic Significance of Remote Myocardium Alterations Assessed by Quantitative Noncontrast T1 Mapping in ST-Segment Elevation Myocardial Infarction.

    PubMed

    Reinstadler, Sebastian J; Stiermaier, Thomas; Liebetrau, Johanna; Fuernau, Georg; Eitel, Charlotte; de Waha, Suzanne; Desch, Steffen; Reil, Jan-Christian; Pöss, Janine; Metzler, Bernhard; Lücke, Christian; Gutberlet, Matthias; Schuler, Gerhard; Thiele, Holger; Eitel, Ingo

    2017-06-09

    This study assessed the prognostic significance of remote zone native T1 alterations for the prediction of clinical events in a population with ST-segment elevation myocardial infarction (STEMI) who were treated by primary percutaneous coronary intervention (PPCI) and compared it with conventional markers of infarct severity. The exact role and incremental prognostic relevance of remote myocardium native T1 mapping alterations assessed by cardiac magnetic resonance (CMR) after STEMI remains unclear. We included 255 consecutive patients with STEMI who were reperfused within 12 h after symptom onset. CMR core laboratory analysis was performed to assess left ventricular (LV) function, standard infarct characteristics, and native T1 values of the remote, noninfarcted myocardium. The primary endpoint was a composite of death, reinfarction, and new congestive heart failure within 6 months (major adverse cardiac events [MACE]). Patients with increased remote zone native T1 values (>1,129 ms) had significantly larger infarcts (p = 0.012), less myocardial salvage (p = 0.002), and more pronounced LV dysfunction (p = 0.011). In multivariable analysis, remote zone native T1 was independently associated with MACE after adjusting for clinical risk factors (p = 0.001) or other CMR variables (p = 0.007). In C-statistics, native T1 of remote myocardium provided incremental prognostic information beyond clinical risk factors, LV ejection fraction, and other markers of infarct severity (all p < 0.05). The addition of remote zone native T1 to a model of prognostic CMR parameters (ejection fraction, infarct size, and myocardial salvage index) led to net reclassification improvement of 0.82 (95% confidence interval: 0.46 to 1.17; p < 0.001) and to an integrated discrimination improvement of 0.07 (95% confidence interval: 0.02 to 0.13; p = 0.01). In STEMI patients treated by PPCI, evaluation of remote zone alterations by quantitative noncontrast T1 mapping provided independent

  17. 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

  18. Haemodynamic correlates and prognostic significance of serum uric acid in adult patients with Eisenmenger syndrome

    PubMed Central

    Oya, H; Nagaya, N; Satoh, T; Sakamaki, F; Kyotani, S; Fujita, M; Nakanishi, N; Miyatake, K

    2000-01-01

    OBJECTIVE—To assess haemodynamic correlates and prognostic significance of serum uric acid in adult patients with Eisenmenger syndrome.
DESIGN—Retrospective observational study.
SETTING—Tertiary referral centre.
PATIENTS—94 adult patients with Eisenmenger syndrome who were diagnosed between September 1982 and July 1998.
MAIN OUTCOME MEASURES—Serum uric acid was measured in all patients, together with clinical and haemodynamic variables related to mortality.
RESULTS—Serum uric acid was raised in patients with Eisenmenger syndrome compared with age and sex matched control subjects (7.0 v 4.7 mg/dl, p < 0.0001) and increased in proportion to the severity of New York Heart Association functional class. Serum uric acid was positively correlated with mean pulmonary arterial pressure (r = 0.30, p = 0.0052) and total pulmonary resistance index (r = 0.55, p < 0.0001), and negatively correlated with cardiac index (r = −0.50, p < 0.0001). During a mean follow up period of 97 months, 38 patients died of cardiopulmonary causes. Among various clinical, echocardiographic, and laboratory variables, serum uric acid remained predictive in multivariate analysis. Kaplan-Meier survival curves based on median serum uric acid showed that patients with high values had a significantly worse survival rate than those with low values (log-lank test: p = 0.0014 in male patients, p = 0.0034 in female patients).
CONCLUSIONS—Serum uric acid increases in proportion to haemodynamic severity in adult patients with Eisenmenger syndrome and is independently associated with long term mortality.


Keywords: Eisenmenger syndrome; prognosis; uric acid; haemodynamics PMID:10862589

  19. Prognostic significance of SATB1 in gastrointestinal cancer: a meta-analysis and literature review

    PubMed Central

    Zhang, Sheng; Tong, Yi Xin; Xu, Xiang Shang; Lin, Hui; Chao, Teng Fei

    2017-01-01

    Background The special AT-rich sequence-binding proteins 1 (SATB1) is a major regulator involved in cell differentiation. It has been shown that SATB1 acts as an oncogenic regulator. The clinical and prognostic significance of SATB1 in gastrointestinal cancer remains controversial. The purpose of this study is to conduct a systematic review and meta-analysis to elucidate the impact of SATB1 in gastrointestinal cancer. Results A total of 3174 gastrointestinal cancer patients from 15 studies were included. The correlation between SATB1 expression and OS or RFS was investigated in 12 and 5 studies respectively. The results of meta-analysis showed that SATB1 overexpression is inversely correlated with OS (combined HR: 1.79, p = 0.0003) and RFS (combined HR: 2.46, p < 0.0001). In subgroup analysis, SATB1 expression is significantly correlated with poor prognosis in gastrointestinal cancer in Asian population. SATB1 expression is associated with stage, invasion depth, lymph node metastasis and distant metastasis. Methodology Published studies with data on overall survival (OS) and/or relapse free survival (RFS) and SATB1 expression were searched from Cochrane Library, PubMed and Embase (up to Dec 30, 2016). The outcome measurement is hazard ratio (HR) for OS or RFS related with SATB1 expression. Two reviewers independently screened the literatures, extracted the data and performed meta-analysis using RevMan 5.3.0 software. The combined HRs were calculated by fixed- or random-effect models. Conclusions The results of this meta-analysis suggest that SATB1 overexpression is related to advanced stage, lymph node metastasis and distant metastasis. SATB1 overexpression is a marker indicating poor prognosis in gastrointestinal cancer. PMID:28430598

  20. Clinical significance and prognostic value of Nek2 protein expression in colon cancer.

    PubMed

    Lu, Lei; Zhai, Xiaofeng; Yuan, Ronghua

    2015-01-01

    To determine the expression of NIMA-related kinase NEK2 and evaluate its clinical value in colon cancer. Sixty specimens of colon cancer, 30 specimens of paracancerous colon tissues and 10 specimens of normal colon tissues conventionally resected in surgery at the Second Affiliated Hospital of Nantong University from February 2006 to February 2014 were collected. These tissues were detected for the expression of Nek2 using Western Blot and immunohistochemical staining. The relationship between Nek2 protein expression and the clinicopathology and prognosis of colon tissues was discussed. The expression level and positive expression rate of Nek2 protein in the colon cancer were obviously higher than that in the paracancerous tissues and normal colon tissues. They were also significantly higher in the paracancerous tissues than in the normal tissues (P<0.05). Statistical analysis revealed that Nek2 protein expression was not obviously correlated with gender, age and tumor size, but obviously correlated with degree of differentiation (P=0.008), TNM staging (P=0.000), lymph node metastasis (P=0.022) and tumor invasion (P=0.011). With the plotting of Kaplan-Meier survival curve, it could be seen that Nek2 protein expression was not significantly correlated with survival (P=0.0048). High Nek2 protein expression may be an independent risk factor for colon cancer (HR=0.227, 95% CI 0.101-0.510). High Nek2 protein expression reflects the malignant behavior of colon cancer. Playing important roles in the occurrence of colon cancer, Nek2 protein expression has diagnostic and prognostic value in colon cancer.

  1. Clinical significance and prognostic value of Nek2 protein expression in colon cancer

    PubMed Central

    Lu, Lei; Zhai, Xiaofeng; Yuan, Ronghua

    2015-01-01

    Objective: To determine the expression of NIMA-related kinase NEK2 and evaluate its clinical value in colon cancer. Method: Sixty specimens of colon cancer, 30 specimens of paracancerous colon tissues and 10 specimens of normal colon tissues conventionally resected in surgery at the Second Affiliated Hospital of Nantong University from February 2006 to February 2014 were collected. These tissues were detected for the expression of Nek2 using Western Blot and immunohistochemical staining. The relationship between Nek2 protein expression and the clinicopathology and prognosis of colon tissues was discussed. Results: The expression level and positive expression rate of Nek2 protein in the colon cancer were obviously higher than that in the paracancerous tissues and normal colon tissues. They were also significantly higher in the paracancerous tissues than in the normal tissues (P<0.05). Statistical analysis revealed that Nek2 protein expression was not obviously correlated with gender, age and tumor size, but obviously correlated with degree of differentiation (P=0.008), TNM staging (P=0.000), lymph node metastasis (P=0.022) and tumor invasion (P=0.011). With the plotting of Kaplan-Meier survival curve, it could be seen that Nek2 protein expression was not significantly correlated with survival (P=0.0048). High Nek2 protein expression may be an independent risk factor for colon cancer (HR=0.227, 95% CI 0.101-0.510). Conclusion: High Nek2 protein expression reflects the malignant behavior of colon cancer. Playing important roles in the occurrence of colon cancer, Nek2 protein expression has diagnostic and prognostic value in colon cancer. PMID:26823916

  2. Prognostic Significance of Preoperative Prognostic Nutritional Index in Epithelial Ovarian Cancer Patients Treated with Platinum-Based Chemotherapy.

    PubMed

    Miao, Yi; Li, Shuangdi; Yan, Qin; Li, Bilan; Feng, Youji

    2016-01-01

    The aim of present study was to investigate the role of the prognostic nutritional index (PNI) used as a prognostic marker for predicting response and survival outcomes in patients with epithelial ovarian cancer (EOC) who are receiving platinum-based chemotherapy. Patients with a new diagnosis of EOC receiving postoperative platinum-based chemotherapy were identified. The PNI was calculated as 10 × serum albumin value (g/dl) + 0.005 × peripheral lymphocyte count (per mm3). Patients were divided into a platinum-resistant (P-R) group and a platinum-sensitive (P-S) group according to the chemotherapeutic response. A receiver operating characteristic (ROC) curve was used to calculate the optimal cut-off value for PNI to predict chemotherapeutic response and prognosis. A total of 344 patients were enrolled. Area under the curve, sensitivity, and specificity of PIN < 45 to predict platinum resistance were: 0.688, 62.50%, and 83.47%, respectively. Patients with a lower PNI (< 45) had shorter progression-free survival (PFS) and overall survival (OS). PNI showed a significant association with PFS (hazard ratio (HR) 1.890, 95% confidence interval (CI) 1.396-2.560; p < 0.001) and OS (HR 1.747, 95% CI 1.293-2.360; p < 0.001). Our results suggest that PNI assessment could assist the identification of patients with a poor prognosis and has potential clinical value in predicting platinum resistance in patients with EOC. © 2016 S. Karger GmbH, Freiburg.

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

    PubMed

    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

    2015-09-29

    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.

  4. 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

  5. Tumour budding is a strong and independent prognostic factor in pancreatic cancer.

    PubMed

    Karamitopoulou, E; Zlobec, I; Born, D; Kondi-Pafiti, A; Lykoudis, P; Mellou, A; Gennatas, K; Gloor, B; Lugli, A

    2013-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer that escapes detection and resists treatment. Tumour budding, defined as the presence of de-differentiated single tumour cells or small cell clusters at the invasive front of gastrointestinal carcinomas like colorectal, oesophageal, gastric and ampullary, is linked to adverse prognosis. Tumour budding has not yet been reported in PDAC. To assess the frequency and prognostic impact of tumour budding in PDAC. Whole-tissue sections of 117 PDACs with full clinico-pathological and follow-up information, including postoperative therapy, were stained using a pancytokeratin marker. Tumour budding was assessed in 10 high-power fields (HPFs) by two pathologists. High-grade budding was defined as an average of >10buds across 10HPFs. Measurements were correlated to patient and tumour characteristics. The study was performed according to the REMARK guidelines. Inter-observer agreement was considered strong (ICC=0.72). Low-grade budding was observed in 29.7% and high-grade budding in 70.3% cases. High-grade budding was linked to advanced pT classification (p=0.0463), lymphatic invasion (p=0.0192) and decreased disease-free (p=0.0005) and overall survival (p<0.0001). There was no association with pN, pM, R-status or blood vessel invasion. In multivariate analysis, the prognostic effect of tumour budding was independent of lymph node metastasis, lymphatic invasion and R-status (p<0.0001; HR (95% CI): 3.65 (2.1-6.4)). Our results show that high-grade tumour budding occurs frequently in PDAC and is a strong, independent and reproducible, highly unfavourable prognostic factor that could be used to guide future individualised therapeutic approaches. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. [What is the prognostic significance of histomorphology in small cell lung carcinoma?].

    PubMed

    Facilone, F; Cimmino, A; Assennato, G; Sardelli, P; Colucci, G A; Resta, L

    1993-01-01

    What is the prognostic significant of the histomorphology in the small cell carcinomas of the lung? After the WHO classification of the lung cancer (1981), several studies criticized the subdivision of the small cell carcinoma in three sub-types (oat-cell, intermediate cell and combined types). The role of histology in the prognostic predition has been devaluated. In order to verify the prognostic value of the morphology of the small cell types of lung cancer, we performed a multivariate analysis in 62 patients. The survival rate was analytically compared with the following parameters: nuclear maximum diameter, nuclear form, nuclear chromatism, chromatine distribution, presence of nucleolus, evidence of cytoplasm. The results showed that none of these parameters are able to express a prognostic value. According to the recent studies, we think that the small cell carcinoma of the lung is a neoplasia with a multiform histologic pattern. Differences observed in clinical management are not correlate with the morphology, but with other biological parameters still unknown.

  7. Prognostic significance of tumour markers in Chinese patients with gastric cancer.

    PubMed

    Liu, Xiaowen; Cai, Hong; Wang, Yanong

    2014-06-01

    The clinical value of preoperative tumour markers remains elusive in gastric cancer. The aim of this study was to investigate the prognostic value of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, CA50 and CA72-4 in gastric cancer. About 391 gastric cancer patients who underwent curative D2 gastrectomy between 2001 and 2006 were evaluated. The correlation between tumour markers and clinicopathologic characteristics and prognostic value of preoperative tumour markers was investigated. Correlation analysis showed that AFP was associated with tumour size (P = 0.040); CEA with lymphatic invasion (P = 0.023) and pathological stage (P = 0.018); CA19-9 with tumour size (P = 0.000), Borrmann type (P = 0.027), lymphatic invasion (P = 0.020) and pathological stage (P = 0.001); CA50 with lymphatic invasion (P = 0.004) and pathological stage (P = 0.004); CA72-4 with tumour size (P = 0.000), tumour size (P = 0.000) and Borrmann type (P = 0.008); lymphatic invasion (P = 0.000), nervous invasion (P = 0.028) and pathological stage (P = 0.000). Multivariate analysis showed that CEA, tumour site, Borrmann type and pathological stage were independent prognostic factors. Preoperative CEA might be a candidate for the staging system in addition to conventional factors. © 2012 The Authors. ANZ Journal of Surgery © 2012 Royal Australasian College of Surgeons.

  8. Diagnostic and prognostic significance of lysophosphatidic acid in malignant pleural effusions

    PubMed Central

    Bai, Cui-Qing; Yao, Yan-Wen; Liu, Chun-Hua; Zhang, He; Xu, Xiao-Bing; Zeng, Jun-Li; Liang, Wen-Jun; Yang, Wen

    2014-01-01

    Background Lysophosphatidic acid (LPA) is an important extracellular signal transmitter and intracellular second messenger in body fluids. It can be detected in the ascitic fluid of patients with ovarian cancer. Increasing evidence shows that LPA can stimulate cancer cell proliferation and promote tumor invasion and metastasis. Our study aimed to evaluate the diagnostic value of LPA in differentiating between malignant pleural effusions (MPEs) and benign pleural effusions (BPEs) and to evaluate the association between the level of LPA in MPE and the prognosis of lung cancer patients. Patients and methods The level of LPA in the pleural effusions (PEs) of 123 patients (94 MPE, 29 BPE) with lung cancer was evaluated using an enzyme-linked immunosorbent assay. The performance of LPA was analyzed by standard Receiver operator characteristic curve (ROC) analysis methods, using the area under the curve (AUC) as a measure of accuracy. Overall survival (OS) curves and progression-free survival (PFS) curves were based on the Kaplan-Meier method, and the survival differences between subgroups were analyzed using the log-rank or Breslow test (SPSS software). A multivariate Cox proportional hazards model was used to assess whether LPA independently predicted lung cancer survival. Results The levels of LPA differed significantly between MPE (22.08±8.72 µg/L) and BPE (14.61±5.12 µg/L) (P<0.05). Using a cutoff point of 18.93 µg/L, LPA had a sensitivity of 60% and a specificity of 83% to distinguish MPEs from BPEs with an AUC of 0.769±0.045 (SE) (P=0.000) (95% CI, 0.68-0.857). In the three pathological types of lung cancer patients with MPE, there were no significant associations between LPA levels and the length of PFS and OS (P=0.58 and 0.186, respectively). Interestingly, in the patients with MPE caused by lung adenocarcinoma there were significant associations between the LPA levels and the PFS and OS (P=0.018 and 0.026, respectively). Multivariate analysis showed that

  9. Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma: Tumor-Infiltrating CD10+ Neutrophil/CD20+ Lymphocyte Ratio as an Independent Prognostic Factor

    PubMed Central

    Kadota, Kyuichi; Nitadori, Jun-ichi; Ujiie, Hideki; Buitrago, Daniel H.; Woo, Kaitlin M.; Sima, Camelia S.; Travis, William D.; Jones, David R.; Adusumilli, Prasad S.

    2015-01-01

    Introduction We previously reported the prognostic significance of the lung adenocarcinoma immune microenvironment. In this study, we preformed comprehensive analysis of immune markers and their associations with prognosis in patients with lung squamous cell carcinoma. Methods We reviewed surgically resected, solitary lung squamous cell carcinoma patients (n = 485; 1999 to 2009) that were randomly split into a training cohort (n = 331) and validation cohort (n = 154). We constructed tissue microarrays and performed immunostaining for CD3, CD45RO, CD8, CD4, FoxP3, CD20, CD68, CXCL12, CXCR4, CCR7, IL-7R, and IL-12Rβ2. Overall survival (OS) was analyzed using the log-rank test and the Cox proportional hazards model. Results Analysis of single immune cell infiltration revealed that high tumor-infiltrating CD10+ neutrophils were associated with worse prognoses in the training cohort (P = 0.021). Analysis of biologically relevant immune cell combinations identified that patients with high CD10+ neutrophil and low CD20+ lymphocyte had a significantly worse OS (5-year OS, 42%) than those with other combinations of CD10 and CD20 (5-year OS, 62%; P < 0.001); this was confirmed in the validation cohort (P = 0.032). For the multivariate analysis, high CD10/low CD20 immune cell infiltration was an independent predictor of OS in both the training cohort (HR = 1.61, P = 0.006) and validation cohort (HR = 1.75; P = 0.043). Conclusions High CD10+/low CD20+ immune cell infiltration ratio is a significant prognostic factor of lung squamous cell carcinoma. Immunomodulatory therapy of tumor-specific neutrophil and B lymphocyte responses may have applicability in the treatment of lung squamous cell carcinoma. PMID:26291010

  10. Preoperative lymphocyte count is an independent prognostic factor in node-negative non-small cell lung cancer.

    PubMed

    Kobayashi, Naohiro; Usui, Shingo; Kikuchi, Shinji; Goto, Yukinobu; Sakai, Mitsuaki; Onizuka, Masataka; Sato, Yukio

    2012-02-01

    A number of prognostic factors have been reported in non-small cell lung cancer (NSCLC). Although lymph node metastasis is the most poorly predictive value in completely resected NSCLC, a significant number of patients have a fatal recurrence even in node-negative curative NSCLC. Recently inflammatory response has been shown as a predictive value in NSCLC. Neutrophils and lymphocytes play an important role in cancer immune response. In this study, we retrospectively examined the impact of preoperative peripheral neutrophil and lymphocyte counts on survival, and investigated the relationships of these factors to clinicopathological factors in node-negative NSCLC. A total 237 patients were evaluated. When the cut-off value of neutrophil count was 4500 mm(-3) with a maximum log-rank statistical value, overall 5-year survival rates were 79.7% for the low-neutrophil-count group and 69.5% for the high-neutrophil-count group (P=0.04). When the cut-off value of lymphocyte count was 1900 mm(-3) with a maximum log-rank statistical value, overall survival rates were 67.9% for the low-lymphocyte group and 87.7% for the high-lymphocyte group (P<0.001). High-neutrophil-counts were associated with tumor size (P=0.002) and pleural invasion (P<0.001). Low-lymphocyte-counts were correlated with vascular invasion (P=0.018) and recurrence of NSCLC (P=0.01). Multivariate analysis showed that the lymphocyte count was an independent prognostic factor (hazard ratio: 3.842; 95% confidence interval: 1.827-8.078; P<0.001), but the neutrophil count was not (P=0.185). We conclude that a peripheral lymphocyte count, which is associated with vascular invasion, is an independent prognostic factor in node-negative NCSLC.

  11. Expression of E-cadherin in oesophageal carcinomas from the UK and China: disparities in prognostic significance.

    PubMed Central

    Jian, W G; Darnton, S J; Jenner, K; Billingham, L J; Matthews, H R

    1997-01-01

    AIMS: To study the expression and prognostic significance of the cell adhesion molecule E-cadherin in oesophageal tumours from the UK (low risk area) and China (high risk area). METHODS: E-cadherin expression was measured immunohistochemically in resected tumours from 17 patients in the UK with adenocarcinoma, 23 patients from the UK with squamous carcinoma, and 30 patients from China with squamous carcinomas who survived for five years postoperatively and compared with similar tumours from patients in the same regions who did not survive (140 tumours in all). RESULTS: Normal squamous epithelial cells and well differentiated areas of tumours showed membranous staining for E-cadherin expression. Cytoplasmic staining, heterogeneous staining, or an absence of staining was seen in dysplastic epithelium and in less well differentiated areas of tumours. Only one of 140 primary tumours had homogeneous membranous expression. In tumours from UK patients with adenocarcinoma (p = 1.00) and from Chinese patients with squamous carcinomas (p = 0.06) there was no correlation between E-cadherin absence and non-survival. In tumours from UK patients with squamous carcinomas there was a significant correlation between absence of E-cadherin and non-survival (p = 0.009). Tumours from UK patients with squamous carcinoma who survived were significantly less likely to be E-cadherin absent than those from Chinese patients with squamous carcinomas who survived (p = 0.007). Multivariate analysis (n = 37 UK, paired data) showed that absence of E-cadherin in the primary tumour was a weak independent prognostic factor for non-survival (30% significance level; p = 0.26; odds ratio = 3.56). In UK nodal metastases there was no correlation between E-cadherin expression and survival. CONCLUSIONS: Squamous carcinomas from UK patients differed from both adenocarcinomas from UK patients and carcinomas from Chinese patients with respect to E-cadherin expression and prognostic significance. In tumours

  12. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

    PubMed Central

    Che, Keying; Zhao, Yang; Qu, Xiao; Pang, Zhaofei; Ni, Yang; Zhang, Tiehong; Du, Jiajun; Shen, Hongchang

    2017-01-01

    Purpose Gastric carcinoma (GC) is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma. Materials and methods Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS) was statistically analyzed. Results Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145) of them. Single cell invasion and large cell invasion were observed in 62.8% (186) and 16.9% (50) of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0.001). Similarly, the OS of patients with single cell invasion and large cell invasion was reduced (single cell invasion, HR: 3.553, P<0.001; large cell invasion, HR: 2.466, P<0.001). Following multivariate analysis, tumor budding and single cell invasion were observed to be independent risk factors for gastric adenocarcinoma (P<0.05). According to the Lauren classification, patients with intestinal-type adenocarcinoma had better outcomes than those with diffuse-type adenocarcinoma (HR: 2.563, P<0.001). Conclusion Tumor budding and single cell invasion in gastric adenocarcinoma are associated with an unfavorable prognosis. PMID:28255247

  13. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.

    PubMed

    Che, Keying; Zhao, Yang; Qu, Xiao; Pang, Zhaofei; Ni, Yang; Zhang, Tiehong; Du, Jiajun; Shen, Hongchang

    2017-01-01

    Gastric carcinoma (GC) is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma. Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS) was statistically analyzed. Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145) of them. Single cell invasion and large cell invasion were observed in 62.8% (186) and 16.9% (50) of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0.001). Similarly, the OS of patients with single cell invasion and large cell invasion was reduced (single cell invasion, HR: 3.553, P<0.001; large cell invasion, HR: 2.466, P<0.001). Following multivariate analysis, tumor budding and single cell invasion were observed to be independent risk factors for gastric adenocarcinoma (P<0.05). According to the Lauren classification, patients with intestinal-type adenocarcinoma had better outcomes than those with diffuse-type adenocarcinoma (HR: 2.563, P<0.001). Tumor budding and single cell invasion in gastric adenocarcinoma are associated with an unfavorable prognosis.

  14. Prognostic significance of urokinase (uPA) and its inhibitor PAI-1 for survival in advanced ovarian carcinoma stage FIGO IIIc.

    PubMed

    Kuhn, W; Schmalfeldt, B; Reuning, U; Pache, L; Berger, U; Ulm, K; Harbeck, N; Späthe, K; Dettmar, P; Höfler, H; Jänicke, F; Schmitt, M; Graeff, H

    1999-04-01

    Strong evidence has accumulated on the prognostic value of tumour-associated proteolytic factors in patients afflicted with solid malignant tumours, including advanced ovarian cancer. We evaluated the prognostic impact of the protease urokinase plasminogen activator (uPA) and its inhibitor PAI-1 on overall survival in patients with advanced ovarian cancer stage FIGO IIIc in order to select patients at risk. uPA and PAI-1 antigen were determined by ELISA in primary tumour tissue extracts of 86 ovarian cancer patients FIGO stage IIIc enrolled in a prospective study. Univariate and multivariate analyses were performed using the Cox proportional hazard model. The time-varying coefficient model of Gray was used to assess the time-dependent strength of prognostic factors tumour mass, uPA and PAI-1 on overall survival. In all patients, uPA and PAI-1 (optimized cut-offs of 2.0 and 27.5 ng mg(-1) protein respectively), in addition to the traditional prognostic parameters of residual tumour mass, nodal status, grading and ascites volume, were of prognostic significance in univariate analysis for overall survival. Even in patients with residual tumour mass (n = 43), the statistically independent prognostic impact of PAI-1 persisted, allowing further discrimination between low- and high-risk patients. In multivariate analysis, residual tumour mass (P < 0.001, relative risk (RR) 4.5), PAI-1 (P < 0.001; RR 3.1) and nodal status (P = 0.022, RR 2.6) turned out to be strong, statistically independent prognostic parameters. Evaluation of the time-dependent prognostic impact of residual tumour mass and PAI-1 on overall survival (n = 86, 50 months) revealed that the prognostic power of these factors increased with time. In patients with advanced ovarian cancer, both residual tumour mass and PAI-1 are statistically independent strong prognostic factors. Even within patient subgroups with or without residual tumour mass, PAI-1 allowed selection of patients at risk who might benefit from

  15. Prognostic significance of baseline metabolic tumor volume in relapsed and refractory Hodgkin lymphoma.

    PubMed

    Moskowitz, Alison J; Schöder, Heiko; Gavane, Somali; Thoren, Katie L; Fleisher, Martin; Yahalom, Joachim; McCall, Susan J; Cadzin, Briana R; Fox, Stephanie Y; Gerecitano, John; Grewal, Ravinder; Hamlin, Paul A; Horwitz, Steven M; Kumar, Anita; Matasar, Matthew; Ni, Andy; Noy, Ariela; Palomba, M Lia; Perales, Miguel-Angel; Portlock, Carol S; Sauter, Craig; Straus, David; Younes, Anas; Zelenetz, Andrew D; Moskowitz, Craig H

    2017-09-05

    Identification of prognostic factors for patients with relapsed or refractory (rel/ref) Hodgkin lymphoma (HL) is essential for optimizing therapy with risk-adapted approaches. In our phase II study of PET-adapted salvage therapy with brentuximab vedotin (BV) and augmented ifosfamide, carboplatin, etoposide (augICE) we assessed clinical factors, quantitative PET assessments, and cytokines/chemokine values. Transplant-eligible patients with rel/ref HL received 2 (cohort 1) or 3 (cohort 2) cycles of weekly BV; PET-negative (Deauville ≤ 2) patients proceeded to autologous stem cell transplant (ASCT) while PET-positive patients received augICE before ASCT. Serum cytokine and chemokine levels were measured at baseline and after BV. Metabolic tumor volume (MTV) and total lesion glycolysis were measured at baseline, after BV and after augICE. 65 patients enrolled (45 cohort 1, 20 cohort 2); 49 (75%) achieved CR and 64 proceeded to ASCT. 3-year overall survival and EFS were 95% and 82%. Factors predictive for EFS by multivariate analysis were baseline MTV (bMTV) (p<0.001) and refractory disease (p=0.003). Low bMTV (<109.5cm(3)) and relapsed disease identified a favorable group (3-yr EFS 100%). For transplanted patients, bMTV and pre-ASCT PET were independently prognostic; 3-year EFS for pre-ASCT PET-positive patients with low bMTV was 86%. In this phase II study of PET-adapted therapy with BV and augICE for rel/ref HL, bMTV and refractory disease were independent prognostic factors for EFS. Furthermore, bMTV improved the predictive power of pre-ASCT PET. Future studies should optimize efficacy and tolerability of salvage therapy by stratifying patients according to risk factors such as bMTV. Copyright © 2017 American Society of Hematology.

  16. CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900

    PubMed Central

    Gönen, Mithat; Sun, Zhuoxin; Figueroa, Maria E.; Patel, Jay P.; Abdel-Wahab, Omar; Racevskis, Janis; Ketterling, Rhett P.; Fernandez, Hugo; Rowe, Jacob M.; Tallman, Martin S.; Melnick, Ari; Levine, Ross L.

    2012-01-01

    We determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25POS myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25POS patients had inferior complete remission rates (P = .0005) and overall survival (P < .0001) compared with CD25NEG cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of FLT3-ITDPOS AML was restricted to CD25POS patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25POS status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25POS status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML. PMID:22855599

  17. Clinicopathological and prognostic significance of platelet to lymphocyte ratio in patients with gastric cancer

    PubMed Central

    Gu, Xiaobin; Gao, Xian-Shu; Cui, Ming; Xie, Mu; Peng, Chuan; Bai, Yun; Guo, Wei; Han, Linjun; Gu, Xiaodong; Xiong, Wei

    2016-01-01

    The present study was aim to investigate the prognostic role of platelet to lymphocyte ratio (PLR) for patients with gastric cancer (GC) using meta-analysis. A total of 13 studies (14 cohorts) with 6,280 subjects were included. By pooling hazard ratios (HRs) and 95% confidence intervals (CIs) and odds ratios (ORs) and 95% CIs from each study, we found that elevated PLR was significantly associated with poorer overall survival (OS) (HR: 1.3, 95% CI: 1.1–1.52, p = 0.001; I2 = 68.5%, Ph < 0.001) but not with poor disease-free survival (DFS) (HR: 1.6, 95% CI: 0.88–2.9, p = 0.122; I2 = 87.8%, Ph < 0.001). Subgroup analysis showed that a high PLR significantly predicted poor OS in Caucasian populations, patients receiving chemotherapy and patients at advanced stage. In addition, the cut-off value of PLR > 160 showed adequately prognostic value. Furthermore, elevated PLR was associated with lymph node metastasis and CEA levels in GC. Our meta-analysis showed that elevated PLR could be a significant prognostic biomarker for poor OS in patients with GC. PMID:27409665

  18. 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.

  19. The prognostic significance of surgical staging for carcinoma of the endometrium.

    PubMed

    Wolfson, A H; Sightler, S E; Markoe, A M; Schwade, J G; Averette, H E; Ganjei, P; Hilsenbeck, S G

    1992-05-01

    surgical Stage IA (93.8% 5 YS) or IB (95.4% 5 years). In summary, this study demonstrates that surgical staging as recommended by FIGO is indicated to accurately determine the initial extent of disease in endometrial carcinoma. In addition, surgical staging is the strongest predictor of survival. Deep myometrial invasion appears to be a significant independent prognostic factor within surgical Stage I. The role of adjunctive radiotherapy in Stage I disease awaits the results from an ongoing multi-institutional, prospectively randomized trial.

  20. Prognostic significance of body mass index in Asian patients with localized renal cell carcinoma.

    PubMed

    Komura, Kazumasa; Inamoto, Teruo; Black, Peter C; Koyama, Kohei; Katsuoka, Yoji; Watsuji, Toshikazu; Azuma, Haruhito

    2011-01-01

    We investigated the prognostic value of BMI (body mass index) in Asian patients with RCC (renal cell carcinoma). We evaluated 170 Asian patients who underwent surgery for localized RCC (pathologic T1-4 tumors in the absence of nodal or distant metastases) between 1996 and 2004 at our institution. Patients were stratified by BMI: 22 or less vs. greater than 22. Overall, CSS (cancer-specific survival) and RFS (recurrence-free survival) was estimated using the Kaplan-Meier method. Multivariate analysis was performed with the Cox regression model. The mean age and BMI of all patients was 62.4 ± 11.4 yr and 23.1 ± 3.2 kg/m(2), respectively. Patients' population consisted of 114 (67.1%) men and 56 (32.9%) women. The median follow-up was 50 mo. The BMI was less than 22 in 83 (49%) patients and greater than 22 in 87 (51%). There was a trend toward worse Eastern Cooperative Oncology Group (ECOG) performance status, less likely to have an incidentaloma, higher pathological stage, and more frequent microvascular invasion with lower BMI. Only the correlations between BMI and ECOG performance status (P = 0.003) and pathological stage (P = 0.015) were statistically significant. Of other relevant factors including gender, mode of presentation, ECOG performance status, C-reactive protein, histological type, Fuhrman nuclear grade, microvascular invasion, pathological stage, and adjuvant cytokine therapy, smaller BMI remained an independent predictor for worse CSS (44.5 mo vs. 56.0 mo, P = 0.041, HR = 10.99) and RFS (43.0 mo vs. 55.0 mo, P = 0.03, HR = 2.653), but not for OS (overall survival) (46.0 mo vs. 55.5 mo, P = 0.13, HR = 2.217) on multivariate analysis. Our findings identify increasing BMI in the Asian population as an independent predictor for favorable CSS and RFS in patients with RCC treated by surgery. Further studies, including a multiinstitutional, prospective Asian cohort, are required to confirm these findings.

  1. 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

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

    PubMed

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

    2016-06-01

    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.

  3. Independent and incremental prognostic value of novel cardiac biomarkers in chronic hemodialysis patients.

    PubMed

    Obokata, Masaru; Sunaga, Hiroaki; Ishida, Hideki; Ito, Kyoko; Ogawa, Tetsuya; Ando, Yoshitaka; Kurabayashi, Masahiko; Negishi, Kazuaki

    2016-09-01

    End-stage renal disease is a major clinical and public health problem, and cardiovascular disease accounts for half of the mortality in hemodialysis patients. An existing mortality risk score (AROii score) or N-terminal pro-brain natriuretic peptide (NT-proBNP) level have modest predictive power, but there is room for improvement. There are emerging cardiac biomarkers (soluble isoforms of ST2 [sST2], galectin-3 [Gal-3]), and uremic toxicity (indoxyl sulfate). We sought to determine whether these biomarkers predict cardiovascular outcomes in hemodialysis patients and have incremental prognostic value over the clinical score and NT-proBNP level. A total of 423 hemodialysis patients were prospectively followed up for primary (all-cause death) and secondary end points (a composite of all-cause death or cerebrocardiovascular events). During a mean follow-up of 2.1 ± 0.4 years, there were 48 all-cause deaths and 78 composite outcomes. Soluble isoforms of ST2, Gal-3, and NT-proBNP were associated with all-cause deaths but indoxyl sulfate was not in both log-rank test and receiver operating characteristic analysis. Both sST2 and Gal-3 had independent and incremental prognostic value for both outcomes over the AROii score and NT-proBNP. Although adding sST2 did not reclassify over the model-based AROii score and NT-proBNP for all-cause death, further addition of Gal-3 did. Subgroup analyses of patients with left ventricular ejection fraction measurement (n = 301) corroborated these results, where the 2 biomarkers remained independent and incremental for both all-cause death and composite outcome after adjusting for the risk score and the ejection fraction. Both sST2 and Gal-3 had independent and incremental prognostic values over NT-proBNP and an established risk score in patients with hemodialysis. Assessment of sST2 and Gal-3 further enhances risk stratification. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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

  5. Prognostic significance of immunohistochemical classification of diffuse large B-cell lymphoma.

    PubMed

    Alacacioglu, Inci; Ozcan, Mehmet Ali; Ozkal, Sermin; Piskin, Ozden; Turgut, Nurhilal; Demirkan, Fatih; Ozsan, Guner Hayri; Kargi, Aydanur; Undar, Bulent

    2009-04-01

    To evaluate the clinical significance of immunoperoxidase staining for CD10, bcl-6, mum-1 and bcl-2 to subdivide DLBCL into prognostic subgroups, we analysed 50 DLBCL cases using immunohistochemical methods. Fifty DLBCL patients were evaluated retrospectively. The expression of CD10 was associated with better OS (p=0.04) whereas expression of mum-1 was associated with worse OS (p=0.009). There were no significance of OS in case of expression of bcl-6 (p=0.05) and bcl-2 (p=0.3). They were subclassified using CD10, mum-1, bcl-6 as germinal center B-cell like (GCB) lymphoma (30%) and non-GCB lymphoma (70%). The OS and EFS (event free survival) were longer in GCB group (p=0.002) and 5-year OS for GCB group was 92% compared with only 44% for the non-GCB group (p=0.02). The OS of the GCB group also was longer compared to that of the non-GCB group in low IPI subgroup (p=0.01). The existence of survival differences between GCB a non-GCB group also in the patients with low IPI score, showed the importance of prognostic classification in the risk-adaptive treatment approaches. The classification as GCB and non-GCB based immunostains may enable to define more accurate prognostic groups in DLBCL.

  6. Prognostic significance and function of the vacuolar H+-ATPase subunit V1E1 in esophageal squamous cell carcinoma.

    PubMed

    Son, Sung Wook; Kim, Seok-Hyung; Moon, Eun-Yi; Kim, Dong-Hoon; Pyo, Suhkneung; Um, Sung Hee

    2016-08-02

    Vacuolar H+-ATPase (V-ATPase), a hetero-multimeric ATP-driven proton pump has recently emerged as a critical regulator of mTOR-induced amino acid sensing for cell growth. Although dysregulated activity of cell growth regulators is often associated with cancer, the prognostic significance and metabolic roles of V-ATPase in esophageal cancer progression remain unclear. Here, we show that high levels of V-ATPase subunit V1E1 (V-ATPase V1E1) were significantly associated with shortened disease-free survival in patients with esophageal squamous cell carcinoma (ESCC). Multivariate analysis identified the V-ATPase V1E1 as an independent adverse prognostic factor (hazard ratio;1.748, P = 0.018). In addition, depletion of V-ATPase V1E1 resulted in reduced cell motility, decreased glucose uptake, diminished levels of lactate, and decreased ATP production, as well as inhibition of glycolytic enzyme expression in TE8 esophageal cancer cells. Consistent with these results, the Cancer Genome Atlas (TCGA) data and Gene Set Enrichment Analysis (GSEA) showed a high frequency of copy number alterations of the V-ATPase V1E1 gene, and identified a correlation between levels of V-ATPase V1E1 mRNA and Pyruvate Kinase M2 (PKM2) in ESCC. High expression levels of both V-ATPase V1E1 and phosphorylated PKM2 (p-PKM2), a key player in cancer metabolism, were associated with poorer prognosis in ESCC. Collectively, our findings suggest that expression of the V-ATPase V1E1 has prognostic significance in ESCC, and is closely linked to migration, invasion, and aerobic glycolysis in esophageal cancer cells.

  7. Prognostic significance and function of the vacuolar H+-ATPase subunit V1E1 in esophageal squamous cell carcinoma

    PubMed Central

    Kim, Dong-Hoon; Pyo, Suhkneung; Um, Sung Hee

    2016-01-01

    Vacuolar H+-ATPase (V-ATPase), a hetero-multimeric ATP-driven proton pump has recently emerged as a critical regulator of mTOR-induced amino acid sensing for cell growth. Although dysregulated activity of cell growth regulators is often associated with cancer, the prognostic significance and metabolic roles of V-ATPase in esophageal cancer progression remain unclear. Here, we show that high levels of V-ATPase subunit V1E1 (V-ATPase V1E1) were significantly associated with shortened disease-free survival in patients with esophageal squamous cell carcinoma (ESCC). Multivariate analysis identified the V-ATPase V1E1 as an independent adverse prognostic factor (hazard ratio;1.748, P = 0.018). In addition, depletion of V-ATPase V1E1 resulted in reduced cell motility, decreased glucose uptake, diminished levels of lactate, and decreased ATP production, as well as inhibition of glycolytic enzyme expression in TE8 esophageal cancer cells. Consistent with these results, the Cancer Genome Atlas (TCGA) data and Gene Set Enrichment Analysis (GSEA) showed a high frequency of copy number alterations of the V-ATPase V1E1 gene, and identified a correlation between levels of V-ATPase V1E1 mRNA and Pyruvate Kinase M2 (PKM2) in ESCC. High expression levels of both V-ATPase V1E1 and phosphorylated PKM2 (p-PKM2), a key player in cancer metabolism, were associated with poorer prognosis in ESCC. Collectively, our findings suggest that expression of the V-ATPase V1E1 has prognostic significance in ESCC, and is closely linked to migration, invasion, and aerobic glycolysis in esophageal cancer cells. PMID:27384996

  8. Prognostic significance of Doppler-derived left ventricular diastolic filling variables in dilated cardiomyopathy.

    PubMed

    Shen, W F; Tribouilloy, C; Rey, J L; Baudhuin, J J; Boey, S; Dufossé, H; Lesbre, J P

    1992-12-01

    To determine the prognostic significance of pulsed wave Doppler-derived left ventricular diastolic filling velocity profiles and the relationship between Doppler variables and clinical functional status, the follow-up outcomes of 62 consecutive patients with dilated cardiomyopathy and symptoms of left ventricular dysfunction were analyzed. All patients had echocardiographic left ventricular end-diastolic dimension > or = 6.0 cm, fractional shortening < 25%, increased E pointseptal separation, and diffuse hypokinesia or akinesia. During a mean follow-up period of 30.5 +/- 13.9 months, 27 patients experienced cardiac events: 23 died of either progressive pump failure or an episode of sudden death and four required cardiac transplantation because of refractory heart failure. Peak early filling velocity (78 +/- 23 cm/sec vs 65 +/- 25 cm/sec; p < 0.03) was higher and late atrial filing velocity (34 +/- 13 cm/sec vs 55 +/- 19 cm/sec; p < 0.001) was lower in patients with cardiac events than in cardiac event-free survivors. The ratio of early to late transmitral filling velocities was higher (2.6 +/- 1.2 vs 1.5 +/- 1.3; p < 0.001), and the deceleration time of early diastole was shorter (133 +/- 48 msec vs 175 +/- 71 msec; p < 0.001) in patients with cardiac events. The cardiac event rate was significantly higher in patients with an early to late filling velocity ratio greater than 2 (77% vs 19%; p < 0.001) or a deceleration time less than 150 msec (58% vs 23%; p < 0.05) than in those without. Stepwise multivariate regression analysis revealed that the pattern of transmitral early to late filling velocity ratio was the only significant independent Doppler echocardiographic predictor of outcome for these patients. Repeat Doppler echocardiographic examinations, which were performed in 31 survivors after intensive treatment (mean, 38.6 +/- 6.5 months), showed that early filling velocity was decreased (55 +/- 20 cm/sec vs 75 +/- 25 cm/sec; p < 0.02), late atrial filling

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

    PubMed

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

    2016-02-01

    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 (F-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 F-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 F-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 stratification in clinical

  10. 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.

  11. Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

    SciTech Connect

    Hwang, Chung-Feng; Huang, Hsuan-Ying; Chen, Chang-Han; Chien, Chih-Yen; Hsu, Yao-Chung; Li, Chien-Feng; and others

    2012-02-01

    Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median ({>=}60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.

  12. Deletion of 18q is a strong and independent prognostic feature in prostate cancer.

    PubMed

    Kluth, Martina; Graunke, Maximilian; Möller-Koop, Christina; Hube-Magg, Claudia; Minner, Sarah; Michl, Uwe; Graefen, Markus; Huland, Hartwig; Pompe, Raisa; Jacobsen, Frank; Hinsch, Andrea; Wittmer, Corinna; Lebok, Patrick; Steurer, Stefan; Büscheck, Franziska; Clauditz, Till; Wilczak, Waldemar; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald

    2016-12-27

    Deletion of 18q recurrently occurs in prostate cancer. To evaluate its clinical relevance, dual labeling fluorescence in-situ hybridization (FISH) using probes for 18q21 and centromere 18 was performed on a prostate cancer tissue microarray (TMA). An 18q deletion was found in 517 of 6,881 successfully analyzed cancers (7.5%). 18q deletion was linked to unfavorable tumor phenotype. An 18q deletion was seen in 6.4% of 4,360 pT2, 8.0% of 1,559 pT3a and 11.8% of 930 pT3b-pT4 cancers (P < 0.0001). Deletions of 18q were detected in 6.9% of 1,636 Gleason ≤ 3 + 3, 6.8% of 3,804 Gleason 3 + 4, 10.1% of 1,058 Gleason 4+3, and 9.9% of 344 Gleason ≥ 4 + 4 tumors (P = 0.0013). Deletions of 18q were slightly more frequent in ERG-fusion negative (8.2%) than in ERG-fusion positive cancers (6.4%, P = 0.0063). 18q deletions were also linked to biochemical recurrence (BCR, P < 0.0001). This was independent from established pre- and postoperative prognostic factors (P ≤ 0.0004). In summary, the results of our study identify 18q deletion as an independent prognostic parameter in prostate cancer. As it is easy to measure, 18q deletion may be a suitable component for multiparametric molecular prostate cancer prognosis tests.

  13. Deletion of 18q is a strong and independent prognostic feature in prostate cancer

    PubMed Central

    Möller-Koop, Christina; Hube-Magg, Claudia; Minner, Sarah; Michl, Uwe; Graefen, Markus; Huland, Hartwig; Pompe, Raisa; Jacobsen, Frank; Hinsch, Andrea; Wittmer, Corinna; Lebok, Patrick; Steurer, Stefan; Büscheck, Franziska; Clauditz, Till; Wilczak, Waldemar; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald

    2016-01-01

    Deletion of 18q recurrently occurs in prostate cancer. To evaluate its clinical relevance, dual labeling fluorescence in-situ hybridization (FISH) using probes for 18q21 and centromere 18 was performed on a prostate cancer tissue microarray (TMA). An 18q deletion was found in 517 of 6,881 successfully analyzed cancers (7.5%). 18q deletion was linked to unfavorable tumor phenotype. An 18q deletion was seen in 6.4% of 4,360 pT2, 8.0% of 1,559 pT3a and 11.8% of 930 pT3b-pT4 cancers (P < 0.0001). Deletions of 18q were detected in 6.9% of 1,636 Gleason ≤ 3 + 3, 6.8% of 3,804 Gleason 3 + 4, 10.1% of 1,058 Gleason 4+3, and 9.9% of 344 Gleason ≥ 4 + 4 tumors (P = 0.0013). Deletions of 18q were slightly more frequent in ERG-fusion negative (8.2%) than in ERG-fusion positive cancers (6.4%, P = 0.0063). 18q deletions were also linked to biochemical recurrence (BCR, P < 0.0001). This was independent from established pre- and postoperative prognostic factors (P ≤ 0.0004). In summary, the results of our study identify 18q deletion as an independent prognostic parameter in prostate cancer. As it is easy to measure, 18q deletion may be a suitable component for multiparametric molecular prostate cancer prognosis tests. PMID:27861151

  14. Pretreatment prognostic nutritional index is a significant predictor of prognosis in patients with cervical cancer treated with concurrent chemoradiotherapy

    PubMed Central

    Haraga, Junko; Nakamura, Keiichiro; Omichi, Chiaki; Nishida, Takeshi; Haruma, Tomoko; Kusumoto, Tomoyuki; Seki, Noriko; Masuyama, Hisashi; Katayama, Norihisa; Kanazawa, Susumu; Hiramatsu, Yuji

    2016-01-01

    This study investigated whether pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index (PNI) are prognostic factors in patients with cervical cancer who undergo concurrent chemoradiotherapy (CCRT) and radiotherapy (RT). A total of 131 patients who underwent CCRT and RT for cervical cancer were retrospectively investigated and the correlations of NLR, PLR and PNI with clinical parameters and prognosis were assessed in CCRT and RT. The CCRT and RT groups had a median progression-free survival (PFS) of 41.82 and 24.72 months, respectively, and an overall survival of 49.70 and 29.56 months, respectively. At a cut-off value of NLR≥2.85, the PFS and OS in patients with higher NLR undergoing RT were significantly shorter compared with those in patients with lower NLR (P=0.029 and P=0.017, respectively). At a cut-off value for PNI of ≤48.55 in patients undergoing CCRT and ≤45.80 in patients undergoing RT, the PFS and OS in patients with lower PNI were significantly shorter compared with those in patients with higher PNI (PFS and OS with CCRT, P<0.001 and P<0.001, respectively; PFS and OS with RT, P=0.002 and P=0.008, respectively). Multivariate analyses also identified low PNI as an independent prognostic factor for PFS and OS in patients receiving CCRT. Therefore, low PNI was shown to predict poor prognosis in patients with cervical cancer. PMID:27900086

  15. 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.

  16. Prognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide.

    PubMed

    Nagane, Motoo; Kobayashi, Keiichi; Ohnishi, Akiko; Shimizu, Saki; Shiokawa, Yoshiaki

    2007-12-01

    Temozolomide (TMZ) is active against newly diagnosed glioblastoma (GBM), and O(6)-methylguanine-DNA methyltransferase (MGMT) is implicated in resistance to TMZ and nitrosoureas. We evaluated the efficacy and safety of the standard 5-day TMZ regimen in patients with recurrent GBM after initial therapy including nitrosourea-based chemotherapy, in conjunction with an analysis of the prognostic value of MGMT protein expression regarding response to TMZ and survival. From September 2003 to January 2007, 30 patients having recurrent GBM received 150-200 mg/m(2)/day of TMZ for five consecutive days every 28 days. Tumor tissue from 19 patients was analysed for MGMT protein expression using western blotting, and 17 of them were assessable for a response. The overall response rate was 23.5% (one complete response and three partial responses). Six patients had stable disease (35.3%). Median progression-free survival (PFS) time was 2.2 months, and median overall survival (OS) time was 9.9 months from the initiation of TMZ therapy. Patients with low MGMT protein expression had a significantly improved PFS (P = 0.016) and OS (P = 0.019) compared to those with high expression. Both low MGMT expression (P = 0.040) and re-resection at relapse (P = 0.014) persisted as significant independent favorable prognostic factors for OS. The most common grade 3 and 4 hematological toxicity was lymphopenia (22.2%). The standard 5-day TMZ regimen resulted in moderate antitumor activity with an acceptable safety profile in patients with nitrosourea-pretreated recurrent GBM, and protein expression of MGMT is an important prognostic factor for patients treated with TMZ even after recurrence.

  17. 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

  18. The number of lymphoma-associated macrophages in tumor tissue is an independent prognostic factor in patients with follicular lymphoma.

    PubMed

    Andjelic, Bosko; Mihaljevic, Biljana; Todorovic, Milena; Bila, Jelena; Jakovic, Ljubomir; Jovanovic, Maja Perunicic

    2012-01-01

    The clinical course of patients with follicular lymphoma is variable from a slowly progressive disease to a progressive disease with a survival time of approximately 1 year. Many prognostic models have been suggested to identify high-risk patients. Recent gene profiling analysis showed that the clinical behavior of follicular lymphoma is determined by the properties of the nonmalignant tumor microenvironment. We investigated the role of lymphoma-associated macrophages (LAMs) in tumor tissue in patients with newly diagnosed follicular lymphoma. The LAM was determined immunohistochemically in lymph node tissue sections by anti-CD68 PG-M1 and analyzed through high-power field (HPF) magnification intrafollicularly (IF) and extrafollicularly. In our study, the patients who had an IF LAM count equal to or more than 10/HPF had significantly shorter overall survival (P=0.018) and 3 years of progression-free survival (P=0.034) compared with patients with <10 LAM/HPF. Multivariate analysis indicated that IF LAM/HPF ≥ 10 and Eastern Cooperative Oncology Group performance status >1 are independent prognostic factors for a poor outcome.

  19. The potential therapeutic applications and prognostic significance of metastasis-associated in colon cancer-1 (MACC1) in cancers

    PubMed Central

    2016-01-01

    The metastasis-associated in colon cancer-1 (MACC1) gene was identified in 2009. Expression of MACC1 was found to be significantly upregulated in primary and metastatic colon carcinomas compared to normal tissues or adenomas. The induction of MACC1 occurs at the crucial step of transition from a benign to a malignant phenotype. The aim of this review was to summarise current results of non-clinical and clinical studies on the role of MACC1 in the carcinogenesis and progression of cancer, as well its potential therapeutic and prognostic significance. The gene encoding the HGF receptor MET is a transcriptional target of MACC1. In addition to promoting the proliferation, invasion, and migration of colon cancer cells in cell culture and tumour growth and metastasis in mouse models, MACC1 also contributes to carcinogenesis and progression of colorectal cancer through the β-catenin signalling pathway and mesenchymal-epithelial transition. MACC1 knockdown with si/sh RNA was investigated in cell lines of different types of cancer. MACC1 is a promising therapeutic target for antitumour and antimetastatic intervention strategies for cancers. Here, it is presented as a potential independent prognostic indicator of reduced overall survival as well as of the occurrence of distant metastasis in patients with different types of cancer. PMID:27688722

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

    PubMed

    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.

  1. 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

  2. Prognostic Significance of Serum and Urinary Neopterin Concentrations in Patients with Rectal Carcinoma Treated with Chemoradiation.

    PubMed

    Zezulová, Michaela; Bartoušková, Marie; Hlídková, Eva; Juráňová, Jarmila; Červinková, Barbora; Kasalová, Eva; Adam, Tomáš; Krčmová, Lenka Kujovská; Solichová, Dagmar; Cwiertka, Karel; Vrána, David; Melichar, Bohuslav

    2016-01-01

    To analyze the prognostic significance of serum and urinary neopterin concentrations in patients with rectal adenocarcinoma treated with (chemo)radiation. Urinary and serum neopterin and peripheral blood cell count were determined in 49 patients with rectal carcinoma before the start of (chemo)radiation. Neopterin concentrations exhibited a significant inverse correlation with hemoglobin and positive correlation with leukocyte count, platelet count and platelet-to-lymphocyte ratio. Increased serum neopterin concentration was associated with significantly inferior relapse-free survival (RFS) and overall survival. However, a significant association was observed only in 28 patients treated in the neoadjuvant setting. Although increased urinary neopterin was also associated with inferior RFS and overall survival, this was not statistically significant. The neutrophil-to-lymphocyte ratio was also associated with poor prognosis. The data presented herein indicate a prognostic significance of serum neopterin concentrations in patients with rectal cancer treated with neoadjuvant chemoradiation. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Independent confirmation of a prognostic gene-expression signature in adult acute myeloid leukemia with a normal karyotype: a Cancer and Leukemia Group B study

    PubMed Central

    Radmacher, Michael D.; Marcucci, Guido; Ruppert, Amy S.; Mrózek, Krzysztof; Whitman, Susan P.; Vardiman, James W.; Paschka, Peter; Vukosavljevic, Tamara; Baldus, Claudia D.; Kolitz, Jonathan E.; Caligiuri, Michael A.; Larson, Richard A.; Bloomfield, Clara D.

    2006-01-01

    Patients with acute myeloid leukemia (AML) and normal karyotype are classified in an intermediate-risk group, albeit this subset is heterogeneous for clinical outcome. A recent complementary DNA microarray study identified a gene-expression signature that—when used to cluster normal karyotype patients—separated them into 2 prognostically relevant subgroups. We sought the first independent validation of the prognostic value of this signature. Using oligonucleotide microarrays to measure gene expression in samples from uniformly treated adults with karyotypically normal AML, we performed cluster analysis based on the previously identified signature. We also developed a well-defined classification rule using the signature to predict outcome for individual patients. Cluster analysis confirmed the prognostic utility of the signature: patient clusters differed in overall (P = .001) and disease-free (P = .001) survival. The signature-based classifier identified groups with differences in overall (P = .02) and disease-free (P = .05) survival. A strong association of the outcome classifier with the prognostically adverse FLT3 internal tandem duplication (FLT3 ITD) potentially explained the prognostic significance of the signature. However, in the subgroup of patients without FLT3 ITD there was a moderate difference in survival for the classifier-derived groups. Our analysis confirms the applicability of the gene-expression profiling strategy for outcome prediction in cytogenetically normal AML. PMID:16670265

  4. Determinants and Prognostic Significance of Symptomatic Status in Patients with Moderately Dysfunctional Bicuspid Aortic Valves

    PubMed Central

    Lee, Soo Youn; Shim, Chi Young; Hong, Geu-Ru; Cho, In Jeong; Chang, Hyuk-Jae; Ha, Jong-Won; Chung, Namsik

    2017-01-01

    Background We aimed to identify the clinical and echocardiographic determinants of symptoms and their prognostic implications in patients with moderately dysfunctional bicuspid aortic valves (BAVs). Methods Among 1,019 subjects in the BAV registry treated in a single tertiary care center, the records of 127 patients (85 men, age 58±13 years) with moderately dysfunctional BAVs were comprehensively reviewed. The patients were divided into two groups based on symptom status: asymptomatic (n = 80) vs. symptomatic (n = 47). The primary end-point was defined as a composite of aortic valve surgery, hospitalization for heart failure, and any cause of death. Results The symptomatic group had a higher proportion of females, hypertension, aortic stenosis, and aortopathy than did the asymptomatic group. The symptomatic group showed lower e′ (5.5±1.7 vs. 6.5±2.2 cm/s, p = 0.003), higher E/e′ (13.3 ± 4.9 vs. 10.9±3.7, p = 0.002), and larger left atrial volume index (29.9±11.4 vs. 24.6±9.1 ml/m2, p = 0.006) than did the asymptomatic group. In multivariate logistic regression analysis, female gender (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.10–7.36, p = 0.031), hypertension (OR 3.07, 95% CI 1.20–7.82, p = 0.019), moderate aortic stenosis (OR 5.33 5.78, 95% CI 1.99–16.83, p = 0.001), E/e′ >15 (OR 3.82, 95% CI 1.03–11.19, p = 0.015), and aortopathy (OR 2.76, 95% CI 1.07–7.10, p = 0.035) were independently correlated with symptom status. The symptomatic group showed a significantly lower rate of event-free survival during the 8-year follow-up period (54±9% vs. 68±10%, p = 0.001). Conclusions In patients with moderately dysfunctional BAVs, the presence of moderate aortic stenosis, aortopathy, and diastolic dysfunction determines symptom status, along with female gender and hypertension. Symptom status was associated with clinical outcomes. PMID:28060855

  5. Subclassification of stage IV gastric cancer (IVa, IVb, and IVc) and prognostic significance of substages.

    PubMed

    Ma, Yan; Xue, Yingwei; Li, Yanfeng; Lan, Xiuwen; Zhang, Yongle; Zhang, Ming

    2010-03-01

    Although the prognosis of stage IV gastric cancer is poor, some patients with stage IV gastric cancer had a long-term survival after gastrectomy. The objective of this study was to subclassify stage IV gastric cancer according to survival differences, evaluate the prognosis by substage, and identify the factors associated with patient survival in each substage. The data from 1,176 patients who underwent gastric resection for stage IV gastric cancer between 1988 and 2007 at Tumor Hospital of Harbin Medical University were reviewed retrospectively. The patients were divided into three substages according to the survival differences: stage IVa (T1-2N3M0), stage IVb (T3N3M0 and T4N1-2M0), and stage IVc (T4N3M0 and TanyNanyM1). The clinicopathological characteristics as well as survival of the patients were evaluated retrospectively by substage. There were no significant differences in survival among T3N3M0, T4N1M0, and T4N2M0 groups (p = 0.884) and between T4N3M0 and TanyNanyM1 groups (p = 0.192). The 5-year survival rates in stage IVa (T1-2N3M0), stage IVb (T3N3M0 and T4N1-2M0), and stage IVc (T4N3M0 and TanyNanyM1) were 22.7%, 9.9%, and 2.2%, respectively (p < 0.001). Multivariate analysis showed the following independent prognostic factors for survival: subclassification, operation type, number of retrieved lymph nodes, curability, and chemotherapy for stage IV gastric cancer; curability, chemotherapy, and number of retrieved lymph nodes for stage IVa and IVb; chemotherapy and operation type for stage IVc. For 406 patients with curative resection in stage IVa and IVb, hematogenous recurrence (35.9%) was the dominant recurrence pattern in stage IVa, whereas the most common patterns of recurrence were peritoneal (40.8%) and locoregional recurrence (31.8%) in stage IVb. Subclassification of stage IV gastric cancer into IVa (T1-2N3M0), IVb (T3N3M0 and T4N1-2M0), and IVc (T4N3M0, TanyNanyM1) may be helpful to predict the outcome and determine the therapeutic strategies

  6. Prognostic significance of preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of patients with gastric cardia cancer

    PubMed Central

    Qiao, Yu-Feng; Chen, Chuan-Gui; Yue, Jie; Ma, Ming-Quan; Ma, Zhao; Yu, Zhen-Tao

    2017-01-01

    AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19 (CK19) and carcinoembryonic antigen (CEA) mRNA levels in peripheral blood of patients with gastric cardia cancer (GCC). METHODS We detected the preoperative and postoperative mRNA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors. RESULTS Elevated preoperative and postoperative CK19 and CEA mRNA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 mRNA, and preoperative and postoperative CEA mRNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status (P = 0.018), preoperative CK19 (P = 0.035) and CEA (P = 0.011) mRNA levels were independent prognostic factors for overall survival (OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively (P < 0.001). CONCLUSION Elevated preoperative CK19 and CEA mRNA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk. PMID:28293089

  7. Incorporating biologic measurements (SF(2), CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy.

    PubMed

    Buffa, F M; Davidson, S E; Hunter, R D; Nahum, A E; West, C M

    2001-08-01

    To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF(2)) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. Measurements of SF(2) and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp(alpha,rho)). Regression analysis was performed to assess the prognostic power of tcp(alpha,rho) vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF(2) and CFE measurements alone. In a univariate regression analysis of 44 patients, tcp(alpha,rho) was a better prognostic factor for both local control and survival (p < 0.001 and p = 0.049, respectively) than SF(2) alone (p = 0.009 for local control, p = 0.29 for survival) or CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp(alpha,rho) emerged as the most important prognostic factor for local control (p < 0.001, relative risk of 2.81). After allowing for tcp(alpha,rho), CFE was still a significant independent prognostic factor for local control, whereas SF(2) was not. The sensitivities of tcp(alpha,rho) and SF(2) as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. A Poisson tcp model incorporating individual SF(2), CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.

  8. Prognostic significance of AMPK in human malignancies: A meta-analysis

    PubMed Central

    Cheng, Ji; Shuai, Xiaoming; Gao, Jinbo; Cai, Ming; Wang, Guobin; Tao, Kaixiong

    2016-01-01

    Background AMPK is a well-investigated kinase mediating cellular metabolism and stress responses. However, its indicative role in survival prognosis remains ill-defined. Therefore we performed this meta-analysis in order to clarify the prognostic impact of AMPK expression in human malignancies. Methods Literatures were retrieved via searching databases of PubMed, Web of Science, Embase and Cochrane Library. Studies comparing the prognostic significance between different AMPK levels among human malignancies were included into the pooled analysis. The statistical procedures were conducted by Review Manager 5.3 and the effect size was displayed by model of odds ratio. Subgroup analyses were additionally implemented to disclose the potential confounding elements. The outcome stability was examined by sensitivity analysis, and both Begg's test and Egger's test were utilized to detect the publication bias across the included studies. Results 21 retrospective cohorts were eventually obtained with a total sample-size of 9987 participants. Patients with higher AMPK expression had better outcomes of 3-year overall survival (P<0.0001), 5-year overall survival (P<0.0001), 10-year overall survival (P<0.0001), 3-year disease free survival (P<0.0001), 5-year disease free survival (P=0.002) and 10-year disease free survival (P=0.0004). Moreover, the majority of subgroup results also verified the favorably prognostic significance of AMPK over-expression. The outcome stability was confirmed by sensitivity analysis. Results of Begg's (P=0.76) and Egger's test (P=0.09) suggested that there was no publication bias within the included trials. Conclusions Higher expression of AMPK significantly indicates better prognosis in human malignancies. PMID:27716618

  9. Prognostic significance of E-cadherin and N-cadherin expression in Gliomas.

    PubMed

    Noh, Myung-Giun; Oh, Se-Jeong; Ahn, Eun-Jung; Kim, Yeong-Jin; Jung, Tae-Young; Jung, Shin; Kim, Kyung-Keun; Lee, Jae-Hyuk; Lee, Kyung-Hwa; Moon, Kyung-Sub

    2017-08-29

    Epithelial-mesenchymal transition (EMT), principally involving an E-cadherin to N-cadherin shift, linked to tumor invasion or metastasis, and therapeutic resistance in various human cancer. A growing body of recent evidence has supported the hypothesis that EMT play a crucial role in the invasive phenotype of gliomas. To evaluate the prognostic connotation of EMT traits in glioma, expression of E-cadherin and N-cadherin was explored in a large series of glioma patients in relation to patient survival rate. Expressions of E- and N-cadherin were examined using immunohistochemical analysis in 92 glioma cases diagnosed at our hospital. These markers expressions were also explored in 21 cases of fresh frozen glioma samples and in glioma cell lines by Western blot analysis. Expression of E-cadherin was observed in eight cases (8.7%) with weak staining intensity in the majority of the immunoreactive cases (7/8). Expression of N-cadherin was identified in 81 cases (88.0%) with high expression in 64 cases (69.5%). Fresh frozen tissue samples and glioma cell lines showed similar results by Western blot analysis. There was no significant difference in either overall survival (OS) or progression-free survival (PFS) according to E-cadherin expression (P > 0.05). Although the OS rates were not affected by N-cadherin expression levels (P = 0.138), PFS increased in the low N-cadherin expression group with marginal significance (P = 0.058). The survival gains based on N-cadherin expression levels were significantly augmented in a larger series of publicly available REMBRANDT data (P < 0.001). E- and N-cadherin, as representative EMT markers, have limited prognostic value in glioma. Nonetheless, the EMT process in gliomas may be compounded by enhanced N-cadherin expression supported by unfavorable prognostic outcomes.

  10. DC-SCRIPT: nuclear receptor modulation and prognostic significance in primary breast cancer.

    PubMed

    Ansems, M; Hontelez, S; Looman, M W G; Karthaus, N; Bult, P; Bonenkamp, J J; Jansen, J H; Sweep, F C G J; Span, P N; Adema, Gosse J

    2010-01-06

    Nuclear receptors, including estrogen receptor (ER), progesterone receptor (PR)-B, peroxisome proliferator-activated receptor gamma, and retinoic acid receptor alpha, have been implicated in breast cancer etiology and progression. We investigated the role of dendritic cell-specific transcript (DC-SCRIPT) as coregulator of these nuclear receptors and as a prognostic factor in breast cancer. The effect of DC-SCRIPT on the transcriptional activity of nuclear receptors was assessed by luciferase reporter assays. DC-SCRIPT expression in normal and tumor tissue from breast cancer patients was analyzed by polymerase chain reaction and immunohistochemistry. The prognostic value of tumor DC-SCRIPT mRNA expression was assessed in three independent cohorts of breast cancer patients: a discovery group (n = 47) and a validation group (n = 97) (neither of which had received systemic adjuvant therapy) and in a tamoxifen-treated validation group (n = 68) by using a DC-SCRIPT to porphobilinogen deaminase transcript ratio cutoff of 0.15 determined in the discovery group. Univariate and multivariable Cox proportional hazards model analyses were performed. All statistical tests were two-sided. DC-SCRIPT suppressed ER- and PR-mediated transcription in a ligand-dependent fashion, whereas it enhanced the retinoic acid receptor alpha- and peroxisome proliferator-activated receptor gamma-mediated transcription. In breast tissue samples from nine patients, DC-SCRIPT mRNA was expressed at lower levels in the tumor than in the corresponding normal tissue (P = .010). Patients in the discovery group with high tumor DC-SCRIPT mRNA levels (66%) had a longer disease-free interval than those with a low DC-SCRIPT mRNA level (34%) (hazard ratio [HR] of recurrence for high vs low DC-SCRIPT level = 0.23, 95% confidence interval [CI] = 0.06 to 0.93, P = .039), which was confirmed in the validation group (HR of recurrence = 0.50, 95% CI = 0.26 to 0.95, P = .034). This prognostic value was confined to

  11. Prognostic significance of ATM and cyclin B1 in pancreatic neuroendocrine tumor.

    PubMed

    Shin, Jae Uk; Lee, Chang Hoon; Lee, Kyu Taek; Lee, Jong Kyun; Lee, Kwang Hyuck; Kim, Kwang Min; Kim, Kyoung-Mee; Park, Sang-Mo; Rhee, Jong Chul

    2012-10-01

    Ataxia telangiectasia mutated kinase (ATM) and cyclin B1 are involved in cell cycle control. The prognostic significance of both molecules has not yet been investigated in pancreatic neuroendocrine tumors. The aim of this study was to evaluate the clinical and prognostic significance of ATM and cyclin B1 in patients with pancreatic neuroendocrine tumors. A total of 107 pancreatic neuroendocrine tumor specimens that were surgically resected were immunohistochemically investigated using the tissue microarray technique. Clinicopathologic results and survival were evaluated retrospectively. High expression of ATM and cyclin B1 was related to well-differentiated endocrine tumors of the World Health Organization (WHO) classification, but not related to TNM stages. The high ATM expression group (ATM ≥ 4) had a significantly smaller tumor size, lower recurrence rate, more number of functioning tumor, and well differentiation of WHO classification. The high cyclin B1 expression group (cyclin B1 ≥ 5) was related to smaller tumor size, less vascular invasion, less recurrence rate, and less death rate. However, cyclin B1 was the only significant factor for survival following multivariate analysis (p = 0.008; OR, 0.54; 95 % CI, 0.35-0.85). The current results suggested that expression of ATM and cyclin B1 may be useful markers to identify patients with poor prognosis who may benefit from close follow-up and aggressive therapy in pancreatic neuroendocrine tumors.

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

    PubMed Central

    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

  13. 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

    2015-06-23

    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.

  14. 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

  15. Frailty is an independent prognostic marker in elderly patients with myocardial infarction.

    PubMed

    Alonso Salinas, Gonzalo Luis; Sanmartin, Marcelo; Pascual Izco, Marina; Rincon, Luis Miguel; Pastor Pueyo, Pablo; Marco Del Castillo, Alvaro; Garcia Guerrero, Alberto; Caravaca Perez, Pedro; Recio-Mayoral, Alejandro; Camino, Asuncion; Jimenez-Mena, Manuel; Zamorano, José Luis

    2017-07-16

    Acute coronary syndrome (ACS) patients are increasingly older. Conventional prognostic scales include chronological age but do not consider vulnerability. In elderly patients, a frail phenotype represents a better reflection of biological age. This study aims to determine the prevalence of frailty and its influence on patients age ≥75 years with ACS. Patients age ≥75 years admitted due to type 1 myocardial infarction were included in 2 tertiary hospitals, and clinical data were collected prospectively. Frailty was defined at admission using the previously validated Survey of Health Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the combination of death or nonfatal myocardial reinfarction during a follow-up of 6 months. Major bleeding (hemoglobin decrease ≥3 g/dL or transfusion needed) and readmission rates were also explored. A total of 234 consecutive patients were included. Frail patients (40.2%) had a higher-risk profile, based on higher age and comorbidities. On multivariate analysis, frailty was an independent predictor of the combination of death or nonfatal myocardial reinfarction (adjusted hazard ratio [aHR]: 2.54, 95% confidence interval [CI]: 1.12-5.79), an independent predictor of the combination of death, nonfatal myocardial reinfarction, or major bleeding (aHR: 2.14, 95% CI: 1.13-4.04), and an independent predictor of readmission (aHR: 1.80, 95% CI: 1.00-3.22). Frailty phenotype at admission is common among elderly patients with ACS and is an independent predictor for severe adverse events. It should be considered in future risk-stratification models. © 2017 Wiley Periodicals, Inc.

  16. 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

  17. Cell polarity protein CRB3 is an independent favorable prognostic factor for clear cell renal cell carcinoma.

    PubMed

    Mao, Xiaona; Li, Pingping; Ren, Yu; Li, Juan; Zhou, Can; Yang, Jin; Liu, Peijun

    2015-02-01

    Epithelial cells possess apical‑basal polarity and loss of epithelial cell polarity contributes to tumorigenesis and cancer progression. The Crumbs (CRB) polarity protein plays a crucial role in epithelial polarity maintenance, apical membrane formation, and tissue morphogenesis. Although evidence is increasing on involvement of deregulated polarity proteins in cancers, little is currently known about the roles of the CRB (Drosophila), especially the roles of CRB3, a homolog of the CRB, in clear cell renal cell carcinoma (ccRCC). Studies have shown that CRB3 may act as a tumor suppressor in non‑human mammalian cells; the study here was aimed to examine the expression status of CRB3 in ccRCC and the relationships between CRB3 expression and clinicopathologic parameters of ccRCC patients. Our results showed that CRB3 was weakly expressed in ccRCC tissues, but strongly expressed in adjacent normal kidney tissues. Patients with loss of CRB3 expression showed a significantly shorter overall survival (OS) than patients with positive CRB3 expression. Our results suggested that CRB3 may be an independent favorable prognostic factor for patients with ccRCC. We also found that overexpression of CRB3 restrained invasion and migration of 786‑O cells and loss of CRB3 expression promoted invasion and migration of human embryonic kidney 293T (HEK 293T) cells. This finding may explain why the negative CRB3 expression was associated with poor prognosis in human ccRCC. Altogether, our data demonstrated that CRB3 may be used as a new independent favorable prognostic factor for human ccRCC.

  18. Type 2 diabetes is an independent negative prognostic factor in patients undergoing surgical resection of a WHO grade I meningioma.

    PubMed

    Nayeri, Arash; Chotai, Silky; Prablek, Marc A; Brinson, Philip R; Douleh, Diana G; Weaver, Kyle D; Thompson, Reid C; Chambless, Lola

    2016-10-01

    In recent years, there has been increased recognition of the relationship between type 2 diabetes mellitus (DM) and poor outcomes following a variety of surgical procedures. We sought to study the role of type 2 DM as a prognostic factor affecting the long-term survival of patients undergoing surgical resection of a WHO Grade I meningioma. We conducted a retrospective cohort study on 196 patients who had a WHO Grade I meningioma resected at our institution between 2001 and 2013. The medical record was reviewed to identify a pre-existing diagnosis of type 2 DM. Patient mortality was reviewed by medical record and Social Security Death Index (SSDI). Variables associated with survival in a univariate analysis were included in the multivariate Cox model if P<0.10. Variables with probability values >0.05 were then removed from the multivariate model in a step-wise fashion. 33 (17%) patients had pre-existing diagnoses of type 2 DM prior to clinical presentation. Mean survival time in diabetic patients was 52.1 months compared to 160.9 months in non-diabetics. The decreased survival rate and time in patients with type 2 DM were found to be statistically significant (p=0.008 and p<0.0001, respectively). In a multivariate Cox analysis, a pre-existing history of type 2 DM was independently associated with decreased survival following the resection of a WHO Grade I meningioma (HR=2.6, p=0.045). A pre-existing diagnosis of type 2 DM is an independent negative prognostic indicator following the resection of a WHO Grade I meningioma. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. DNA content in high and intermediate grade non-Hodgkin's lymphoma-prognostic significance and clinicopathological correlations.

    PubMed Central

    Cowan, R. A.; Harris, M.; Jones, M.; Crowther, D.

    1989-01-01

    Flow cytometric (FCM) estimation of DNA content has been performed on tumour tissue from 197 patients with high and intermediate grade non-Hodgkin's lymphoma (NHL) to investigate the clinicopathological correlations and prognostic significance of DNA ploidy and proliferative activity. Fifty-one per cent of tumours were diploid; the remaining non-diploid tumours were near diploid (14%), aneuploid (28%) and tetraploid (7%). In 81 tumours multiple analyses were performed from different regions of the tumour, ploidy discrepancy was seen within the same tumour in 13/81 tumours (16%), and intra-tumour variation in proliferative index (PI) in 72 tumours was estimated at +/- 5%. Ploidy status did not correlate with histological subtype (Kiel or Rappaport), Ann Arbor stage or the site of disease at presentation. There was no significant difference in response rate, relapse-free survival (RFS) or overall survival rate between the different ploidy categories. Tumour proliferative index (PI) varied markedly between patients (range 2-51%, median 14%). A significant association was observed between PI and histological subtype in the Kiel classification (P = 0.001). The median PI for the lymphoblastic lymphomas was 20% compared with 10% for the centrocytic tumours. An elevated PI was significantly associated with a reduced rate (P = 0.023), with 71% of patients with a low PI (less than 20%) achieving complete remission (CR) compared with 49% patients with a high PI (greater than 20%). Despite this correlation with CR, PI was not significantly associated with overall survival. When the DNA data was combined with over 20 other potential prognostic factors in multivariate analysis, ploidy and proliferative activity did not prove to be of independent prognostic significance for response, RFS or overall survival. In 20 patients additional biopsy material was available from the site of subsequent relapse. In these cases, although the histology at relapse remained unchanged, ploidy

  20. Prognostic significance of soluble mesothelin in malignant pleural mesothelioma: a meta-analysis

    PubMed Central

    Shen, Cheng; Lai, Yutian; Wang, Mingming; Che, Guowei

    2017-01-01

    Background Soluble mesothelin is beneficial to detect the progression and the treatment response of malignant pleural mesothelioma. However, the prognostic value of soluble mesothelin in malignant pleural mesothelioma remains unclear. Methods Hazard ratio with 95% CI was used to evaluate the prognostic value of soluble mesothelin and the effect of clinicopathological characteristics on the survival of malignant pleural mesothelioma. Results Eight eligible studies involving 579 patients were selected for this meta-analysis. The results showed that soluble mesothelin level was significantly correlated with the survival of malignant pleural mesothelioma (pooled HR: 1.958, 95%CI: 1.531-2.504, p = 0.000; heterogeneity test: I2 = 1.1%, p = 0.421). In addition, the survival of malignant pleural mesothelioma was significantly correlated with some clinicopathological characteristics such as tumor histology (HR = 3.214, 95% CI = 2.071-4.988, p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.623) and tumor stage (HR = 2.007; 95% CI = 1.477-2.727; p = 0.000; heterogeneity test: I2 = 0.0%, p = 0.966). Conclusions The survival of malignant pleural mesothelioma is significantly correlated with tumor histology and tumor stage. Furthermore, high soluble mesothelin level may lead to a poor prognosis for malignant pleural mesothelioma patients. PMID:28507279

  1. The prognostic significance of beta human chorionic gonadotrophin and its metabolites in women with cervical carcinoma.

    PubMed Central

    Crawford, R A; Iles, R K; Carter, P G; Caldwell, C J; Shepherd, J H; Chard, T

    1998-01-01

    AIMS: To examine long term survival of women with primary and recurrent cervical carcinoma in relation to (1) excretion of beta-core (a urinary metabolite of beta human chorionic gonadotrophin (beta hCG)) and (2) beta hCG immunostaining of the tumours, to determine the suitability of these markers for assessing prognosis. METHODS: This was a prospective observational study undertaken in a gynaecological oncology centre: 57 women with primary cervical cancer and 42 with recurrent disease were recruited between January 1990 and September 1992. Kaplan-Meier survival analysis with the log rank test was used to assess survival differences with survival rate given per year of follow up. RESULTS: In primary disease, the four year survival for the beta-core negative group was 79%, compared with 14% for the beta-core positive group (p = 0.001). This was still significant for early stage disease or squamous lesions alone. In recurrent disease, beta-core positivity was not prognostically significant. Immunohistochemistry was of no prognostic significance in either group. CONCLUSIONS: beta-core excretion appears to be useful in assessing prognosis of primary cervical cancer but not of recurrent disease. A large prospective study of urinary beta-core in early stage cervical cancer is needed to determine whether it can be used as an index for modifying treatment. PMID:9930074

  2. Prognostic significance of neutrophil-lymphocyteratio/platelet-lymphocyteratioin lung cancers: a meta-analysis

    PubMed Central

    Yang, Hong-Bo; Xing, Meng; Ma, Lei-Na; Feng, Ling-Xin; Yu, Zhuang

    2016-01-01

    Setting For now, hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. Many articles have confirm that neutrophil to lymphocyte ratio(NLR) and platelet–lymphocyte ratio (PLR) are relate with poor prognosis in various types of tumors. Objective To investigate the association between NLR/PLR and progression free survival (PFS), overall survival (OS) and clinicopathologic parameters in lung cancer patients. Design We performed relevant searches in PubMed database, Google Scholar, Springer Link. We included retrospective cohort studies that reported hazard ratios with 95% confidence intervals for the NLR or PLR and PFS or OS. Results Both high NLR (P < 0.00001) and high PLR (P = 0.01) were significantly predictive of poorer OS. It also demonstrated that elevated NLR predicted poorer PFS (P = 0.0002). High NLR was significantly associated with deeper Invasive of tumor, (P = 0.006) extensive lymph nodetastasis(N2–3) (P = 0.01), poor differentiation (P = 0.0002) and vascular invasion(P = 0.002). There was no evidence of publication bias. Subgroup analysis indicated that little evidence of heterogeneity. However, PLR has no prognostic significance for SCLC. Conclusions We provides further evidence in support of elevated NLR and PLR were predictors of poor OS and PFS in patients with lung cancer. Given this, NLR and PLR may be markers to report treatment outcomes. PMID:27732958

  3. Clinicopathological and prognostic significance of COX-2 immunohistochemical expression in breast cancer: a meta-analysis

    PubMed Central

    Xu, Feng; Li, Mengxin; Zhang, Chao; Cui, Jianxiu; Liu, Jun; Li, Jie; Jiang, Hongchuan

    2017-01-01

    The prognostic significance of COX-2 in patients with breast cancer remains controversial. The aims of our meta-analysis are to evaluate its association with clinicopathological characteristics and prognostic value in patients with breast cancer. PubMed, EMBASE, Web of Science, the Ovid Database and Grey literature were systematically searched up to May 2016. Twenty-one studies including 6739 patients with breast cancer were analyzed. The meta-analysis indicated that the incidence difference of COX-2 expression was significant when comparing the lymph node positive group to negative group (OR = 1.76, 95% CI [1.30, 2.39]) and the tumor size ≥ 2cm group to the tumor size < 2cm group (OR = 1.71, 95% CI [1.22, 2.39]). None of other clinicopathological parameters such as the ER status, PR status, HER2 status and the vascular invasion status were associated with COX-2 overexpression. The detection of COX-2 was significantly correlated with the disease-free survival (DFS) of patients (HR = 1.58, 95% CI [1.23, 2.03]) and the overall survival (OS) of patients (HR = 1.51, 95% CI [1.31, 1.72]). Our meta-analysis demonstrates that the presence of high levels of COX-2 is associated with poor prognosis for breast cancer patients and predicts bigger tumor size and lymph node metastasis. PMID:27999206

  4. The prognostic value of lymph node ratio in colon cancer is independent of resection length.

    PubMed

    Amri, Ramzi; Klos, Coen L; Bordeianou, Liliana; Berger, David L

    2016-08-01

    Lymph node ratio (LNR), the ratio of tumor-positive lymph nodes (+LN) to the total number of resected lymph nodes (rLN), predicts recurrence and survival in colon cancer. Variations in colonic resection length (RL) may influence rLN, +LN, or both, thereby potentially impacting LNR and its prognostic value in colon cancer. All colon cancer patients treated surgically at our center from 2004 to 2011 were included in an institutional review board-approved data repository (n = 1,039). Larger RL was associated with increased rLN (ρ = .22; P < .001) but not with +LN (P = .21). In node-positive patients (n = 411), RL-adjusted LNR had weaker correlations with death (ρ = .338 vs .373, both P < .001) or metastatic disease (ρ = .303 vs .345; both P < .001) and a smaller area under the curve (death: .695 vs .715, metastasis: .675 vs .699). Findings were similar in segmental, extended segmental, and total colectomy subgroups. Provided that resections are performed following standard oncologic principles, our analysis shows that RL does not significantly impact the prognostic value of LNR in colon cancer. Correcting LNR for RL seems redundant and may even act as noise distorting LNR values. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. 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

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

    PubMed Central

    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

    2016-01-01

    Abstract 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

  7. 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

  8. ANLN is a prognostic biomarker independent of Ki-67 and essential for cell cycle progression in primary breast cancer.

    PubMed

    Magnusson, Kristina; Gremel, Gabriela; Rydén, Lisa; Pontén, Victor; Uhlén, Mathias; Dimberg, Anna; Jirström, Karin; Pontén, Fredrik

    2016-11-18

    Anillin (ANLN), an actin-binding protein required for cytokinesis, has recently been presented as part of a prognostic marker panel in breast cancer. The objective of the current study was to further explore the prognostic and functional value of ANLN as a single biomarker in breast cancer. Immunohistochemical assessment of ANLN protein expression was performed in two well characterized breast cancer cohorts (n = 484) with long-term clinical follow-up data and the results were further validated at the mRNA level in a publicly available transcriptomics dataset. The functional relevance of ANLN was investigated in two breast cancer cell lines using RNA interference. High nuclear fraction of ANLN in breast tumor cells was significantly associated with large tumor size, high histological grade, high proliferation rate, hormone receptor negative tumors and poor prognosis in both examined cohorts. Multivariable analysis showed that the association between ANLN and survival was significantly independent of age in cohort I and significantly independent of proliferation, as assessed by Ki-67 expression in tumor cells, age, tumor size, ER and PR status, HER2 status and nodal status in cohort II. Analysis of ANLN mRNA expression confirmed that high expression of ANLN was significantly correlated to poor overall survival in breast cancer patients. Consistent with the role of ANLN during cytokinesis, transient knock-down of ANLN protein expression in breast cancer cell lines resulted in an increase of senescent cells and an accumulation of cells in the G2/M phase of the cell cycle with altered cell morphology including large, poly-nucleated cells. Moreover, ANLN siRNA knockdown also resulted in decreased expression of cyclins D1, A2 and B1. ANLN expression in breast cancer cells plays an important role during cell division and a high fraction of nuclear ANLN expression in tumor cells is correlated to poor prognosis in breast cancer patients, independent of Ki-67, tumor size

  9. Prognostic significance and the role in TNM stage of extranodal metastasis within regional lymph nodes station in gastric carcinoma

    PubMed Central

    Chen, Xiao-Long; Zhao, Lin-Yong; Xue, Lian; Xu, Yu-Hui; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Yang, Kun; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    The role of extranodal metastasis (ENM) in TNM stage in gastric carcinoma (GC) is controversial. This study was aimed to make a detailed investigation of the prognostic significance and the role in TNM stage of ENM in GC. The patients with primary GC, who underwent gastrectomy with curative intention in West China Hospital from January 2005 to December 2011, were retrospectively enrolled. The prognosis and clinicopathological traits were compared between ENM positive (ENMP) and negative (ENMN) groups in all patients, TNM I-II, III and IV stages, respectively. The significance of the number and the role in TNM stage of ENM were also assessed. In our study, 1457 patients were enrolled, with 1324 (90.9%) in ENMN group and 133 (9.1%) in ENMP group. ENMP group had significantly more advanced GC and worse prognosis (all p<0.05) than ENMN group in all patients, TNM I-II stages and TNM III stage. ENM>2 subgroup had remarkably larger tumor size (p=0.002) and more advanced N stage (p=0.016) than ENM=1-2 subgroup. The number of ENM was an independent prognostic factor in ENMP group (p=0.029). The prognosis of ENM>2 in TNM I-III stages was significantly worse than ENMN patients in TNM III stage. The C-index of TNM stage plus the number of ENM was significantly higher than that of current TNM stage alone (p=0.005). In conclusion, the patients in ENMP subgroup had more advanced GC and worse prognosis than those in ENMN subgroup. It might be more reasonable to categorize ENM>2 into TNM IV stage. PMID:27563811

  10. Prognostic significance and the role in TNM stage of extranodal metastasis within regional lymph nodes station in gastric carcinoma.

    PubMed

    Chen, Xiao-Long; Zhao, Lin-Yong; Xue, Lian; Xu, Yu-Hui; Zhang, Wei-Han; Liu, Kai; Chen, Xin-Zu; Yang, Kun; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-10-11

    The role of extranodal metastasis (ENM) in TNM stage in gastric carcinoma (GC) is controversial. This study was aimed to make a detailed investigation of the prognostic significance and the role in TNM stage of ENM in GC. The patients with primary GC, who underwent gastrectomy with curative intention in West China Hospital from January 2005 to December 2011, were retrospectively enrolled. The prognosis and clinicopathological traits were compared between ENM positive (ENMP) and negative (ENMN) groups in all patients, TNM I-II, III and IV stages, respectively. The significance of the number and the role in TNM stage of ENM were also assessed. In our study, 1457 patients were enrolled, with 1324 (90.9%) in ENMN group and 133 (9.1%) in ENMP group. ENMP group had significantly more advanced GC and worse prognosis (all p<0.05) than ENMN group in all patients, TNM I-II stages and TNM III stage. ENM>2 subgroup had remarkably larger tumor size (p=0.002) and more advanced N stage (p=0.016) than ENM=1-2 subgroup. The number of ENM was an independent prognostic factor in ENMP group (p=0.029). The prognosis of ENM>2 in TNM I-III stages was significantly worse than ENMN patients in TNM III stage. The C-index of TNM stage plus the number of ENM was significantly higher than that of current TNM stage alone (p=0.005). In conclusion, the patients in ENMP subgroup had more advanced GC and worse prognosis than those in ENMN subgroup. It might be more reasonable to categorize ENM>2 into TNM IV stage.

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

    PubMed

    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

    2016-05-01

    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.

  12. Lack of Ephrin Receptor A1 Is a Favorable Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

    PubMed Central

    Diezel, Michael; Meinhardt, Matthias; Zastrow, Stefan; Fuessel, Susanne; Wirth, Manfred P.; Baretton, Gustavo B.

    2014-01-01

    The EPH receptor tyrosine kinases and their cell-bound ligands, the ephrins, have been shown to be associated with cancer development and progression. In this study, mRNA and protein expression of the receptors EPHA1 and EPHA2 as well as of their ligand EFNA1 and their prognostic relevance in clear cell renal cell carcinoma was evaluated. Gene expression was measured in 75 cryo-preserved primary tumors and matched non-malignant renal specimens by quantitative PCR. Protein expression was analyzed by immunohistochemistry on tissue microarrays comprising non-malignant, primary tumors and metastatic renal tissues of 241 patients. Gene and protein expression of all three factors was altered in tumor specimens with EPHA1 and EPHA2 being generally diminished in tumors compared to normal renal tissue, whereas EFNA1 was commonly elevated. A positive EPHA1 and EPHA2 protein staining as well as a low EFNA1 protein level were significantly linked to more aggressive tumor features, but only a positive EPHA1 immunoreactivity was significantly associated with poor survival. In subgroup analyses, EPHA1 and EPHA2 protein levels were significantly higher in metastatic than in primary lesions. Patients with EPHA1/EPHA2-positive tumors or with tumors with positive EPHA1 and low EFNA1 immunoreactivity had the shortest survival rates compared to the respective other combinations. In a multivariate model, EPHA1 was an independent prognostic marker for different survival endpoints. In conclusion, an impaired EPH-ephrin signaling could contribute to the pathogenesis and progression of clear cell renal cell carcinoma. PMID:25025847

  13. Characterization of Desmoglein Expression in the Normal Prostatic Gland. Desmoglein 2 Is an Independent Prognostic Factor for Aggressive Prostate Cancer

    PubMed Central

    Barber, Alison G.; Castillo-Martin, Mireia; Bonal, Dennis M.; Rybicki, Benjamin A.; Christiano, Angela M.; Cordon-Cardo, Carlos

    2014-01-01

    Purpose The expression of desmogleins (DSGs), which are known to be crucial for establishing and maintaining the cell-cell adhesion required for tissue integrity, has been well characterized in the epidermis and hair follicle; however, their expression in other epithelial tissues such as prostate is poorly understood. Although downregulation of classical cadherins, such as E-cadherin, has been described in prostate cancer tissue samples, the expression of desmogleins has only been previously reported in prostate cancer cell lines. In this study we characterized desmoglein expression in normal prostate tissues, and further investigated whether Desmoglein 2 (DSG2) expression specifically can serve as a potential clinical prognostic factor for patients diagnosed with primary prostate cancer. Experimental Design We utilized immunofluorescence to examine DSG2 expression in normal prostate (n = 50) and in a clinically well-characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2 expression with clinico-pathological characteristics and biochemical recurrence was analyzed to assess its clinical significance. Results These studies revealed that DSG2 and DSG4 were specifically expressed in prostatic luminal cells, whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not expressed in normal prostate epithelium. Further analyses of DSG2 expression in prostate cancer revealed that reduced levels of this biomarker were a significant independent marker of poor clinical outcome. Conclusion Here we report for the first time that a low DSG2 expression phenotype is a useful prognostic biomarker of tumor aggressiveness and may serve as an aid in identifying patients with clinically significant prostate cancer. PMID:24896103

  14. Prognostic Significance of Left Ventricular Fibrosis in Patients With Congenital Bicuspid Aortic Valve.

    PubMed

    Lluri, Gentian; Renella, Pierangelo; Finn, J Paul; Vorobiof, Gabriel; Aboulhosn, Jamil; Deb, Arjun

    2017-10-01

    This study sought to evaluate the prognostic value of left ventricular (LV) fibrosis assessed by late gadolinium enhancement (LGE) of the myocardium during cardiac magnetic resonance (CMR) imaging in patients with bicuspid aortic valve (BAV), which is associated with early aortic valve fibrosis and calcification. To what degree the LV myocardial wall is affected by fibrosis and its prognostic value is currently unknown. This is a retrospective, single-center study evaluating all adult patients with BAV who had CMR and followed from March 2002 to March 2016. CMR and transthoracic echocardiogram images were reviewed. Clinical data were abstracted from the electronic medical record. A total of 29 patients were included in the study, of which 11 (38%) had CMR studies that demonstrated the presence of LGE. Patients with LGE had significantly higher aortic valve mean gradients by echocardiography when compared with LGE-negative patients (30.3 ± 7.2 mm Hg vs 14.7 ± 3.6 mm Hg, p = 0.049). They were also more likely to have LV hypertrophy. Patients with LGE were 10 times more likely to need aortic valve replacement within 1 year of the CMR study than did patients without LGE (55% vs 5.5%, p = 0.0028). In conclusion, evaluation of LGE by CMR as a marker of LV myocardial fibrosis can have additional prognostic value when evaluating patients with aortic stenosis secondary to BAV. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Diagnostic and Prognostic Significance of Ki-67 Immunohistochemical Expression in Surface Epithelial Ovarian Carcinoma

    PubMed Central

    Krishna, Shruthi Mysore; Vimala, Manjunath Gubbanna

    2017-01-01

    Introduction The Surface Epithelial Ovarian Carcinoma (SEOC) at the moment of diagnosis, the disease is extended beyond the structures of the pelvis. Ki-67 is one of the prognostic marker which determines the growth fraction of a tumour and its over expression is associated with malignancy, tumour aggression, reserved prognosis and metastasis. Aim To evaluate the proliferative activity using Ki-67 immuno-staining in SEOC and to correlate with histological subtype, grade, Federation of Gynecology and Obstetrics (FIGO) stage, CA125 levels for diagnostic and prognostic purpose. Materials and Methods The study was conducted in JSS Medical College and Hospital, JSS University, Mysuru. It was a descriptive cross-sectional study involving 40 cases of SEOC over a period of two years. The proliferation expression related to Ki-67 antigen was evaluated by immunohistochemical monoclonal MIB-1 antibody. In each case, the Ki-67 labeling index (Ki-67 LI) was articulated as percentage of positively stained cells using high power objective of the microscope (x400). Results Among the 40 carcinomas, 26 were serous, five mucinous, four each of clear cell and undifferentiated and one transitional cell carcinoma. A total of 75% were high grade tumours. High Ki-67 LI was associated with high grade tumours (69.9%), high grade serous tumours (65.34%) and advanced FIGO staging (70.6%) with the p-value of <0.001. CA 125 levels did not have a significant correlation with Ki-67 LI. Conclusion Ki-67 is an exceptionally a cost effective marker to determine the growth fraction of a tumour cell population. In SEOC histological grade and FIGO stage when combined with Ki-67 LI in histopathology report would help in diagnostic differentiation of subtypes, prognostication, deciding the need for adjuvant chemotherapy and in predicting survival analysis. PMID:28384868

  16. Diagnostic and Prognostic Significance of Ki-67 Immunohistochemical Expression in Surface Epithelial Ovarian Carcinoma.

    PubMed

    Mahadevappa, Asha; Krishna, Shruthi Mysore; Vimala, Manjunath Gubbanna

    2017-02-01

    The Surface Epithelial Ovarian Carcinoma (SEOC) at the moment of diagnosis, the disease is extended beyond the structures of the pelvis. Ki-67 is one of the prognostic marker which determines the growth fraction of a tumour and its over expression is associated with malignancy, tumour aggression, reserved prognosis and metastasis. To evaluate the proliferative activity using Ki-67 immuno-staining in SEOC and to correlate with histological subtype, grade, Federation of Gynecology and Obstetrics (FIGO) stage, CA125 levels for diagnostic and prognostic purpose. The study was conducted in JSS Medical College and Hospital, JSS University, Mysuru. It was a descriptive cross-sectional study involving 40 cases of SEOC over a period of two years. The proliferation expression related to Ki-67 antigen was evaluated by immunohistochemical monoclonal MIB-1 antibody. In each case, the Ki-67 labeling index (Ki-67 LI) was articulated as percentage of positively stained cells using high power objective of the microscope (x400). Among the 40 carcinomas, 26 were serous, five mucinous, four each of clear cell and undifferentiated and one transitional cell carcinoma. A total of 75% were high grade tumours. High Ki-67 LI was associated with high grade tumours (69.9%), high grade serous tumours (65.34%) and advanced FIGO staging (70.6%) with the p-value of <0.001. CA 125 levels did not have a significant correlation with Ki-67 LI. Ki-67 is an exceptionally a cost effective marker to determine the growth fraction of a tumour cell population. In SEOC histological grade and FIGO stage when combined with Ki-67 LI in histopathology report would help in diagnostic differentiation of subtypes, prognostication, deciding the need for adjuvant chemotherapy and in predicting survival analysis.

  17. Prognostic significance of the bcl-2 apoptotic family of proteins in primary and recurrent cervical cancer.

    PubMed Central

    Crawford, R. A.; Caldwell, C.; Iles, R. K.; Lowe, D.; Shepherd, J. H.; Chard, T.

    1998-01-01

    bcl-2 is one of a family of genes that control the apoptotic threshold of a cell. bcl-2 protein and its anti-apoptotic homologue, mcl-1, with the pro-apoptotic protein, bax, are thought to function by forming homo- and heterotypic dimers that then control the progression to apoptosis. p53 is also involved as a down-regulator of bcl-2 and a promoter of bax. To determine the effect of these apoptotic mechanisms, we used immunohistochemistry to determine the prognostic significance of the expression of bcl-2, mcl-1, bax and p53 in primary and recurrent cervical cancer. Tissues from 46 patients with primary cervical cancer and 28 women with recurrent carcinoma were stained for bcl-2, mcl-1, bax and p53. Kaplan-Meier survival analysis was performed using the log-rank test for differences between groups. In the primary disease group, positive staining for bcl-2 was associated with a better 5-year survival (bcl-2 +ve, 84% vs bcl-2 -ve, 53%, P = 0.03). Positive staining for p53 was associated with a survival disadvantage (p53 +ve, 4-year survival 38% vs p53 -ve, 4-year survival 78%, P = 0.02). mcl-1 and bax staining were not useful as prognostic indicators in primary disease. No marker was prognostic in recurrent disease. Positive bcl-2 staining defines a group of patients with primary disease with a good prognosis. p53, an activator of the bax promoter, identifies a group with a worse outcome. In recurrent disease, none of the markers reflected prognosis. PMID:9683295

  18. Oncogenic function and prognostic significance of protein tyrosine phosphatase PRL-1 in hepatocellular carcinoma

    PubMed Central

    Jin, Shaowen; Wang, Kaimei; Xu, Kang; Xu, Junyao; Sun, Jian; Chu, Zhonghua; Lin, Dechen; Koeffler, Phillip H.; Wang, Jie; Yin, Dong

    2014-01-01

    Our SNP-Chip data demonstrated 7/60 (12%) hepatocellular carcinoma (HCC) patients had PRL-1 copy number amplification. However, its biological functions and signaling pathways in HCC are deficient. Here, we investigated its oncogenic function and prognostic significance in HCC. PRL-1 protein levels were examined in 167 HCC samples by immunohistochemisty (IHC). The relationship of PRL-1 expression and clinicopathological features was assessed by correlation, Kaplan-Meier and Cox regression analyses. The oncogenic function of PRL-1 in HCC cells and its underlying mechanism were investigated by ectopic overexpression and knockdown model. PRL-1 levels in primary HCC and metastatic intravascular cancer thrombus were also determined by IHC. PRL-1 levels were frequently elevated in HCC tissues (81%), and elevated expression of PRL-1 was significantly associated with more aggressive phenotype and poorer prognosis in HCC patients (p<0.05). Ectopic overexpression of PRL-1 markedly enhanced HCC cells migration and invasion. Furthermore, the oncogenic functions of PRL-1 were mediated by PI3K/AKT/GSK3β signaling pathway through inhibiting E-cadherin expression. Finally, PRL-1 protein levels in metastatic cancer thrombus were higher than that in primary HCC tissues (p<0.05). These data highlight the oncogenic function of PRL-1 in HCC invasion and metastasis implicating PRL-1 as a potential prognostic marker as well as therapeutic target in HCC. PMID:25003523

  19. Prognostic significance of p16/cdkn2a loss in pleural malignant mesotheliomas.

    PubMed

    Dacic, Sanja; Kothmaier, Hannelore; Land, Stephanie; Shuai, Yongli; Halbwedl, Iris; Morbini, Patrizia; Murer, Bruno; Comin, Camilla; Galateau-Salle, Françoise; Demirag, Funda; Zeren, Handan; Attanoos, Richard; Gibbs, Alan; Cagle, Philip; Popper, Helmut

    2008-12-01

    Homozygous deletion of p16/CDKN2A is the most common genetic abnormality in malignant mesotheliomas. The aim of this study was to determine prognostic significance of p16/CDKN2A loss in malignant pleural mesotheliomas (MPM) as defined by immunohistochemistry and fluorescence in situ hybridization (FISH). High-density tissue microarrays were constructed from archival formalin-fixed paraffin-embedded samples of 48 MPM. Long survival (LS) was defined as survival greater than 3 years from the time of diagnosis, and short survival was defined as less than 3 years from the time of diagnosis. Both loss of p16 protein expression by immunohistochemistry and homozygous deletion of p16 by FISH were associated with adverse prognosis. Female gender, positive p16 immunoexpression, and lack of p16/CDKN2A deletion significantly predicted the survival for the LS group. Statistical analysis showed a very strong correlation of immunohistochemistry and FISH data. Cases positive for p16 immunoexpression and negative for 9p21 deletion showed the best survival time. Our study is the first to demonstrate decreased frequency of homozygous deletion of 9p21 and loss of p16 immunoreactivity in pleural mesotheliomas from patients with long-term survival of greater than 3 years in contrast to patients with rapidly fatal mesotheliomas. A possible implementation of these tests into preoperative prognostication of MPM and therapeutic decisions should be considered.

  20. Histopathological Significance and Prognostic Impact of Tumor Budding in Colorectal Cancer.

    PubMed

    Mehta, Anurag; Goswami, Malini; Sinha, Rupal

    2017-03-01

    Colorectal cancer (CRC) is a heterogeneous disease with complex etiology. New prognostic factors for this group of disease need to be investigated. This study evaluated the histopathological significance and prognostic impact of tumor budding in CRC. A total of 60 treatment naive consecutive patients undergoing surgical resection for CRC during the period of January 2011 to December 2013 were included in the study. Details of each patient related to their demographic and tumor profile were recorded. Pan Cytokeratin immunohistochemistry was applied on chosen sections and tumor budding was assessed. The most frequent site of involvement was rectosigmoid and sigmoid colon (31.6%). The majority of the cases were moderately differentiated (75%) in morphology, and showed tumor invasion into the pericolic/subserosal fat (66.6%), and were stage III (38.3%). Nodal involvement was present in 50% cases. Correlations between tumor budding and nodal involvement (p-value 0.039) and AJCC stage (p-value 0.021) were found to be statistically significant. Tumor budding may be a promising and powerful predictor of lymphnodal metastasis and a higher stage of tumor and can be used as a marker for assessing the aggressiveness of CRC. Routine hemotoxylin-eosin staining supported by cytokeratin immunostain can aid in the grading of tumor budding in CRC. © 2017 by the Association of Clinical Scientists, Inc.

  1. Oncogenic function and prognostic significance of protein tyrosine phosphatase PRL-1 in hepatocellular carcinoma.

    PubMed

    Jin, Shaowen; Wang, Kaimei; Xu, Kang; Xu, Junyao; Sun, Jian; Chu, Zhonghua; Lin, Dechen; Koeffler, Phillip H; Wang, Jie; Yin, Dong

    2014-06-15

    Our SNP-Chip data demonstrated 7/60 (12%) hepatocellular carcinoma (HCC) patients had PRL-1 copy number amplification. However, its biological functions and signaling pathways in HCC are deficient. Here, we investigated its oncogenic function and prognostic significance in HCC. PRL-1 protein levels were examined in 167 HCC samples by immunohistochemisty (IHC). The relationship of PRL-1 expression and clinicopathological features was assessed by correlation, Kaplan-Meier and Cox regression analyses. The oncogenic function of PRL-1 in HCC cells and its underlying mechanism were investigated by ectopic overexpression and knockdown model. PRL-1 levels in primary HCC and metastatic intravascular cancer thrombus were also determined by IHC. PRL-1 levels were frequently elevated in HCC tissues (81%), and elevated expression of PRL-1 was significantly associated with more aggressive phenotype and poorer prognosis in HCC patients (p<0.05). Ectopic overexpression of PRL-1 markedly enhanced HCC cells migration and invasion. Furthermore, the oncogenic functions of PRL-1 were mediated by PI3K/AKT/GSK3β signaling pathway through inhibiting E-cadherin expression. Finally, PRL-1 protein levels in metastatic cancer thrombus were higher than that in primary HCC tissues (p<0.05). These data highlight the oncogenic function of PRL-1 in HCC invasion and metastasis implicating PRL-1 as a potential prognostic marker as well as therapeutic target in HCC.

  2. Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance.

    PubMed

    Yu, Tianjian; Di, Genhong

    2017-06-01

    Breast cancer has been shown to live in the tumor microenvironment, which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells. Diverse components of the breast cancer microenvironment, such as suppressive immune cells, re-programmed fibroblast cells, altered extracellular matrix (ECM) and certain soluble factors, synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis. Among these components, stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways, whereas the ECM features biochemical and biomechanical changes. However, triple-negative breast cancer (TNBC), the most aggressive subtype of this disease that lacks effective therapies available for other subtypes, is considered to feature a unique microenvironment distinct from that of other subtypes, especially compared to Luminal A subtype. Because these changes are now considered to significantly impact breast cancer development and progression, these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC. In this review, we focus on the composition of the TNBC microenvironment, concomitant distinct biological alteration, specific interplay between various cell types and TNBC cells, and the prognostic implications of these findings.

  3. Prognostic significance of c-erbB-2 expression in node negative breast cancer.

    PubMed Central

    Bianchi, S.; Paglierani, M.; Zampi, G.; Cardona, G.; Cataliotti, L.; Bonardi, R.; Ciatto, S.

    1993-01-01

    The prognostic value of c-erbB-2 oncogene expression was studied retrospectively in a consecutive series of 230 node negative breast cancers, followed-up for at least 7 years after primary treatment. The expression of c-erbB-2 oncoprotein was determined on formalin-fixed paraffin-embedded tissue, using a monoclonal anti-c-erbB-2 antibody by the avidin-biotin immunoperoxidase method. Positive immunostaining was observed in 20.9% of cases, whereas strong diffuse positivity was recorded only in 8.7% of cases. C-erbB-2 gene product showed no association to T category or nuclear grade. A significant association of c-erbB-2 expression to prognosis was observed only for cases showing a strong diffuse immunostaining, but such an association was no longer statistically significant at multivariate analysis adjusting for other prognostic factors such as T category and nuclear grading. C-erbB-2 expression is of no value to predict the clinical course of node negative patients in the current practice. Images Figure 1 Figure 2 PMID:8094977

  4. Role of tumor microenvironment in triple-negative breast cancer and its prognostic significance

    PubMed Central

    Yu, Tianjian; Di, Genhong

    2017-01-01

    Breast cancer has been shown to live in the tumor microenvironment, which consists of not only breast cancer cells themselves but also a significant amount of pathophysiologically altered surrounding stroma and cells. Diverse components of the breast cancer microenvironment, such as suppressive immune cells, re-programmed fibroblast cells, altered extracellular matrix (ECM) and certain soluble factors, synergistically impede an effective anti-tumor response and promote breast cancer progression and metastasis. Among these components, stromal cells in the breast cancer microenvironment are characterized by molecular alterations and aberrant signaling pathways, whereas the ECM features biochemical and biomechanical changes. However, triple-negative breast cancer (TNBC), the most aggressive subtype of this disease that lacks effective therapies available for other subtypes, is considered to feature a unique microenvironment distinct from that of other subtypes, especially compared to Luminal A subtype. Because these changes are now considered to significantly impact breast cancer development and progression, these unique alterations may serve as promising prognostic factors of clinical outcome or potential therapeutic targets for the treatment of TNBC. In this review, we focus on the composition of the TNBC microenvironment, concomitant distinct biological alteration, specific interplay between various cell types and TNBC cells, and the prognostic implications of these findings. PMID:28729775

  5. Prognostic significance of tumor infiltrating immune cells in oral squamous cell carcinoma.

    PubMed

    Fang, Juan; Li, Xiaoxu; Ma, Da; Liu, Xiangqi; Chen, Yichen; Wang, Yun; Lui, Vivian Wai Yan; Xia, Juan; Cheng, Bin; Wang, Zhi

    2017-05-26

    Prognostic factors aid in the stratification and treatment of cancer. This study evaluated prognostic importance of tumor infiltrating immune cell in patients with oral squamous cell carcinoma. Profiles of infiltrating immune cells and clinicopathological data were available for 78 OSCC patients with a median follow-up of 48 months. The infiltrating intensity of CD8, CD4, T-bet, CD68 and CD57 positive cells were assessed by immunohistochemistry. Chi-square test was used to compare immune markers expression and clinicopathological parameters. Univariate and multivariate COX proportional hazard models were used to assess the prognostic discriminator power of immune cells. The predictive potential of immune cells for survival of OSCC patients was determined using ROC and AUC. The mean value of CD8, CD4, T-bet, CD68 and CD57 expression were 28.99, 62.06, 8.97, 21.25 and 15.75 cells per high-power field respectively. The patient cohort was separated into low and high expression groups by the mean value. Higher CD8 expression was associated with no regional lymph node metastasis (p = 0.033). Patients with more abundant stroma CD57(+) cells showed no metastasis into regional lymph node (p = 0.005), and early clinical stage (p = 0.016). The univariate COX regression analyses showed that no lymph node involvement (p < 0.001), early clinical stage (TNM staging I/II vs III/IV, p = 0.007), higher CD8 and CD57 expression (p < 0.001) were all positively correlated with longer overall survival. Multivariate COX regression analysis showed that no lymph node involvement (p = 0.008), higher CD8 (p = 0.03) and CD57 (p < 0.001) expression could be independent prognostic indicators of better survival. None of CD4, T-bet or CD68 was associated with survival in ether univariate or multivariate analysis. ROC and AUC showed that the predictive accuracy of CD8 and CD57 were all superior compared with TNM staging. CD57 (AUC = 0.868; 95% CI, 0.785-0.950) and CD8 (AUC

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

    PubMed

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

    2012-10-01

    We performed a comparative proteomic analysis of protein expression profiles in 4 cholangiocarcinoma cell lines: K100, M156, M213, and M139. The H69 biliary cell line was used as a control. Peroxiredoxin 1 and ezrin-radixin-moesin-binding phosphoprotein 50 were selected for further validation by immunohistochemistry using a cholangiocarcinoma tissue microarray (n = 301) to assess their prognostic value in this cancer. Both peroxiredoxin 1 and ezrin-radixin-moesin-binding phosphoprotein 50 were overexpressed in cholangiocarcinoma tissues compared with normal liver tissues. Of the 301 cholangiocarcinoma cases, overexpression of peroxiredoxin 1 in 103 (34.3%) was associated with an age-related effect in young patients (P = .011) and the absence of cholangiocarcinoma in lymphatic vessels and perineural tissues (P = .004 and P = .037, respectively). Expression of radixin-moesin-binding phosphoprotein 50 correlated with histopathologic type, with 180 (59.8%) of moderately or poorly differentiated tumors (P = .039) being higher, and was associated with the presence of cholangiocarcinoma in lymphatic and vascular vessels (P < .001 and P < .001, respectively). The high expression of radixin-moesin-binding phosphoprotein 50 and the low expression of peroxiredoxin 1 correlated with reduced survival by univariate analysis (P = .017 and P = .048, respectively). Moreover, the impact of peroxiredoxin 1 and radixin-moesin-binding phosphoprotein 50 expression on patient survival was an independent predictor in multivariate analyses (P = .004 and P = .025, respectively). Therefore, altered expression of peroxiredoxin 1 and radixin-moesin-binding phosphoprotein 50 may be used as prognostic markers in cholangiocarcinoma.

  7. Performance status as a significant prognostic predictor in patients with urothelial carcinoma of the bladder who underwent radical cystectomy.

    PubMed

    Hinata, Nobuyuki; Miyake, Hideaki; Miyazaki, Akira; Nishikawa, Masatomo; Tei, Hiromoto; Fujisawa, Masato

    2015-08-01

    To assess the significance of performance status as a prognostic factor after radical cystectomy for urothelial carcinoma of the bladder. The present study included 730 consecutive patients with urothelial carcinoma of the bladder who underwent radical cystectomy. Clinicopathological outcomes in these patients were analyzed focusing on the impact of performance status, which was assessed using the Karnofsky Performance Status scale before surgery. Patients were classified into groups with Karnofsky Performance Status ≥90 and ≤80. A total of 561 (76.8%) and 169 (23.2%) patients were judged to have Karnofsky Performance Status ≥90 and ≤80, respectively. During a mean of 52.0 months, disease recurrence and mortality occurred in 257 (35.2%) and 249 (34.1%) patients, respectively, and the 5-year recurrence-free and overall survival rates were 64.1 and 65.3%, respectively. There were significant differences in age, hemoglobin, albumin, estimated glomerular filtration rate, pathological T stage and nodal involvement between the Karnofsky Performance Status ≥90 and ≤80 groups. Multivariate analysis showed independent impacts of Karnofsky Performance Status, pathological T stage, nodal involvement and lymphovascular invasion on recurrence-free survival, as well as independent impacts of Karnofsky Performance Status, age, body mass index, hemoglobin, pathological T stage, nodal involvement and lymphovascular invasion on overall survival. The results suggest a significant association between impaired performance status and unfavorable prognosis in patients with urothelial carcinoma of the bladder undergoing radical cystectomy. © 2015 The Japanese Urological Association.

  8. Prognostic significance of Notch ligands in patients with non-small cell lung cancer.

    PubMed

    Pancewicz-Wojtkiewicz, Joanna; Eljaszewicz, Andrzej; Kowalczuk, Oksana; Niklinska, Wieslawa; Charkiewicz, Radoslaw; Kozłowski, Miroslaw; Miasko, Agnieszka; Moniuszko, Marcin

    2017-01-01

    The Notch signaling pathway is deregulated in numerous solid types of cancer including non-small cell lung cancer (NSCLC). However, the profile of Notch ligand expression remains unclear. Therefore, the present study aimed to determine the profile of Notch ligands in NSCLC patients and to investigate whether quantitative assessment of Notch ligand expression may have prognostic significance in NSCLC patients. The study was performed in 61 pairs of tumor and matched unaffected lung tissue specimens obtained from patients with various stages of NSCLC, which were analyzed by reverse transcription-polymerase chain reaction. The marked expression levels of certain analyzed genes were detected in NSCLC samples and in noncancerous lung samples. Of the five Notch ligands, jagged 1 (Jag1), jagged 2, delta-like protein 1 and delta-like protein 4 were expressed in the majority of tissues, but their expression levels were reduced in NSCLC when compared with noncancerous lung tissue (P<0.001). Delta-like protein 3 expression was consistently low and was observed only in 21/61 tumor tissue samples. Taken together, Notch ligands are expressed in NSCLC. However, the expression level is reduced when compared to noncancerous tissue. Furthermore, the present study revealed that quantitative assessment of Jag1 expression in NSCLC may improve prognostication of patient survival.

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

    PubMed

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

    2017-04-01

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

  10. Prognostic significance of PD-L1 and PD-L2 in breast cancer.

    PubMed

    Baptista, Mauricio Z; Sarian, Luis Otavio; Derchain, Sophie F M; Pinto, Glauce A; Vassallo, José

    2016-01-01

    PD-L1 and PD-L2 constitute an important antitumor immune response. In breast cancer, their prognostic value is still to be defined. In this study, we investigate the correlation between PD-L1 and PD-L2 protein expressions with clinical and pathologic features and disease-free survival and overall survival. To assess PD-L1 and PD-L2 expressions, we conducted immunohistochemistry studies using a breast cancer tissue microarray encompassing a total of 192 breast cancer cases, stages I, II, and III, with detailed clinical and outcome data. PD-L1 expression was present in 56.6% (107/189), and PD-L2 expression was identified in 50.8% (97/191) of breast cancer cases. Younger age at diagnosis, lymph node positivity, negative estrogen receptor, and recurrence at distant sites were all associated with both PD-L1 and PD-L2 expressions. The presence of larger tumors was associated only with PD-L1 expression. In our study, PD-L1 expression was significantly associated with better overall survival (P = .04) in breast cancer patients. Despite its association with poor clinical and pathologic features, PD-L1 expression emerges as a positive prognostic biomarker in breast cancer. This survival result might be due to the presence of a strong antitumor immune response leading to PD-L1 expression. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Immunohistochemically detectable p53 and mdm-2 oncoprotein expression in colorectal carcinoma: prognostic significance

    PubMed Central

    Öfner, D; Maier, H; Riedmann, B; Holzberger, P; Nogler, M; Tötsch, M; Bankfalvi, A; Winde, G; Böcker, W; Schmid, K W

    1995-01-01

    Aims—To investigate the correlation between the expression of the p53 and mdm-2 oncoproteins and to assess their prognostic value in colorectal cancer. Methods—Using a polyclonal (CM1) and a monoclonal antibody directed against p53 and mdm-2, respectively, these oncoproteins were stained immunohistochemically in 109 colorectal adenocarcinomas. Results—p53 was detected in less than 10% of tumour cells in 11 of 109 adenocarcinomas, in 10-50% of tumour cells, in 17 of 109 adenocarcinomas, and in more than 50% of tumour cells in 32 of 109 adenocarcinomas. Expression of mdm-2 was detected in 22 of 109 (20%) cases investigated, of which 19 showed concomitant p53 expression. In most cases mdm-2 immunoreactivity was strongly associated with a small proportion of p53 positive tumour cells. Both p53 and mdm-2 expression lacked statistical significance when correlated with common staging and grading parameters. Conclusions—Detection of p53 and mdm-2 oncoprotein expression, detected using immunohistochemistry, is of no prognostic value in colorectal cancer. However, the close correlation between mdm-2 immunoreactivity and the proportion of p53 positive cells provides further evidence that the mdm-2 gene product interacts with p53 protein. PMID:16695968

  12. Diagnostic and prognostic significance of inflammatory markers in lung cancer-associated pleural effusions.

    PubMed

    Kotyza, Jaromir; Havel, David; Vrzalová, Jindra; Kulda, Vlastimil; Pesek, Milos

    2010-01-01

    Besides massive expression in inflammatory pleural effusions, inflammatory markers are also present in cancerinduced pleural effusions. Recent advances in cancer biology point to a role of inflammatory signaling in cancer and encourage reconsidering the diagnostic and prognostic value of inflammatory markers. Here an attempt was made to relate protein levels of inflammatory markers to underlying malignant processes in the pleural space. Pleural effusions from lung cancer patients (n=116) were subjected to a multifactorial analysis covering 13 inflammatory markers. The composition of tumor-associated effusions was compared with that of parainflammatory pleural effusions (n=30), transudates (n=18), and serum values, and evaluated in relation to cancer origin, histology, cytology, pleural involvement, treatment history, and survival time. Inflammatory markers were significantly expressed in pleural effusions of paraneoplastic origin when compared to transudates and most serum levels. Values in pleura-invading and metastatic tumor-associated effusions were typically higher than those of other tumors. Many markers correlated negatively with survival, most prominently IL-8 (r=-0.36, p=0.001) and VEGF (r=-0.35, p=0.001). It appears that most inflammatory markers are highly expressed in tumor-associated pleural effusions, reflecting to some extent tumor origin and localization. Despite the lower efficacy of inflammatory markers in the differentiation between exudative pleural effusions, some inflammatory markers may represent potential prognostic markers of malignant processes in the pleural space.

  13. [Prognostic significance of serum iron level, hemoglobin and rheumatoid factor titre in rheumatoid arthritis].

    PubMed

    Fischer, H; Häntzschel, H; Winiecki, P; Otto, W

    1977-02-01

    On the basis of the results of a five-year examination of the course on 120 patients with rheumatoid arthritis the authors adopt a definite attitude to the prognostic significance of hypersiderinaemia, anaemia and height of the titre of the rheumatoid factor. With the help of the chi2-test and the rank correlation after Spearman the statistical relations to stage, activity, clinical and radiological progressing as well as to the number of the affected joints were examined. In seropositive patients we found a correlation of the titre of rheumatoid factor and stage. Furthermore a clear correlation existed to clinical and radiological progressing as well as to the number of the affected joints. Early highly positive titres of the rheumatoid factor as an expression of high immunologic activity suggest an unfavourable prognosis in the majority of cases. Constant anaemia and hyposiderinaemia as symptoms of a high basis activity of the disease also showed close relations to the progressing. From this result indications for the early use of important therapeutic measures. For the prognostic judgement of the course of the disease of rheumatoid arthritis it is necessary to have at disposal further methodically simply determinable parameters for the recognition of the basis activity and the immunologic activity.

  14. Endoscopy-verified occult subependymal dissemination of glioblastoma and brain metastasis undetected by MRI: prognostic significance

    PubMed Central

    Iacoangeli, Maurizio; Di Rienzo, Alessandro; Colasanti, Roberto; Zizzi, Antonio; Gladi, Maurizio; Alvaro, Lorenzo; Nocchi, Niccolò; Di Somma, Lucia Giovanna Maria; Scarpelli, Marina; Scerrati, Massimo

    2012-01-01

    Although various prognostic indices exist for patients with malignant brain tumors, the prognostic significance of the subependymal spread of intracranial tumors is still a matter of debate. In this paper, we report the cases of two intraventricular lesions, a recurrent glioblastoma multiforme (GBM) and a brain metastasis, each successfully treated with a neuroendoscopic approach. Thanks to this minimally invasive approach, we achieved good therapeutic results: we obtained a histological diagnosis; we controlled intracranial hypertension by treating the associated hydrocephalus and, above all, compared with a microsurgical approach, we reduced the risks related to dissection and brain retraction. Moreover, in both cases, neuroendoscopy enabled us to identify an initial, precocious subependymal tumor spreading below the threshold of magnetic resonance imaging (MRI) detection. This finding, undetected in pre-operative MRI scans, was then evident during follow-up neuroimaging studies. In light of these data, a neuroendoscopic approach might play a leading role in better defining the prognosis and optimally tailored management protocols for GBM and brain metastasis. PMID:23271915

  15. Prognostic significance of smoking in patients with acute ischemic stroke within 3 months of onset.

    PubMed

    Kumagai, Naoko; Origasa, Hideki; Nagao, Takehiko; Takekawa, Hidehiro; Okuhara, Yoshiyasu; Yamaguchi, Takenori

    2013-08-01

    Various factors that have been implicated in recovery after the acute phase of stroke have not been well evaluated. To identify prognostic factors affecting outcomes at 90 days after stroke from the viewpoint of recovery patterns, we enrolled 660 patients from the Edaravone and Argatroban Stroke Therapy for Acute Ischemic Stroke study database. Fourteen groups of patients were identified based on an analysis of their recovery patterns according to changes in their National Institutes of Health Stroke Scale scores during the first 21 days. These groups were then divided into 2 groups: favorable recovery trend (patterns 1-3; n = 486) and poor recovery trend (patterns 4-14; n = 174). Patterns with >80% of the patients experiencing a favorable outcome (National Institutes of Health Stroke Scale score of ≤ 4 at 90 days) were defined as the favorable recovery trend group, whereas patterns that included ≤ 80% favorable outcomes were defined as the poor recovery trend group. Using the poor recovery trend group, logistic regression analysis found that after controlling for covariates, lower scores at admission, fewer ischemic lesions, and nonsmoking were significant prognostic factors for a favorable outcome at 90 days. Based on a detailed analysis of the relationship between recovery patterns after stroke and clinical outcomes in the chronic stage of stroke, smoking cessation may improve the prognosis of patients after stroke. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Reduced high-density lipoprotein cholesterol: A valuable, independent prognostic marker in peripheral arterial disease.

    PubMed

    Martinez-Aguilar, Esther; Orbe, Josune; Fernández-Montero, Alejandro; Fernández-Alonso, Sebastián; Rodríguez, Jose A; Fernández-Alonso, Leopoldo; Páramo, Jose A; Roncal, Carmen

    2017-06-27

    The prognosis of patients with peripheral arterial disease (PAD) is characterized by an exceptionally high risk for myocardial infarction, ischemic stroke, and death; however, studies in search of new prognostic biomarkers in PAD are scarce. Even though low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with higher risk of cardiovascular (CV) complications and death in different atherosclerotic diseases, recent epidemiologic studies have challenged its prognostic utility. The aim of this study was to test the predictive value of HDL-C as a risk factor for ischemic events or death in symptomatic PAD patients. Clinical and demographic parameters of 254 symptomatic PAD patients were recorded. Amputation, ischemic coronary disease, cerebrovascular disease, and all-cause mortality were recorded during a mean follow-up of 2.7 years. Multivariate analyses showed that disease severity (critical limb ischemia) was significantly reduced in patients with normal HDL-C levels compared with the group with low HDL-C levels (multivariate analysis odds ratio, 0.09; 95% confidence interval [CI], 0.03-0.24). A decreased risk for mortality (hazard ratio, 0.46; 95% CI, 0.21-0.99) and major adverse CV events (hazard ratio, 0.38; 95% CI, 0.16-0.86) was also found in patients with normal vs reduced levels of HDL-C in both Cox proportional hazards models and Kaplan-Meier estimates, after adjustment for confounding factors. Reduced HDL-C levels were significantly associated with higher risk for development of CV complications as well as with mortality in PAD patients. These findings highlight the usefulness of this simple test for early identification of PAD patients at high risk for development of major CV events. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  17. 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

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

    PubMed

    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

    2014-09-01

    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. Copyright© Ferrata Storti Foundation.

  19. 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

  20. Prognostic significance of ATM and TP53 deletions in Chinese patients with chronic lymphocytic leukemia.

    PubMed

    Xu, Wei; Li, Jian-Yong; Wu, Yu-Jie; Yu, Hui; Shen, Qiu-Dan; Li, Li; Fan, Lei; Qiu, Hong-Xia

    2008-07-01

    Chronic lymphocytic leukemia (CLL) is the most common adult form of leukemia in the Western world, however, infrequent in the Eastern. It shows a remarkable heterogeneity, with some patients having an almost normal lifespan, others surviving only several years after diagnosis despite intensive therapy. To prospectively explore the prognostic significance of ATM and TP53 deletions in Chinese patients with CLL, interphase fluorescence in situ hybridization (FISH) and probes of LSI ATM and LSI p53 were used to detect ATM and TP53 deletions in 95 patients with CLL. ATM and TP53 deletions and their association with some other prognostic factors such as Binet stage, lymphocyte count in peripheral blood, serum lactate dehydrogenase (LDH), beta2-microglobulin (beta2-MG), CD38 and ZAP-70 expressions were analyzed. The Kaplan-Meier method was used to construct survival curves, and results were compared using the log-rank test. Univariate and multivariate Cox regression analyses were used to assess associations between survival time and potential risk factors. Out of the 95 patients with CLL, ATM gene deletion was found in 9 (9.5%) patients, TP53 gene deletion in 16 (16.8%) cases. There were no significant differences between ATM or TP53 deletion and clinical parameters of sex, age, Binet stage, lymphocyte count, LDH, beta2-MG or ZAP-70 expression. However, the frequency of ATM and TP53 deletions were obviously higher in CD38-positive group than in CD38-negative group (P=0.001 and P=0.047, respectively). Among 41 patients received treatment with fludarabine and cyclophosphamide, there were nine patients with TP53 or ATM deletion, and no patient with these cytogenetic abnormalities achieved complete response (CR). Survival analysis showed that the patients with TP53 deletion had significantly shorter survival times than the patients without TP53 deletion. There was no evidence of important association between outcome and ATM gene deletion. Serum levels of LDH and beta2-MG, CD

  1. Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol.

    PubMed

    Van der Velden, V H J; Corral, L; Valsecchi, M G; Jansen, M W J C; De Lorenzo, P; Cazzaniga, G; Panzer-Grümayer, E R; Schrappe, M; Schrauder, A; Meyer, C; Marschalek, R; Nigro, L L; Metzler, M; Basso, G; Mann, G; Den Boer, M L; Biondi, A; Pieters, R; Van Dongen, J J M

    2009-06-01

    Acute lymphoblastic leukemia (ALL) in infants younger than 1 year is a rare but relatively homogeneous disease ( approximately 80% MLL gene rearranged, approximately 70% CD10-negative) when compared with childhood and adult ALL. Several studies in children and adults with ALL have shown that minimal residual disease (MRD) status is a strong and independent prognostic factor. We therefore evaluated the prognostic significance of MRD in infant ALL. Ninety-nine infant patients treated according to the Interfant-99 protocol were included in this study. MRD was analyzed by real-time quantitative PCR analysis of rearranged immunoglobulin genes, T-cell receptor genes and MLL genes at various time points (TP) during therapy. Higher MRD levels at the end of induction (TP2) and consolidation (TP3) were significantly associated with lower disease-free survival. Combined MRD information at TP2 and TP3 allowed recognition of three patients groups that significantly differed in outcome. All MRD-high-risk patients (MRD levels > or =10(-4) at TP3; 26% of patients) relapsed. MRD-low-risk patients (MRD level <10(-4) at both TP2 and TP3) constituted 44% of patients and showed a relapse-rate of only 13%, whereas remaining patients (MRD-medium-risk patients; 30% of patients) had a relapse rate of 31%. Comparison between the current Interfant-06 stratification at diagnosis and the here presented MRD-based stratification showed that both stratifications recognized different subgroups of patients. These data indicate that MRD diagnostics has added value for recognition of risk groups in infant ALL and that MRD diagnostics can be used for treatment intervention in infant ALL as well.

  2. Prognostic Significance of Initial Serum Albumin and 24 Hour Daily Protein Excretion before Treatment in Multiple Myeloma.

    PubMed

    Chen, Jia-Hong; Hsu, Shun-Neng; Huang, Tzu-Chuan; Wu, Yi-Ying; Lin, Chin; Chang, Ping-Ying; Chen, Yeu-Chin; Ho, Ching-Liang

    2015-01-01

    Renal failure is a common morbidity in multiple myeloma (MM). Although proteinuria has been increasingly reported in malignancies, it is not routinely used to refine risk estimates of survival outcomes in patients with MM. Here we aimed to investigate initial serum albumin and 24-hour daily protein excretion (24-h DPE) before treatment as prognostic factors in patients with MM. We conducted a retrospective analysis of 102 patients with myeloma who were ineligible for haematopoietic stem cell transplantation between October 2000 and December 2012. Initial proteinuria was assessed before treatment by quantitative analysis of 24-hour urine samples. The demographic and laboratory characteristics, survival outcome, and significance of pre-treatment 24-h DPE and albumin in the new staging system of MM were analyzed. Pre-treatment proteinuria (>300 mg/day) was present in 66 patients (64.7%). The optimal cut-off value of 24-h DPE before treatment was 500 mg/day. Analysis of the time-dependent area under the curve showed that the serum albumin and 24-h DPE before treatment were better than 24-h creatinine clearance rate and β2-microglobulin. A subgroup analysis showed that an initial excess proteinuria (24-h DPE ≥ 500 mg) was associated with poor survival status (17.51 vs. 34.24 months, p = 0.002). Furthermore, initial serum albumin was an independent risk factor on multivariate analysis (<2.8 vs. ≥ 2.8, hazard ratio = 0.486, p = 0.029). Using the A-DPE staging system, there was a significant survival difference among patients with stage I, II, and III MM (p < 0.001). Initial serum albumin and 24-h DPE before treatment showed significant prognostic factors in patients with MM, and the new A-DPE staging system may be utilized instead of the International Staging System. Its efficacy should be evaluated by further large prospective studies.

  3. Immunohistochemical and Molecular Characteristics with Prognostic Significance in Diffuse Large B-Cell Lymphoma

    PubMed Central

    Bellas, Carmen; García, Diego; Vicente, Yolanda; Kilany, Linah; Abraira, Victor; Navarro, Belen; Provencio, Mariano; Martín, Paloma

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with marked biologic heterogeneity. We analyzed 100 cases of DLBCL to evaluate the prognostic value of immunohistochemical markers derived from the gene expression profiling-defined cell origin signature, including MYC, BCL2, BCL6, and FOXP1 protein expression. We also investigated genetic alterations in BCL2, BCL6, MYC and FOXP1 using fluorescence in situ hybridization and assessed their prognostic significance. BCL6 rearrangements were detected in 29% of cases, and BCL6 gene alteration (rearrangement and/or amplification) was associated with the non-germinal center B subtype (non-GCB). BCL2 translocation was associated with the GCB phenotype, and BCL2 protein expression was associated with the translocation and/or amplification of 18q21. MYC rearrangements were detected in 15% of cases, and MYC protein expression was observed in 29% of cases. FOXP1 expression, mainly of the non-GCB subtype, was demonstrated in 37% of cases. Co-expression of the MYC and BCL2 proteins, with non-GCB subtype predominance, was observed in 21% of cases. We detected an association between high FOXP1 expression and a high proliferation rate as well as a significant positive correlation between MYC overexpression and FOXP1 overexpression. MYC, BCL2 and FOXP1 expression were significant predictors of overall survival. The co-expression of MYC and BCL2 confers a poorer clinical outcome than MYC or BCL2 expression alone, whereas cases negative for both markers had the best outcomes. Our study confirms that DLBCL, characterized by the co-expression of MYC and BCL2 proteins, has a poor prognosis and establishes a significant positive correlation with MYC and FOXP1 over-expression in this entity. PMID:24887414

  4. The Prognostic Significance of Her2-Neu Over expression in Gastric Carcinomas

    PubMed Central

    Ansari, J; Chehrei, A; Amini, M; Alizade, SH; Sanei, MH

    2011-01-01

    Background Her2/neu is one of the epidermal growth factor receptors families and seems to have prognostic significance of some solid tumors. The objective of this study is to evaluate the possibility of Her2 expression in gastric cancers and the possible relationship of Her2 with tumor’s clinicopathologic parameters and also its prognostic role. Methods This study was performed on 100 cases of gastric carcinoma with stage I b to III (according to TNM staging). Survival, recurrence date of patients, grade and lymph nodes involvement were assessed. Her2/neu expression was determined by immunohistochemical method on received sample blocks. Survival of patients with or without Her2-neu expression were evaluated by Kaplan- Meier method and compared with the log-rank test followed by multivariate analysis using Cox regression. Results Seven cases were 3+ membranous Her2 reactivity, 5 cases were 2+ and13 cases were 1+; also 75% of cases demonstrated no reactivity. Regardingrelationship between tumor grade and membranous Her2 , all patients with poorly differentiated tumors were Her2 negative but patients with moderate and well differentiated tumor had 18.1% and 19.6% Her2 reactivity respectively; there were no significant difference between groups statistically(P>0.05). Median overall survival was 27.25 and 46 months in Her2 negative and her2 positive cases respectively; there were no significant difference between groups statistically as well (P>0.05). Conclusion Her2 reactivity has not relationship with tumor grade and lymph node involvement as well as tumor stage. From the other point of view no significant correlation is found between Her2 expression and disease free survival or overall survival of gastric cancer patients. PMID:26322194

  5. Human leukocyte antigen class I expression is an independent prognostic factor in advanced ovarian cancer resistant to first-line platinum chemotherapy.

    PubMed

    Shehata, M; Mukherjee, A; Deen, S; Al-Attar, A; Durrant, L G; Chan, S

    2009-10-20

    Loss of HLA class I is important in ovarian cancer prognosis but its role as a prognostic indicator in relation to therapy remains unproven. We studied the prognostic potential of this antigen and its significance in relation to platinum therapy. A total of 157 primary ovarian cancers were assessed for HLA class I immunohistochemically and linked to a comprehensive database of clinicopathological variables, treatment details, and platinum sensitivity. Tumours expressing high levels of HLA class I had significantly improved survival (P=0.044). There was a 19-month difference in the median overall survival between tumours with high and low antigen expression. HLA class I antigen expression, stage, and platinum sensitivity were independently predictive of prognosis on multivariate analysis. HLA class I antigen was shown to be expressed at higher levels in patients with good overall survival in platinum-resistant patients (P=0.042). HLA class I significantly correlated with overall survival on multivariate analyses (P=0.034). Low-level HLA class I expression is an independent prognostic indicator of poor clinical outcome in ovarian cancer. The survival advantage of patients with platinum-resistant tumours expressing high levels of HLA class I suggests that immunotherapy may be of use in these ovarian cancers resistant to standard chemotherapy.

  6. Human leukocyte antigen class I expression is an independent prognostic factor in advanced ovarian cancer resistant to first-line platinum chemotherapy

    PubMed Central

    Shehata, M; Mukherjee, A; Deen, S; Al-Attar, A; Durrant, L G; Chan, S

    2009-01-01

    Background: Loss of HLA class I is important in ovarian cancer prognosis but its role as a prognostic indicator in relation to therapy remains unproven. We studied the prognostic potential of this antigen and its significance in relation to platinum therapy. Methods: A total of 157 primary ovarian cancers were assessed for HLA class I immunohistochemically and linked to a comprehensive database of clinicopathological variables, treatment details, and platinum sensitivity. Results: Tumours expressing high levels of HLA class I had significantly improved survival (P=0.044). There was a 19-month difference in the median overall survival between tumours with high and low antigen expression. HLA class I antigen expression, stage, and platinum sensitivity were independently predictive of prognosis on multivariate analysis. HLA class I antigen was shown to be expressed at higher levels in patients with good overall survival in platinum-resistant patients (P=0.042). HLA class I significantly correlated with overall survival on multivariate analyses (P=0.034). Conclusion: Low-level HLA class I expression is an independent prognostic indicator of poor clinical outcome in ovarian cancer. The survival advantage of patients with platinum-resistant tumours expressing high levels of HLA class I suggests that immunotherapy may be of use in these ovarian cancers resistant to standard chemotherapy. PMID:19755991

  7. Hypoglycorrhachia in adults with community-acquired meningitis: etiologies and prognostic significance.

    PubMed

    Shrikanth, Vandana; Salazar, Lucrecia; Khoury, Nabil; Wootton, Susan; Hasbun, Rodrigo

    2015-10-01

    Hypoglycorrhachia (cerebrospinal fluid (CSF) glucose <45 mg/dl) has been identified as a prognostic factor in patients with meningitis. The differential diagnosis of hypoglycorrhachia and its clinical significance was analyzed in the present study. This was a retrospective study of 620 adult patients with community-acquired meningitis (CSF white blood cell count >5 × 10(6) cells/l and absence of a CSF shunt or recent neurosurgical procedure (<1 month)) at eight Memorial Hermann hospitals in Houston, Texas, from January 2005 to December 2010. An adverse clinical outcome was defined as a Glasgow outcome scale score of ≤ 4. Out of 620 patients with meningitis, 116 (19%) had hypoglycorrhachia. Etiologies of hypoglycorrhachia were idiopathic (n=40), bacterial (n=27), cryptococcal (n=26), viral (n=15), and tuberculous (n=4). Patients with hypoglycorrhachia were more likely to be immunosuppressed, have a history of intravenous drug use, and present with a vesicular or petechial rash, nausea or vomiting, nuchal rigidity, sinusitis/otitis, abnormal mental status, and focal neurological deficits compared to those patients without hypoglycorrhachia (p<0.05). Additionally, patients in the hypoglycorrhachia group had significantly higher rates of positive CSF and blood cultures, urgent treatable conditions, and abnormal cranial imaging (p<0.05). Furthermore, patients with hypoglycorrhachia had more adverse clinical outcomes (26/116 (22.4%) vs. 45/504 (8.9%); p<0.001). Hypoglycorrhachia has significant clinical and prognostic value in the evaluation of adult patients with community-acquired meningitis. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. 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.

  9. RPA classification has prognostic significance for surgically resected single brain metastasis

    SciTech Connect

    Tendulkar, Rahul D.; Liu, Stephanie W.; Barnett, Gene H.; Vogelbaum, Michael A.; Toms, Steven A.; Jin Tao; Suh, John H.

    2006-11-01

    Purpose: To retrospectively evaluate prognostic factors that correlate with overall survival among patients with a surgically resected single brain metastasis. Methods and Materials: An Institutional Review Board-approved database of Cleveland Clinic Brain Tumor Institute was queried for patients with a single brain metastasis treated by surgical resection between February 1984 and January 2004. The primary endpoint was overall survival from the date of surgery by the Kaplan-Meier method. Results: A total of 271 patients were included. Statistically significant variables for improved survival on multivariate analysis included age <65 years, lack of extracranial metastases, control of primary tumor, histology (non-small-cell lung carcinoma), and use of stereotactic radiosurgery. The median survival for all patients was 10.2 months. Survival of patients in recursive partitioning analysis (RPA) class 1 was better (21.4 months) than those in RPA class 2 (9.0 months, p < 0.001), RPA class 3 (8.9 months, p = 0.15), or the combined group of RPA classes 2 and 3 (9.0 months, p < 0.001). Patients had a median survival of 10.6 months after documented gross total resection and 8.7 months after subtotal resection, which approached statistical significance (p 0.07). Those who were treated with stereotactic radiosurgery had a median survival of 17.1 months, which was greater than patients who were not treated with stereotactic radiosurgery (8.9 months, p = 0.006). Conclusions: This analysis supports the prognostic significance of the RPA classification in patients with a single brain metastasis who undergo surgical resection and adjuvant therapy. RPA class 1 patients have a very favorable prognosis with a median survival of 21.4 months.

  10. Prognostic significance of KRAS gene mutations in colorectal cancer - preliminary study

    PubMed Central

    Dinu, D; Dobre, M; Panaitescu, E; Bîrlă, R; Iosif, C; Hoara, P; Caragui, A; Boeriu, M; Constantinoiu, S; Ardeleanu, C

    2014-01-01

    Objective: The prognostic significance of KRAS gene mutations, evaluated by using two methods in patients with colorectal cancer (CRC). Material and Methods: Retrospective study involving 58 patients diagnosed with CRC and treated between 2003 and 2010 in the General and Esophageal Surgery Clinic of “Sf. Maria” Hospital, Bucharest. The macroscopic and microscopic examination of the resected specimens was also processed for genetic analysis in NIRDPBS, where KRAS status was determined by using two methods: PCR-RFLP and pyrosequencing. Results: The clinical and biological parameters of the patients were assessed for 72 months in average. A relapse in 21 patients and a 5-year survival rate of 79.3% was discovered. The genetic analyses of KRAS gene found mutations in 22 cases (45.3%): 17 cases had mutations in codon 12, 5 cases in codon 13. The survival rate analyses of patients with wild KRAS gene compared with the patients carrying the mutation on codon 12 /13 revealed a superposition of the survival curve. The statistical analysis based on the TNM stage revealed different survival curves in stage I and II, shorter survival period in patients with KRAS mutation on codon 13 than in those with wild type gene (stage I - p_value=0.015; stage II - p_value=0.000). Conclusions: It was not found that KRAS gene status had any prognostic significance. Nevertheless, for stage I and II patients, the mutation found on codon 13 determined a statistic significant shorter survival rate than for those with wild type. The results obtained by using the pyrosequencing method for the determination of KRAS gene status proved that it represented a reliable and reproducible method. PMID:25713627

  11. Prognostic significance of tPA/PAI-1 complex in patients with heart failure and preserved ejection fraction.

    PubMed

    Winter, Max-Paul; Kleber, Marcus E; Koller, Lorenz; Sulzgruber, Patrick; Scharnagl, Hubert; Delgado, Graciela; Goliasch, Georg; März, Winfried; Niessner, Alexander

    2017-02-28

    Heart failure with preserved ejection fraction (HFpEF) represents a major epidemic, clinical and public health problem with rising patient numbers every year. Traditional markers for heart failure have been shown to be of limited sensitivity in patients with HFpEF, as those do not reflect pathophysiology of the disease properly. Dysregulation of haemostasis is thought to be central for the initiation and progression of HFpEF. For this reason, we aimed to assess markers of fibrinolytic activity as potential biomarkers for risk assessment in patients with HFpEF. We evaluated blood coagulation parameters in 370 patients with HFpEF included in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study. Within an observation period of 9.7 years, 40 percent of these patients died from any cause. tPA/PAI-1 complex significantly predicted all-cause mortality with a hazard ratio (HR) of 1.24 (95 % confidence interval [CI] 1.04-1.47) per increase of 1 SD and cardiovascular mortality with a HR 1.26 (95 % CI 1.02-1.56) per increase of 1 SD. Both associations remained significant after adjustment for cardiovascular risk factors, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and frequent HFpEF- related comorbidities. Importantly, tPA/PAI-1 complex had additional prognostic value above and beyond NT-proBNP as indicated by integrated discrimination improvement (0.0157, p=0.017). In conclusion, the concentration of tPA/PAI-1 complex is an independent predictor of mortality from all causes and from cardiovascular causes in patients with HFpEF. The concomitant measurement of tPA/PAI-1 complex might be useful in clinical practice to add prognostic value to traditional markers of heart failure.

  12. Prognostic Significance of 11q23 Aberrations in Adult Acute Myeloid Leukemia and the Role of Allogeneic Stem Cell Transplantation

    PubMed Central

    Chen, Yiming; Kantarjian, Hagop; Pierce, Sherry; Faderl, Stefan; O’Brien, Susan; Qian, Wei; Abruzzo, Lynn; de Lima, Marcos; Kebriaei, Partow; Jabbour, Elias; Daver, Naval; Kadia, Tapan; Estrov, Zeev; Garcia-Manero, Guillermo; Cortes, Jorge; Ravandi, Farhad

    2014-01-01

    The clinical features and outcomes of 148 patients with acute myeloid leukemia (AML) and 11q23 chromosomal abnormalities were compared with those of 2640 patients with non-11q23 AML. Patients with t(9;11)), t(6;11), or other 11q23 balanced translocations [t(11;v)(q23;v)] presented at a younger age and with higher percentage of bone marrow blasts. Unbalanced 11q23 abnormalities were commonly associated with deletions of chromosomes 5q, 7q and/or complex karyotypes. In multivariate analysis, when compared to patients with non-11q23 AML and unfavorable risk karyotype, there was a significant difference in overall survival (OS) for patients with t(9;11) (P = .004), whereas there were no difference in OS for patients with t(6;11) (P = .62), t(11;19) (P = 0.20), and unbalanced 11q23 aberrations (P = .85) or t(11;v)(q23;v) (P = 0.59), indicating that t(9;11) has an independent intermediate prognostic factor, with all others poor prognostic factors for OS; this was further confirmed by comparing them with patients with non-11q23 AML and intermediate risk karyotype. Using intention-to treat analysis based on donor availability, we also noted that allogeneic stem cell transplant (SCT) in first remission had a significant benefit towards improving OS (P < 0.001) and relapse-free survival (P<0.001) in patients with AML and 11q23 abnormalities. PMID:23135353

  13. MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32.

    PubMed

    Kelly, Andrew D; Haibe-Kains, Benjamin; Janeway, Katherine A; Hill, Katherine E; Howe, Eleanor; Goldsmith, Jeffrey; Kurek, Kyle; Perez-Atayde, Antonio R; Francoeur, Nancy; Fan, Jian-Bing; April, Craig; Schneider, Hal; Gebhardt, Mark C; Culhane, Aedin; Quackenbush, John; Spentzos, Dimitrios

    2013-01-01

    Although microRNAs (miRNAs) are implicated in osteosarcoma biology and chemoresponse, miRNA prognostic models are still needed, particularly because prognosis is imperfectly correlated with chemoresponse. Formalin-fixed, paraffin-embedded tissue is a necessary resource for biomarker studies in this malignancy with limited frozen tissue availability. We performed miRNA and mRNA microarray formalin-fixed, paraffin-embedded assays in 65 osteosarcoma biopsy and 26 paired post-chemotherapy resection specimens and used the only publicly available miRNA dataset, generated independently by another group, to externally validate our strongest findings (n = 29). We used supervised principal components analysis and logistic regression for survival and chemoresponse, and miRNA activity and target gene set analysis to study miRNA regulatory activity. Several miRNA-based models with as few as five miRNAs were prognostic independently of pathologically assessed chemoresponse (median recurrence-free survival: 59 months versus not-yet-reached; adjusted hazards ratio = 2.90; P = 0.036). The independent dataset supported the reproducibility of recurrence and survival findings. The prognostic value of the profile was independent of confounding by known prognostic variables, including chemoresponse, tumor location and metastasis at diagnosis. Model performance improved when chemoresponse was added as a covariate (median recurrence-free survival: 59 months versus not-yet-reached; hazard ratio = 3.91; P = 0.002). Most prognostic miRNAs were located at 14q32 - a locus already linked to osteosarcoma - and their gene targets display deregulation patterns associated with outcome. We also identified miRNA profiles predictive of chemoresponse (75% to 80% accuracy), which did not overlap with prognostic profiles. Formalin-fixed, paraffin-embedded tissue-derived miRNA patterns are a powerful prognostic tool for risk-stratified osteosarcoma management strategies. Combined miRNA and mRNA analysis

  14. MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32

    PubMed Central

    2013-01-01

    Background Although microRNAs (miRNAs) are implicated in osteosarcoma biology and chemoresponse, miRNA prognostic models are still needed, particularly because prognosis is imperfectly correlated with chemoresponse. Formalin-fixed, paraffin-embedded tissue is a necessary resource for biomarker studies in this malignancy with limited frozen tissue availability. Methods We performed miRNA and mRNA microarray formalin-fixed, paraffin-embedded assays in 65 osteosarcoma biopsy and 26 paired post-chemotherapy resection specimens and used the only publicly available miRNA dataset, generated independently by another group, to externally validate our strongest findings (n = 29). We used supervised principal components analysis and logistic regression for survival and chemoresponse, and miRNA activity and target gene set analysis to study miRNA regulatory activity. Results Several miRNA-based models with as few as five miRNAs were prognostic independently of pathologically assessed chemoresponse (median recurrence-free survival: 59 months versus not-yet-reached; adjusted hazards ratio = 2.90; P = 0.036). The independent dataset supported the reproducibility of recurrence and survival findings. The prognostic value of the profile was independent of confounding by known prognostic variables, including chemoresponse, tumor location and metastasis at diagnosis. Model performance improved when chemoresponse was added as a covariate (median recurrence-free survival: 59 months versus not-yet-reached; hazard ratio = 3.91; P = 0.002). Most prognostic miRNAs were located at 14q32 - a locus already linked to osteosarcoma - and their gene targets display deregulation patterns associated with outcome. We also identified miRNA profiles predictive of chemoresponse (75% to 80% accuracy), which did not overlap with prognostic profiles. Conclusions Formalin-fixed, paraffin-embedded tissue-derived miRNA patterns are a powerful prognostic tool for risk-stratified osteosarcoma management

  15. Prognostic significance of mild aortic regurgitation in predicting mortality after transcatheter aortic valve replacement.

    PubMed

    Jones, Brandon M; Tuzcu, E Murat; Krishnaswamy, Amar; Popovic, Zoran; Mick, Stephanie; Roselli, Eric E; Gul, Sajjad; Devgun, Jasneet; Mistry, Sohi; Jaber, Wael A; Svensson, Lars G; Kapadia, Samir R

    2016-09-01

    Moderate to severe aortic regurgitation after transcatheter aortic valve replacement is associated with worse outcomes. The impact of mild aortic regurgitation has been less clear, possibly because of the broad categories that have been used in clinical trials, but holds increasing importance in the study of next-generation devices in low- and intermediate-risk cohorts. A more granular scheme, which is common in clinical practice and proposed for future trials, may add prognostic value. We evaluated all patients undergoing transfemoral transcatheter aortic valve replacement at the Cleveland Clinic from 2006 to 2012. The degree of aortic regurgitation after transcatheter aortic valve replacement was reported from the echocardiography database based on a clinical, transthoracic echocardiogram performed within 30 days of the procedure. Aortic regurgitation was finely discriminated on the basis of a multiwindow, multiparametric, integrative approach using our usual clinical scale: none, trivial to 1+, 1+, 1 to 2+, 2+, 2 to 3+, 3+, 3 to 4+, or 4+. There were 237 patients included in the analysis. By controlling for age, gender, Society of Thoracic Surgeons score, baseline ejection fraction, and aortic regurgitation before transcatheter aortic valve replacement, there was a significant increase in mortality for each half grade of aortic regurgitation compared with the complete absence of aortic regurgitation after transcatheter aortic valve replacement. The unit hazard ratio for each 1+ increase in aortic regurgitation after transcatheter aortic valve replacement was 2.26 (95% confidence interval, 1.48-3.43; P < .001) considering aortic regurgitation as a continuous variable. Other clinical variables did not significantly affect mortality. Even mild aortic regurgitation after transcatheter aortic valve replacement is associated with worse long-term mortality. There may be prognostic value in reporting milder categories of aortic regurgitation with more granular

  16. 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

  17. Prognostic significance of p16 INK4a alteration for Ewing sarcoma: a meta-analysis.

    PubMed

    Honoki, Kanya; Stojanovski, Elizabeth; McEvoy, Mark; Fujii, Hiromasa; Tsujiuchi, Toshifumi; Kido, Akira; Takakura, Yoshinori; Attia, John

    2007-09-15

    Despite findings from individual studies regarding prognostic factors for Ewing sarcoma, no conclusive results have been produced, partly because of small sample sizes. The objective of the current study was to evaluate whether the presence of p16(INK4a) alteration is associated with a poorer prognosis in patients with Ewing sarcomas. A review was conducted of publications that assessed associations between p16(INK4a) status and 2-year survival among patients with Ewing sarcoma. The association between metastatic disease at initial diagnosis and 2-year survival was evaluated by synthesizing data in the form of risk ratios. Of 11 studies that were identified in the initial search strategy, 6 studies, representing 188 patients, met the inclusion criteria and, consequently, were pooled for quantitative analyses. The estimated pooled risk ratio of p16(INK4a) aberration was 2.17 (95% confidence interval [95% CI], 1.55-3.03; P < .001), whereas the estimated pooled risk ratio of metastasis at diagnosis among the 164 eligible patients was 2.60 (95% CI, 1.71-3.97; P < .001). There was no statistically significant difference in the pooled estimated risk ratios of p16(INK4a) aberration for a poor prognosis between patients with and without metastasis at diagnosis (1.86 and 2.21, respectively; P > .59). The presence of p16(INK4a) alteration was a statistically significant predictor of prognosis for patients with Ewing sarcoma. Along with other prognostic factors, such as metastasis, the p16(INK4a) alteration may be a potential candidate for improving the risk-stratifying strategy for patients with these tumors. (c) 2007 American Cancer Society.

  18. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    PubMed Central

    Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

    2014-01-01

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target. PMID:24978437

  19. The Prognostic Significance of c-MET and EGFR Overexpression in Resected Gastric Adenocarcinomas.

    PubMed

    Paliga, Aleksandra; Marginean, Horia; Tessier-Cloutier, Basile; Purgina, Bibianna; Jonker, Derek; Marginean, Esmeralda C

    2015-06-29

    Epidermal growth factor receptor (EGFR) and c-MET are tyrosine kinase growth factor receptors implicated in gastric cancer (GC), and their pathways appear to be interdependent. The aim of this study was to investigate the prognostic value of EGFR and c-MET protein overexpression by immunohistochemistry in Canadian patients with resected GC and correlate it with clinicopathologic characteristics and overall survival (OS). Tissue microarray blocks were constructed from 120 resected GCs stained with EGFR and c-MET and scored semiquantitatively (0 to 3+). Each receptor's expression was compared with clinicopathologic characteristics and survival. Descriptive statistics, Kaplan-Meyer, and Cox regression were used for statistical analyses. Of the 113 interpretable cases, overexpression of EGFR and c-MET was noted in 17 (15%) and 65 (57%), respectively; coexpression of EGFR and c-MET was observed in 12 (10%) of GC. EGFR and c-MET overexpression correlated with poor OS: median 13 versus 30 months in EGFR positive versus negative GC (hazard ratio [HR]=1.67, P=0.11); 27 versus 49 months in c-MET positive versus negative GC (HR=1.17, P=0.49), respectively. GC coexpressing EGFR and c-MET was significantly correlated with poor survival: 12 versus 29 months in double-positive versus rest of tumors both in univariate (HR=2.62, P=0.003) and multivariate analyses (HR=2.58, P=0.01). This study describes the prevalence and prognostic value of EGFR and c-MET in a Canadian population of patients undergoing curative intent resection for GC. Both c-MET and EGFR overexpression trended toward poor OS, but only the group with EGFR+/c-MET+ GC reached statistical significance on multivariate analysis.

  20. Significance of T stadium and grading as prognostic factors in transitional cell carcinoma of the ureter.

    PubMed

    Fiori, Enrico; Cavallaro, Giuseppe; Paparelli, Claudia; Decesare, Alessandro; Bononi, Marco; Galati, Gaspare; Tiziano, Giuseppe; Cavallaro, Antonino; Cangemi, Vincenzo

    2004-01-01

    Surgery is nowadays the standard treatment for carcinoma of the ureter, even if adjuvant therapies can modify the prognosis in selected patients. Because of the small number of patients in the literature series, the significance of prognostic factors that can be used in clinical practice is still controversial, as is the choice of the most suitable surgical and adjuvant treatment. We considered 27 consecutive patients (Ta-T2 N0 M0) who underwent radical surgery (nephroureterectomy with bladder cuff excision and lymphoadenectomy) for transitional cell carcinoma of the ureter, from 1982 through 1992. Seven patients (25.9%) had Ta tumors, 7 patients (25.9%) had T1 tumors and 13 patients (48.2%) had T2 tumors. In 4 cases (14.8%) the tumor was well-differentiated (G1), in 14 cases (51.8%) it was mildly-differentiated (G2), and in 9 cases (33.4%) it was poorly-differentiated. Thirteen of the 14 patients affected by Ta-T1 tumors were alive 10 years after surgery (one patient lost at follow-up); in the T2 tumor group the 5-year survival rate was 84.6% and 10-year survival rate was 69.2%. According to grading, the 10-year survival rate was 100% for G1 tumors, the 3, 5 and 10-year survival rates were, respectively, 100%, 92.8% G3 tumors. Data from our study show the significance of the T stage and grading as prognostic factors.

  1. High expression of CXCR3 is an independent prognostic factor in glioblastoma patients that promotes an invasive phenotype.

    PubMed

    Pu, Yi; Li, Shouwei; Zhang, Chuanbao; Bao, Zhaoshi; Yang, Zhengxiang; Sun, Lihua

    2015-03-01

    Chemokines are a superfamily of small heparin-binding cytokines that induce leukocytes to migrate to sites of inflammation or injury through interacting with specific transmembrane G protein-coupled receptors. Currently, attention is focused on chemokine/chemokine receptor pairs and their ability to promote tumor cell migration and angiogenesis. The chemokine receptor CXCR3 is involved in tumor metastasis and is used as a prognostic biomarker. However, its relationship with the clinicopathological features of primary glioblastoma multiforme (pGBM) and its potential prognostic value have yet to be investigated. Here, we report that high CXCR3 expression conferred poor survival in pGBM patients. Further analysis showed that CXCR3 served as an independent prognostic biomarker for pGBM patients. In addition, functional assays indicated that CXCR3 induced glioma cell invasion. Therefore, this evidence indicates CXCR3 is an independent prognostic factor for pGBM patients and promotes an invasive phenotype, which suggests a new potential biotarget for glioblastoma multiforme therapy.

  2. Neuroendocrine differentiation is an independent prognostic factor in chemotherapy-treated nonsmall cell lung carcinoma.

    PubMed

    Schleusener, J T; Tazelaar, H D; Jung, S H; Cha, S S; Cera, P J; Myers, J L; Creagan, E T; Goldberg, R M; Marschke, R F

    1996-04-01

    Neuroendocrine differentiation can be identified in 10-30% of patients with nonsmall cell lung carcinoma (NSCLC) by immunohistochemical or electron microscopic techniques. However, its clinical significance is not well established. Tumors from 107 patients with Stage IIIA, IIIB, and IV NSCLC treated with cisplatin/etoposide with or without hydrazine in the North Central Cancer Treatment Group and Mayo Clinic protocols were analyzed immunohistochemically with antibodies to chromogranin A (CGA), Leu 7 (CD 57), and synaptophysin (SY). These results were compared with clinical outcomes. Keratin AE1/AE3, used as a control, was positive in 99.1% of cases; 34.6% had positive staining for at least 1 neuroendocrine marker, and 11.3% had positive staining for 2 or more markers. CGA was positive in 4.7%, Leu 7 in 18.7%, and SY in 24.3% of cases. A significant increase in survival was seen in patients with tumors expressing any one neuroendocrine marker or any combination of neuroendocrine markers (P < or = 0.01). There was no correlation between the presence of neuroendocrine differentiation and either response to chemotherapy or time to disease progression (P > 0.3), nor was there any correlation between chemotherapy response, time to progression, or survival with staining intensity or percent of cells positive per case. Neuroendocrine differentiation may be of prognostic significance in patients with advanced stage NSCLC treated with chemotherapy.

  3. Significant prognostic value of circulating tumor cells in esophageal cancer patients: A meta-analysis.

    PubMed

    Wang, Shuyu; Du, Hongyang; Li, Guixia

    2017-02-02

    Esophageal cancer is the sixth leading cause of cancer death worldwide. Detection of circulating tumor cells (CTCs) is emerging as a novel strategy for predicting cancer patient prognosis. Here we performed a comprehensive literature search to identify relevant articles in EMbase, PubMed, EBSCO, OVID, Cochrane Database, CNKI, WanFangdata and VIPdata. Meta-analysis was conducted using Stata12.0 software, according to the inclusion and exclusion criteria, extracted data and assessment methodology. Thirteen eligible literature studies were included with a total of 979 esophageal squamous cell carcinoma patients, including 424 CTC-positive and 684 CTC-negative cases. Meta-analysis showed that the presence of CTCs was associated with both worse progression-free/disease-free survival [hazard ration (HR) = 2.32, 95% confidence interval (CI) = 1.57 - 3.43, p < 0.001] and poorer overall survival [HR = 2.64, 95% CI = 1.69 - 4.14, p < 0.001]. Further subgroup analyses demonstrated that CTC-positive patients also showed worse progression-free/disease-free survival and poorer overall survival in different subsets. In summary, our meta-analysis provides strong evidence that detection of CTCs in the peripheral blood is an independent prognostic indicator of poor outcome for esophageal squamous cell carcinoma patients.

  4. Evaluation and prognostic significance of ACAT1 as a marker of prostate cancer progression.

    PubMed

    Saraon, Punit; Trudel, Dominique; Kron, Ken; Dmitromanolakis, Apostolos; Trachtenberg, John; Bapat, Bharati; van der Kwast, Theodorus; Jarvi, Keith A; Diamandis, Eleftherios P

    2014-04-01

    Prostate cancer is the second leading cause of cancer-related death among men in North America. While a majority of prostate cancer cases remain indolent, subsets of patients develop aggressive cancers, which may lead to death. The current methods of detection include digital rectal examination and the serum PSA test. However, due to lack of specificity, neither of these approaches is able to accurately discriminate between indolent and aggressive cancer, which is why there is a need for additional prognostic factors. Previously, we identified enzymes of the ketogenic pathway, particularly ACAT1, to be elevated in aggressive prostate cancer. In the current study, we assessed the diagnostic and prognostic potential of ACAT1 by analyzing its expression using immunohistochemistry on a tissue microarray consisting of 251 clinically localized prostate cancer patients who have undergone radical prostatectomy. Using quantitative digital imaging software, we found that ACAT1 expression was significantly greater in cancerous cores compared to adjacent benign cores (P < 0.0001), in Gleason score (GS) ≥8 cancers versus GS≤6 cancers (P < 0.0001), GS≥8 cancers versus GS7 cancers (P = 0.001), as well as pT3/pT4 versus pT2 cancers (P = 0.001). In addition, ACAT1 predicted biochemical recurrence in univariate (HR, 1.81, CI = 1.13-2.9, P = 0.0128), and multivariate models (HR, 1.69, CI = 1.01-2.81, P = 0.0431) including pre-operative PSA level, Gleason score and pathological stage. In univariate time-to-recurrence analysis, ACAT1 expression predicted recurrence in ERG negative cases (P = 0.0025), whereas ERG positive cases did not display any differences. Taken together, these findings indicate that ACAT1 expression could serve as a potential prognostic marker in prostate cancer, specifically in differentiating indolent and aggressive forms of cancer. © 2013 Wiley Periodicals, Inc.

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

    PubMed

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

    2016-01-01

    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. 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. 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. 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.

  6. The differential expression of omega-3 and omega-6 fatty acid metabolising enzymes in colorectal cancer and its prognostic significance.

    PubMed

    Alnabulsi, Abdo; Swan, Rebecca; Cash, Beatriz; Alnabulsi, Ayham; Murray, Graeme I

    2017-06-06

    Colorectal cancer is a common malignancy and one of the leading causes of cancer-related deaths. The metabolism of omega fatty acids has been implicated in tumour growth and metastasis. This study has characterised the expression of omega fatty acid metabolising enzymes CYP4A11, CYP4F11, CYP4V2 and CYP4Z1 using monoclonal antibodies we have developed. Immunohistochemistry was performed on a tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosa. The differential expression of CYP4A11 and CYP4F11 showed a strong association with survival in both the whole patient cohort (hazard ratio (HR)=1.203, 95% CI=1.092-1.324, χ(2)=14.968, P=0.001) and in mismatch repair-proficient tumours (HR=1.276, 95% CI=1.095-1.488, χ(2)=9.988, P=0.007). Multivariate analysis revealed that the differential expression of CYP4A11 and CYP4F11 was independently prognostic in both the whole patient cohort (P=0.019) and in mismatch repair proficient tumours (P=0.046). A significant and independent association has been identified between overall survival and the differential expression of CYP4A11 and CYP4F11 in the whole patient cohort and in mismatch repair-proficient tumours.

  7. 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

  8. Prognostic significance of the expression of nuclear eukaryotic translation initiation factor 5A2 in human melanoma.

    PubMed

    Khosravi, Shahram; Martinka, Magdalena; Zhou, Youwen; Ong, Christopher J

    2016-11-01

    Eukaryotic translation initiation factor 5A2 (EIF5A2) expression is upregulated in various cancers. The present authors previously demonstrated that cytoplasmic EIF5A2 expression increases with melanoma progression and inversely correlates with patient survival. Other studies have suggested that nuclear EIF5A2 may also play a role in oncogenesis. The present study used immunohistochemistry and tissue microarray with a large number of melanocytic lesions (n=459) and demonstrated that nuclear EIF5A2 expression was significantly upregulated between common acquired nevi, dysplastic nevi and primary melanomas, and between primary melanomas and metastatic melanomas. Nuclear EIF5A2 expression was inversely associated with overall and disease-specific 5-year survival rate for all (P<0.001) and primary (P=0.014 and P=0.015, respectively) melanoma patients. Nuclear EIF5A2 expression was directly associated with melanoma thickness (P=0.036) and American Joint Committee on Cancer staging (P<0.001), which suggests the possible role of nuclear EIF5A2 in melanoma cell invasion. Subsequently, the present study investigated the association between the expression of nuclear EIF5A2 and matrix metalloproteinase-2 (MMP-2), which is an important factor for promoting cancer cell invasion. Nuclear EIF5A2 and a strong MMP-2 expression were directly associated, and their concurrent expression was significantly associated with a poorer overall and disease-specific 5-year survival rate for all and primary melanoma patients. Nuclear and cytoplasmic EIF5A2 expression were also demonstrated to be significantly associated, and simultaneous expression of the two forms of EIF5A2 was significantly associated with poor overall and disease-specific 5-year survival rates for all and primary melanoma patients. Multivariate Cox regression analysis revealed that nuclear EIF5A2 expression alone and in combination with cytoplasmic EIF5A2 expression was an adverse independent prognostic factor for all and

  9. Prognostic significance of the expression of nuclear eukaryotic translation initiation factor 5A2 in human melanoma

    PubMed Central

    Khosravi, Shahram; Martinka, Magdalena; Zhou, Youwen; Ong, Christopher J.

    2016-01-01

    Eukaryotic translation initiation factor 5A2 (EIF5A2) expression is upregulated in various cancers. The present authors previously demonstrated that cytoplasmic EIF5A2 expression increases with melanoma progression and inversely correlates with patient survival. Other studies have suggested that nuclear EIF5A2 may also play a role in oncogenesis. The present study used immunohistochemistry and tissue microarray with a large number of melanocytic lesions (n=459) and demonstrated that nuclear EIF5A2 expression was significantly upregulated between common acquired nevi, dysplastic nevi and primary melanomas, and between primary melanomas and metastatic melanomas. Nuclear EIF5A2 expression was inversely associated with overall and disease-specific 5-year survival rate for all (P<0.001) and primary (P=0.014 and P=0.015, respectively) melanoma patients. Nuclear EIF5A2 expression was directly associated with melanoma thickness (P=0.036) and American Joint Committee on Cancer staging (P<0.001), which suggests the possible role of nuclear EIF5A2 in melanoma cell invasion. Subsequently, the present study investigated the association between the expression of nuclear EIF5A2 and matrix metalloproteinase-2 (MMP-2), which is an important factor for promoting cancer cell invasion. Nuclear EIF5A2 and a strong MMP-2 expression were directly associated, and their concurrent expression was significantly associated with a poorer overall and disease-specific 5-year survival rate for all and primary melanoma patients. Nuclear and cytoplasmic EIF5A2 expression were also demonstrated to be significantly associated, and simultaneous expression of the two forms of EIF5A2 was significantly associated with poor overall and disease-specific 5-year survival rates for all and primary melanoma patients. Multivariate Cox regression analysis revealed that nuclear EIF5A2 expression alone and in combination with cytoplasmic EIF5A2 expression was an adverse independent prognostic factor for all and

  10. MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma

    PubMed Central

    2013-01-01

    Background Deregulation of microRNA (miRNA) transcript levels has been observed in many types of tumors including osteosarcoma. Molecular pathways regulated by differentially expressed miRNAs may contribute to the heterogeneous tumor behaviors observed in naturally occurring cancers. Thus, tumor-associated miRNA expression may provide informative biomarkers for disease outcome and metastatic potential in osteosarcoma patients. We showed previously that clusters of miRNAs at the 14q32 locus are downregulated in human osteosarcoma. Methods Human and canine osteosarcoma patient’s samples with clinical follow-up data were used in this study. We used bioinformatics and comparative genomics approaches to identify miRNA based prognostic biomarkers in osteosarcoma. Kaplan-Meier survival curves and Whitney Mann U tests were conducted for validating the statistical significance. Results Here we show that an inverse correlation exists between aggressive tumor behavior (increased metastatic potential and accelerated time to death) and the residual expression of 14q32 miRNAs (using miR-382 as a representative of 14q32 miRNAs) in a series of clinically annotated samples from human osteosarcoma patients. We also show a comparable decrease in expression of orthologous 14q32 miRNAs in canine osteosarcoma samples, with conservation of the inverse correlation between aggressive behavior and expression of orthologous miRNA miR-134 and miR-544. Conclusions We conclude that downregulation of 14q32 miRNA expression is an evolutionarily conserved mechanism that contributes to the biological behavior of osteosarcoma, and that quantification of representative transcripts from this family, such as miR-382, miR-134, and miR-544, provide prognostic and predictive markers that can assist in the management of patients with this disease. PMID:23311495

  11. Prognostic significance of HLA EMR8-5 immunohistochemically analyzed expression in osteosarcoma.

    PubMed

    Nada, Ola H; Ahmed, Naglaa S; Abou Gabal, Hoda H

    2014-03-25

    Defects in Human Leukocyte Antigen (HLA) class I antigen expression and/or function in tumor cells have been extensively investigated, because of their potential role in the escape of tumor cells from T cell recognition and destruction. The researchers evaluated HLA class I expression in tumor tissue as a prognostic factor in osteosarcoma patients and as a predictor of their survival. This retrospective cohort study was conducted at the pathology laboratory of Ain Shams University Hospital, and Ain Shams University Specialized Hospital during the period between January 2009 and January 2012. The researchers investigated HLA class I expression in primary osteosarcoma by immunohistochemistry using EMR8-5 mAbs. Furthermore, researchers evaluated the correlation between HLA class I expression and the clinicopathological status and outcome in formalin fixed paraffin embedded tissues from thirty six (36) patients with osteosarcoma. A high expression of HLA class I was detected in 18 (50) % of tumor samples examined; while tumors with low or negative expression represented 9 (25%) cases each. Data indicate that the overall survival rate of patients with tumors highly expressing HLA class I was significantly higher than those with low or negative expression. Down-regulation of class I antigen expression is associated with features of aggressive disease and a poorer prognosis. Therefore, it is imperative to identify HLA as a prognostic factor at the time of diagnosis to detect chemotherapy-resistant tumors and to generate a modified treatment regimen. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1159334857109547.

  12. 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

    2015-12-23

    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.

  13. Clinical and Prognostic Significance of Positive Hepatojugular Reflux on Discharge in Acute Heart Failure: Insights from the ESCAPE Trial

    PubMed Central

    2017-01-01

    Background. There has been a decline in emphasis of the value of physical examination in heart failure (HF) with increased reliance on cardiac imaging. We aim to study the clinical and prognostic significance of positive hepatojugular reflux (HJR) on discharge in patients hospitalized with HF. Methods. Using the ESCAPE trial data, patients were compared according to the presence or absence of a positive HJR on discharge. The primary study endpoints were all-cause mortality and a composite endpoint of death, rehospitalization, and cardiac transplant during the first 6 months after discharge. Results. Among 392 patients (age: 56 years, 74% men), the HJR correlated well with clinical and objective hemodynamic markers of volume overload including right atrial pressure (RAP, P = 0.002), pulmonary capillary wedge pressure (PCWP, P = 0.006), and inferior vena cava size during inspiration (P = 0.005) and expiration (P = 0.003). The RAP had the highest AUC for predicting a positive HJR on admission (AUC: 0.655, P = 0.004) and discharge (AUC: 0.672, P = 0.001). Cox's proportional hazards analysis revealed that a positive HJR on discharge is an independent predictor of 6-month mortality (estimated hazard ratio: 1.689; 95% CI: 1.032–2.764; P = 0.037) after adjusting for age, baseline creatinine, baseline hematocrit, baseline NYHA class, chronic obstructive pulmonary disease, and the presence of tricuspid regurgitation. Conclusion. The HJR should be routinely checked in patients admitted with acute HF throughout hospitalization and especially on discharge as it serves as an important prognostic marker for postdischarge outcomes. PMID:28316980

  14. Clinical and Prognostic Significance of Positive Hepatojugular Reflux on Discharge in Acute Heart Failure: Insights from the ESCAPE Trial.

    PubMed

    Omar, Hesham R; Guglin, Maya

    2017-01-01

    Background. There has been a decline in emphasis of the value of physical examination in heart failure (HF) with increased reliance on cardiac imaging. We aim to study the clinical and prognostic significance of positive hepatojugular reflux (HJR) on discharge in patients hospitalized with HF. Methods. Using the ESCAPE trial data, patients were compared according to the presence or absence of a positive HJR on discharge. The primary study endpoints were all-cause mortality and a composite endpoint of death, rehospitalization, and cardiac transplant during the first 6 months after discharge. Results. Among 392 patients (age: 56 years, 74% men), the HJR correlated well with clinical and objective hemodynamic markers of volume overload including right atrial pressure (RAP, P = 0.002), pulmonary capillary wedge pressure (PCWP, P = 0.006), and inferior vena cava size during inspiration (P = 0.005) and expiration (P = 0.003). The RAP had the highest AUC for predicting a positive HJR on admission (AUC: 0.655, P = 0.004) and discharge (AUC: 0.672, P = 0.001). Cox's proportional hazards analysis revealed that a positive HJR on discharge is an independent predictor of 6-month mortality (estimated hazard ratio: 1.689; 95% CI: 1.032-2.764; P = 0.037) after adjusting for age, baseline creatinine, baseline hematocrit, baseline NYHA class, chronic obstructive pulmonary disease, and the presence of tricuspid regurgitation. Conclusion. The HJR should be routinely checked in patients admitted with acute HF throughout hospitalization and especially on discharge as it serves as an important prognostic marker for postdischarge outcomes.

  15. Histological Subtype Remains a Significant Prognostic Factor for Survival Outcomes in Patients With Appendiceal Mucinous Neoplasm With Peritoneal Dissemination.

    PubMed

    Huang, Yeqian; Alzahrani, Nayef A; Chua, Terence C; Morris, David L

    2017-04-01

    It has been increasingly recognized that appendiceal mucinous neoplasm with peritoneal dissemination is not a homogenous disease. This study aimed to examine the impact of different histological subtypes on survival of a large cohort of patients with appendiceal mucinous neoplasms uniformly treated by cytoreductive surgery and intraperitoneal chemotherapy. This was a retrospective study of prospectively collected data of patients with peritoneal dissemination of appendiceal neoplasm who underwent cytoreductive surgery and intraperitoneal chemotherapy. The study was conducted by 1 surgical team at St. George Hospital. A total of 444 patients formed the cohort of this study. Histological diagnoses were categorized based on Carr criteria to include acellular mucin, disseminated peritoneal adenomucinosis, peritoneal mucinous neoplasms without signet ring cells, and peritoneal mucinous carcinomatosis with signet cells. Patients with low-grade appendiceal mucinous neoplasms with neoplastic epithelium absent tended to have lower CEA, CA19-9, and CA125 levels preoperatively (p = 0.109, 0.008, and 0.034). Factor analysis showed that histological diagnosis was an independent prognostic factor for survival outcomes (HR = 3.13 (95% CI, 2.34-4.39); p < 0.001), adjusted for peritoneal cancer index >20, completeness of cytoreductive score ≥2, use of early postoperative intraperitoneal chemotherapy, transfusion units, CEA >7.0 mg/L, CA19-9 >24.0 U/mL, and CA125 >24 U/mL. This study was limited by its retrospective nature, lack of uniform classifications of appendiceal mucinous neoplasms in early years, and the heterogeneity of this study cohort given the long study period. Histological subtype remains a significant prognostic factor for survival outcomes in patients with appendiceal mucinous neoplasms. It should be taken into account when selecting patients for cytoreductive surgery, tailoring appropriate adjuvant therapies and follow-up surveillance plan.

  16. Prognostic Significance of Spot Urine Na/K for Longitudinal Changes in Blood Pressure and Renal Function: The Nagahama Study.

    PubMed

    Tabara, Yasuharu; Takahashi, Yoshimitsu; Setoh, Kazuya; Kawaguchi, Takahisa; Kosugi, Shinji; Nakayama, Takeo; Matsuda, Fumihiko

    2017-09-01

    Urinary sodium-to-potassium ratio (Na/K) represents a simple measure of sodium load and has been reported to be associated with blood pressure (BP) levels in a cross-sectional setting even with spot measurements. The aim of the present large-scale cohort study is to determine prognostic significance of spot urine Na/K for longitudinal changes in BP levels and renal function. The present study population consisted of 7,063 individuals from the general population. Clinical parameters were measured at baseline and at a follow-up interval of 5 years. Mean systolic BP was slightly increased during the follow-up period (overall, 124 ± 17 to 125 ± 18 mm Hg; nontreated participants, 119 ± 15 to 122 ± 17 mm Hg). Although, the urinary Na/K demonstrated a linear association with BP in a cross-sectional analysis (P < 0.001), analysis of repeated measured BP values identified baseline Na/K * time interaction, i.e., an intraindividual effect, as an inverse determinant (F = 76.9, P < 0.001) independently of hypertension status and fasting conditions possibly due to regression to the mean of temporary high baseline Na/K values at baseline. Spot urine Na/K values were found to be positively associated with renal function in a cross-sectional analysis (P < 0.001). Although baseline Na/K * time interaction showed inverse associated with renal functional decline (F = 85.8, P < 0.001), this inverse association might not represent physiological relationship in likewise fashion with the analysis for BP. Spot urine Na/K may have limited utility as a prognostic marker of longitudinal BP change, as well as renal functional decline.

  17. Elevated troponin I and its prognostic significance in acute liver failure

    PubMed Central

    2012-01-01

    Introduction Acute liver failure (ALF) is a life-threatening multisystem illness complicated by multiple organ failure (MOF) and haemodynamic disturbances. Morbidity and mortality remains high and various prognostic and scoring models are in use to predict outcome. A recent observation in a large cohort of ALF patients suggested a prognostic value of troponin I (cTnI) and its role as a marker of subclinical myocardial injury and outcome. Methods Data from consecutive ALF patients over a four-year period from January 2007 to March 2011 were included. The aim of this study was to correlate any relationship that may exist between cTnI, mortality, severity of illness and non-hepatic organ failure. Results A total of 218 subjects (age 36 (16 to 90) years, M:F 103:115) were studied, of which 136 had an elevated cTnI > 0.05 μg/L. Higher organ failure scores were found with positive cTnI: APACHE II (19.5 (3 to 51) vs 14 (2 to 51), P = 0.001), APACHE III (81 (15 to 148) vs 59 (8 to 172), P = < 0.001) SOFA (15 (4 to 20) vs 13 (2 to 21), P = 0.027) and SAPS (48 (12 to 96) vs 34 (12 to 97), P = 0.001). Patients with positive cTnI had higher serum creatinine (192 μmol/l (38 to 550) vs 117 μmol/l (46 to 929), P < 0.001), arterial lactate (0.25, P < 0.001) and a lower pH (-0.21, P = 0.002). Also a higher proportion required renal replacement therapy (78% vs 60%, P = 0.006). Patients with elevated cTnI more frequently required vasopressors-norepinephrine (73% vs 50%, P = 0.008). Elevated cTnI did not predict outcome as effectively as other models (AUROC 0.61 (95% CI 0.52 to 0.68)). Conclusions More than 60% of ALF patients in this study demonstrated elevated cTnI. Despite a close correlation with organ failure severity, cTnI was a poor independent predictor of outcome. cTnI may not represent true myocardial injury and may be better viewed as a marker of metabolic stress. PMID:23190744

  18. 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

  19. CUL4A overexpression as an independent adverse prognosticator in intrahepatic cholangiocarcinoma.

    PubMed

    Huang, Gong -Kai; Liu, Ting-Ting; Weng, Shao-Wen; You, Huey-Ling; Wei, Yu-Ching; Chen, Chang-Han; Eng, Hock-Liew; Huang, Wan-Ting

    2017-06-02

    CUL4A has been known for its oncogenic properties in various human cancers. However, its role in intrahepatic cholangiocarcinoma (iCCA) has not been explored. We retrospectively investigated 105 iCCA cases from a single medical institution. Tissue microarrays were used for immunohistochemical analysis of CUL4A expression. CUL4A expression vectors were introduced in cell lines. Cell migration and invasion assays were used to compare the mobility potential of iCCA cells under basal conditions and after manipulation. Then we evaluated the effects of CUL4A on the cell growth by proliferation assay, and further checked the susceptibility to cisplatin in iCCA cells with or without CUL4A overexpression. CUL4A overexpression was detected in 34 cases (32.4%). Patients with CUL4A-overexpressing tumors exhibited shortened disease-free survival (mean, 27.7 versus 90.4 months; P = 0.011). In the multivariate analysis model, CUL4A overexpression was shown to be an independent unfavorable predictor for disease-free survival (P = 0.045). Moreover, stably transfected CUL4A-overexpressing iCCA cell lines displayed an increased mobility potential and enhanced cell growth without impact on susceptibility to cisplatin. Our data demonstrate that overexpression of CUL4A plays an oncogenic role in iCCA and adversely affects disease-free survival. Thus, it may prove to be a powerful prognostic factor and a potential therapeutic target.

  20. PDL1 expression is an independent prognostic factor in localized GIST.

    PubMed

    Bertucci, François; Finetti, Pascal; Mamessier, Emilie; Pantaleo, Maria Abbondanza; Astolfi, Annalisa; Ostrowski, Jerzy; Birnbaum, Daniel

    2015-05-01

    Gastrointestinal stromal tumors (GIST) are the most frequently occurring digestive sarcomas. The prognosis of localized GIST is heterogeneous, notably for patients with an Armed Forces Institute of Pathology (AFIP) intermediate or high risk of relapse. Despite imatinib effectiveness, it is crucial to develop therapies able to overcome the resistance mechanisms. The immune system represents an attractive prognostic and therapeutic target. The Programmed cell Death 1 (PD1)/programmed cell death ligand 1 (PDL1) pathway is a key inhibitor of the immune response; recently, anti-PD1 and anti-PDL1 drugs showed very promising results in patients with solid tumors. However, PDL1 expression has never been studied in GIST. Our objective was to analyze PDL1 expression in a large series of clinical samples. We analyzed mRNA expression data of 139 operated imatinib-untreated localized GIST profiled using DNA microarrays and searched for correlations with histoclinical features including postoperative metastatic relapse. PDL1 expression was heterogeneous across tumors and was higher in AFIP low-risk than in high-risk samples, and in samples without than with metastatic relapse. PDL1 expression was associated with immunity-related parameters such as T-cell-specific and CD8(+) T-cell-specific gene expression signatures and probabilities of activation of interferon α (IFNα), IFNγ, and tumor necrosis factor α (TNFα) pathways, suggesting positive correlation with a cytotoxic T-cell response. In multivariate analysis, the PDL1-low group was associated with a higher metastatic risk independently of the AFIP classification and the KIT mutational status. In conclusion, PDL1 expression refines the prediction of metastatic relapse in localized GIST and might improve our ability to better tailor adjuvant imatinib. In the metastatic setting, PDL1 expression might guide the use of PDL1 inhibitors, alone or associated with tyrosine kinase inhibitors.

  1. PDL1 expression is an independent prognostic factor in localized GIST

    PubMed Central

    Bertucci, François; Finetti, Pascal; Mamessier, Emilie; Pantaleo, Maria Abbondanza; Astolfi, Annalisa; Ostrowski, Jerzy; Birnbaum, Daniel

    2015-01-01

    Gastrointestinal stromal tumors (GIST) are the most frequently occurring digestive sarcomas. The prognosis of localized GIST is heterogeneous, notably for patients with an Armed Forces Institute of Pathology (AFIP) intermediate or high risk of relapse. Despite imatinib effectiveness, it is crucial to develop therapies able to overcome the resistance mechanisms. The immune system represents an attractive prognostic and therapeutic target. The Programmed cell Death 1 (PD1)/programmed cell death ligand 1 (PDL1) pathway is a key inhibitor of the immune response; recently, anti-PD1 and anti-PDL1 drugs showed very promising results in patients with solid tumors. However, PDL1 expression has never been studied in GIST. Our objective was to analyze PDL1 expression in a large series of clinical samples. We analyzed mRNA expression data of 139 operated imatinib-untreated localized GIST profiled using DNA microarrays and searched for correlations with histoclinical features including postoperative metastatic relapse. PDL1 expression was heterogeneous across tumors and was higher in AFIP low-risk than in high-risk samples, and in samples without than with metastatic relapse. PDL1 expression was associated with immunity-related parameters such as T–cell-specific and CD8+ T–cell-specific gene expression signatures and probabilities of activation of interferon α (IFNα), IFNγ, and tumor necrosis factor α (TNFα) pathways, suggesting positive correlation with a cytotoxic T-cell response. In multivariate analysis, the PDL1-low group was associated with a higher metastatic risk independently of the AFIP classification and the KIT mutational status. In conclusion, PDL1 expression refines the prediction of metastatic relapse in localized GIST and might improve our ability to better tailor adjuvant imatinib. In the metastatic setting, PDL1 expression might guide the use of PDL1 inhibitors, alone or associated with tyrosine kinase inhibitors. PMID:26155391

  2. Profiling of Oncogenic Driver Events in Lung Adenocarcinoma Revealed MET Mutation as Independent Prognostic Factor.

    PubMed

    Yeung, Sai F; Tong, Joanna H M; Law, Peggy P W; Chung, Lau Y; Lung, Raymond W M; Tong, Carol Y K; Chow, Chit; Chan, Anthony W H; Wan, Innes Y P; Mok, Tony S K; To, Ka F

    2015-09-01

    Oncogenic driver mutations activating receptor tyrosine kinase pathways are promising predictive markers for targeted treatment. We investigated the mutation profile of an updated driver events list on receptor tyrosine kinase/RAS/PI3K axis and the clinicopathologic implications in a cohort of never-smoker predominated Chinese lung adenocarcinoma. We tested 154 lung adenocarcinomas and adenosquamous carcinomas for EGFR, KRAS, HER2, BRAF, PIK3CA, MET, NRAS, MAP2K1, and RIT1 mutations by polymerase chain reaction-direct sequencing. MET amplification and ALK and ROS1 translocations were assessed by fluorescent in situ hybridizations. MET and thyroid transcription factor-1 protein expressions were investigated by immunohistochemistry. Seventy percent of lung adenocarcinomas carried actionable driver events. Alterations on EGFR (43%), KRAS (11.4%), ALK (6%), and MET (5.4%) were frequently found. ROS1 translocation and mutations involving BRAF, HER2, NRAS, and PIK3CA were also detected. No mutation was observed in RIT1 and MAP2K1. Patients with EGFR mutations had a favorable prognosis, whereas those with MET mutations had poorer overall survival. Multivariate analysis further demonstrated that MET mutation was an independent prognostic factor. Although MET protein expression was detected in 65% of lung adenocarcinoma, only 10% of the MET-immunohistochemistry positive tumors harbor MET DNA alterations that drove protein overexpression. Appropriate predictive biomarker is essential for selecting patients who might benefit from specific targeted therapy. Actionable driver events can be detected in two thirds of lung adenocarcinoma. MET DNA alterations define a subset of patients with aggressive diseases that might potentially benefit from anti-MET targeted therapy. High negative predictive values of thyroid transcription factor-1 and MET expression suggest potential roles as surrogate markers for EGFR and/or MET mutations.

  3. Prognostic significance of myocardial energy expenditure and myocardial efficiency in patients with heart failure with reduced ejection fraction.

    PubMed

    Cetin, Mehmet S; Ozcan Cetin, Elif H; Canpolat, Ugur; Sasmaz, Hatice; Temizhan, Ahmet; Aydogdu, Sinan

    2017-08-14

    In heart failure with reduced ejection fraction (HFrEF) patients, myocardial blood flow (MBF), myocardial energy expenditure (MEE), myocardial efficiency has been poorly evaluated because of the necessity of invasive procedures in the determination of these parameters. Transthoracic echocardiography (TTE) can provide reliable data for MEE, MBF (via coronary sinus (CS) flows). Also, myocardial efficiency can be evaluated by the MEE to MBF ratio. We aim to assess MBF, MEE and energy efficiency and the prognostic value of these parameters in HFrEF. In this prospective study, a total of 80 patients with HFrEF due to either ischemic or non-ischemic etiology and 20 healthy control subjects were included. Median follow-up duration was 901 (27-1004) days. MBF was calculated via coronary sinus blood flow. MEE was measured from circumferential end-systolic stress, stroke volume and left ventricular ejection time. MEE to MBF ratio was determined as MEf. Primary composite end-point (CEP) was cardiovascular mortality, heart transplantation or mechanical circulatory support. MEE and MEf were lower and MBF per minute was higher in HF group compared to control subjects whereas MBF per 100 g left ventricular mass was not different. MEE and MEf have significantly negative correlation with troponin I, BNP, uric acid and positive correlation with epicardial fat thickness. In Cox regression analysis, per one calorie decrease of MEE was associated 4.3 times increased risk [HR 4.396 (95% CI 1.230-15.716)] and per one percent decrease of MEf was associated 3.3 times increased risk of CEP [HR 3.343 (95% CI 1.025-10.905)]. Our study demonstrated that while MEE and MEf diminished in HFrEF, MBF preserved with the symptomatic progression of HF. MEE and MEf were found to be associated with important prognostic markers and independent predictors of CEP in HFrEF. Evaluation of MEE, MBF and MEf with echocardiography may provide an additional data regarding prognostic assessment of HFr

  4. Prognostic significance of ligands belonging to tumour necrosis factor superfamily in acute lymphoblastic leukaemia.

    PubMed

    Bolkun, L; Lemancewicz, D; Jablonska, E; Szumowska, A; Bolkun-Skornicka, U; Moniuszko, M; Dzieciol, J; Kloczko, J

    2015-03-01

    Altered activities of ligands belonging to tumour necrosis factor (TNF) superfamily, namely B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL) and apoptosis inducing ligand (TRAIL) were demonstrated in several haematological diseases including acute lymphoblastic leukaemia (ALL). BAFF, APRIL and TRAIL provide crucial survival signals to immature, naive and activated B cells. These ligands are capable of activating a broad spectrum of intracellular signalling cascades that can either induce apoptosis or protect from programmed cell death. BAFF and APRIL, which can directly activate the NF-κB pathway, have been identified as crucial survival factors for ALL cells. Here, we have analyzed serum BAFF, APRIL and TRAIL concentrations in 48 patients with newly diagnosed ALL and 44 healthy volunteers. The levels of APRIL and BAFF were significantly higher in ALL patients as compared to healthy volunteers. In contrast, concentrations of TRAIL were significantly lower in ALL patients. Moreover, following induction, the levels of APRIL, but not BAFF or TRAIL, were significantly lower in a group of patients with complete remission (CR) as compared to non-respondent (NR) ALL patients. Furthermore, we demonstrated statistically significant differences in concentrations of APRIL between CR MRD-negative and CR, MRD-positive ALL patients. Notably detection of higher concentrations of APRIL was associated with shorter leukaemia-free survival and overall survival. Altogether, our data indicate that APRIL can play an important role in the pathogenesis of ALL and the measurement of APRIL levels can improve prognostication in ALL patients.

  5. Prognostic Significance of Neutrophil to Lymphocyte Ratio, Lymphocyte to Monocyte Ratio, and Platelet to Lymphocyte Ratio in Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Lu, Aiying; Li, Haifeng; Zheng, Yuming; Tang, Minzhong; Li, Jun; Wu, Huihui; Zhong, Weiming; Gao, Jianquan; Ou, Ningjiang

    2017-01-01

    The peripheral blood neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) have been reported to correlate with the prognosis of many malignancies. This study evaluated the prognostic value of pretreatment NLR, LMR, and PLR in nasopharyngeal carcinoma (NPC). A retrospective analysis of clinical and pathological data of 140 NPC patients without distant metastasis during initial treatment was conducted to identify correlations between NLR, LMR, and PLR and clinicopathological features, overall survival, and progression-free survival. Cox proportional hazard regression analysis was used to reveal the independent factors affecting the prognosis of NPC patients. NLR was associated with T staging, N staging, and overall clinical stage grouping of the NPC patients (P < 0.05). NLR ≥ 2.28, LMR < 2.26, and PLR ≥ 174 were significantly associated with a relatively short overall survival (P < 0.05). In addition, NLR ≥ 2.28 was significantly associated with a relatively short progression-free survival (P < 0.05). Cox proportional hazard regression analysis showed that NLR was an independent prognostic factor in NPC. Pretreatment NLR, LMR, and PLR might be a useful complement to TNM staging in the prognostic assessment of NPC patients. PMID:28321405

  6. Prognostic significance of miR-1268a expression and its beneficial effects for post-operative adjuvant transarterial chemoembolization in hepatocellular carcinoma

    PubMed Central

    Lu, Yun-Long; Yao, Jin-Guang; Huang, Xiao-Ying; Wang, Chao; Wu, Xue-Min; Xia, Qiang; Long, Xi-Dai

    2016-01-01

    Our recent investigation has shown that the variables of microRNA-1268a may involve in hepatocellular carcinoma (HCC) tumorigenesis. Here, we attempted to identify the prognostic significance of microRNA-1268a expression in tumor tissues by a retrospective analysis in 411 patients with HCC, and analyze its effects on post-operative adjuvant transarterial chemoembolization (TACE) improving HCC prognosis. All cases received tumor resection or tumor resection plus post-operative adjuvant TACE as an initial treatment. Logistical regression analysis exhibited that microRNA-1268a expression was significantly correlated with tumor stage, tumor grade, tumor size, and microvessel density. Cox regression analysis showed that microRNA-1268a expression was an independent prognostic factor for HCC, and TACE treatment had no effects on prognosis of HCC patients with high microRNA-1268a expression. More intriguingly, TACE improved the prognosis of HCC patients with low microRNA-1268a expression. Functionally, overexpression of microRNA-1268a inhibited while its inhibitor enhanced doxorubicin-induced the death of cancer cells. These results suggest that microRNA-1268a may be an independent prognostic factor for HCC patients, and that decreasing microRNA-1268a expression may be beneficial for post-operative adjuvant TACE treatment in HCC. PMID:27796321

  7. Prognostic significance of fibroblast growth factor receptor 4 polymorphisms on biochemical recurrence after radical prostatectomy in a Chinese population

    PubMed Central

    Chen, Luyao; Lei, Zhengwei; Ma, Xin; Huang, Qingbo; Zhang, Xu; Zhang, Yong; Hao, Peng; Yang, Minggang; Zhao, Xuetao; Chen, Jun; Liu, Gongxue; Zheng, Tao

    2016-01-01

    Fibroblast growth factor receptor 4 (FGFR4) is a transmembrane receptor with ligand-induced tyrosine kinase activity and is involved in various biological and pathological processes. Several polymorphisms of FGFR4 are associated with the incidence and mortality of numerous cancers, including prostate cancer. In this study, we investigated whether the polymorphisms of FGFR4 influence the biochemical recurrence of prostate cancer in Chinese men after radical prostatectomy. Three common polymorphisms (rs1966265, rs2011077, and rs351855) of FGFR4 were genotyped from 346 patients with prostate cancer by using the Sequenom MassARRAY system. Kaplan–Meier curves and Cox proportional hazard models were used for survival analysis. Results showed biochemical recurrence (BCR) free survival was significantly affected by the genotypes of rs351855 but not influenced by rs1966265 and rs2011077. After adjusting for other variables in multivariable analysis, patients with rs351855 AA/AG genotypes showed significantly worse BCR-free survival than those with the GG genotype (HR = 1.873; 95% CI, 1.209–2.901; P = 0.005). Hence, FGFR4 rs351855 could be a novel independent prognostic factor of BCR after radical prostatectomy in the Chinese population. This functional polymorphism may also provide a basis for surveillance programs. Additional large-scale studies must be performed to validate the significance of this polymorphism in prostate cancer. PMID:27640814

  8. Pathological and prognostic significance of matrix metalloproteinase-2 expression in ovarian cancer: a meta-analysis.

    PubMed

    Liu, Chao

    2016-08-01

    Matrix metalloproteinase-2 (MMP-2) has been linked with tumor invasion and metastasis. However, the role of MMP-2 expression in ovarian cancer remains controversial. By searching the PubMed, Embase, Wanfang, and China National Knowledge Infrastructure databases, we conducted a meta-analysis to evaluate the pathological and prognostic significance of MMP-2 in ovarian cancer. Studies were pooled, and the odds ratio (OR) and its corresponding 95 % confidence interval (CI) were calculated. Version 11.0 STATA software was used for statistical analysis. Twenty-seven relevant articles were included for this meta-analysis study. The expression of MMP-2 in cancer tissue was significantly higher than that in benign or normal ovarian tissue [cancer vs. benign, OR 10.09 (95 % CI 6.95-14.64); P < 0.001; cancer vs. normal, OR 30.48 (95 % CI 17.19-54.05); P < 0.001; benign vs. normal, OR 1.88 (95 % CI 1.08-3.29); P = 0.025]. The expression of MMP-2 in stage III-IV or lymph node metastasis was significantly higher than that in stage I-II or that without metastasis, respectively [OR 5.83 (95 % CI 4.32-7.85); P < 0.001; OR 7.20 (95 % CI 4.75-10.91); P < 0.001]. MMP-2 was associated with histological types and grade of ovarian cancer [serous vs. mucinous, OR 1.67 (95 % CI 1.17-2.39); P = 0.004; grade 3 vs. 1, 2, OR 3.23 (95 % CI 2.29-4.55); P < 0.001]. However, the age of patients was not associated with MMP-2 expression [OR 1.25 (95 % CI 0.61-2.58); P = 0.546]. In conclusion, MMP-2 is related to the malignant degree, FIGO stage, histological types and grade, and lymph node metastasis of ovarian cancer. It may play a significant role in clinical guidelines for the treatment and prognostic evaluation.

  9. Prognostic significance of specific magnetic resonance imaging features in canine nasal tumours treated by radiotherapy.

    PubMed

    Agthe, P; Caine, A R; Gear, R N A; Dobson, J M; Richardson, K J; Herrtage, M E

    2009-12-01

    To investigate the prognostic significance of the magnetic resonance (MR) findings of meningeal hyperintensity of the olfactory bulbs and tumour extension into the caudal nasal recess (CNR) in dogs with nasal tumours treated by radiotherapy. MR images of 41 dogs with nasal tumours treated with radiotherapy were reviewed. The occurrence of neurological signs and survival of patients with and without meningeal hyperintensity of the olfactory bulbs and tumour extension into the CNR were analysed together with possible confounding factors including intracranial extension and patient age. There was no significant association between the presence of meningeal hyperintensity or CNR involvement and the occurrence of neurological signs. Although there was a tendency towards shorter survival in dogs with tumour extension into the CNR, multivariable analysis showed no significant difference in survival between dogs with/without CNR involvement, meningeal hyperintensity or intracranial tumour extension (P=0.12, 0.50 and 0.57, respectively). In dogs with nasal tumours treated with radiotherapy, tumour extension into the cranium is not necessarily associated with shorter survival in patients without neurological signs at time of diagnosis. Although a definite influence of CNR involvement on case outcome could not be demonstrated, studies with a larger population are warranted.

  10. 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.

  11. 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

  12. Prognostic significance of p16 and its relationship with human papillomavirus in pharyngeal squamous cell carcinomas.

    PubMed

    Wilson, David D; Crandley, Edwin F; Sim, Austin; Stelow, Edward B; Majithia, Neil; Shonka, David C; Jameson, Mark J; Levine, Paul A; Read, Paul W

    2014-07-01

    The prognostic significance of p16 in squamous cell carcinoma (SCC) of the hypopharynx (HP) and nasopharynx (NP) and relationship between human papillomavirus (HPV) and p16 is unclear. To evaluate the prognostic significance of p16 in pharyngeal subsites (oropharynx [OP], HP, and NP) and assess the relationship between HPV and p16 in the HP and NP. Retrospective medical record review of 172 patients with SCC of the pharynx treated with definitive radiation therapy from 2002 to 2013 at a university tertiary referral center, with tissue available for immunohistochemical analysis. The median follow-up was 30.1 months. A total of 118 patients were treated with chemoradiation, and 54 patients were treated with radiation alone. Immunohistochemical analysis for p16 was performed for all tumors. Hypopharynx and NP tumors were tested for HPV using in situ hybridization, and NP tumors were tested for Epstein-Barr virus. Overall survival, locoregional control, and disease-free survival were analyzed according to p16, HPV, and Epstein-Barr virus status. Thirty-two patients had HP SCC, 127 had OP SCC, and 13 had NP SCC. p16 Was positive in the HP (34%), OP (66%), and NP (46%). Prevalence of HPV was 14% in the HP and 50% in the NP. As a test for HPV, p16 had a positive predictive value of 38% (HP) and 67% (NP) and a negative predictive value of 100% in HP and NP tumors. p16 Status was a significant predictor of all clinical outcomes for patients with OP SCC (P<.001), but not for patients with HP or NP SCC. Patients with Epstein-Barr virus- or HPV-associated NP SCC had improved clinical outcomes. p16 Was not associated with improved outcomes in patients with HP or NP SCC. The positive predictive value of p16 as a test for HPV is too low for p16 testing alone in the HP and NP. However, p16 negativity is sufficient to rule out HPV. As a research approach, we recommend p16 immunohistochemistry as a screening test for HPV in NP SCC and HP SCC followed by confirmatory HPV in situ

  13. Prognostic Significance of the Metabolic Marker Hexokinase-2 in Various Solid Tumors: A Meta-Analysis

    PubMed Central

    Liu, Yulin; Wu, Ke; Shi, Liang; Xiang, Fan; Tao, Kaixiong; Wang, Guobin

    2016-01-01

    Objective Recently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor. Methods Eligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively. Subgroup analysis was also performed according to patients’ ethnicities, tumor types, detection methods, and analysis types. Results Data from 21 included studies with 2532 patients were summarized. HK2 overexpression was significantly associated with worse OS (pooled HR = 1.90, 95% CI = 1.51–2.38, p < 0.001) and PFS (pooled HR = 2.91, 95% CI = 2.02–4.22, p < 0.001) in solid tumor. As to a specific form of cancer, the negative effect of HK2 on OS was observed in hepatocellular carcinoma (pooled HR = 2.06, 95% CI = 1.67–2.54, p < 0.001), gastric cancer (pooled HR = 1.72, 95% CI = 1.09–2.71, p = 0.020), colorectal cancer (pooled HR = 2.89, 95% CI = 1.62–5.16, p < 0.001), but not in pancreatic cancer (pooled HR = 1.13, 95% CI = 0.28–4.66, p = 0.864). No publication bias was found in the included studies for OS (Begg’s test, p = 0.325; Egger’s test, p = 0.441). Conclusion In this meta-analysis, we identified that elevated HK2 expression was significantly associated with shorter OS and PFS in patients with solid tumor, but the association varies according to cancer type. PMID:27824926

  14. Claudin-2 is an independent negative prognostic factor in breast cancer and specifically predicts early liver recurrences.

    PubMed

    Kimbung, Siker; Kovács, Anikó; Bendahl, Pär-Ola; Malmström, Per; Fernö, Mårten; Hatschek, Thomas; Hedenfalk, Ingrid

    2014-02-01

    Predicting any future metastatic site of early-stage breast cancer is important as it significantly influences the prognosis of advanced disease. This study aimed at investigating the potential of claudin-2, over-expressed in breast cancer liver metastases, as a biomarker for predicting liver metastatic propensity in primary breast cancer. Claudin-2 expression was analyzed in two independent cohorts. Cohort 1 included 304 women with metastatic breast cancer diagnosed between 2002 and 2007, while cohort 2 included 237 premenopausal women with early-stage node-negative breast cancer diagnosed between 1991 and 1994. Global transcriptional profiling of fine-needle aspirates from metastases was performed, followed by immunohistochemical analyses in archival primary tumor tissue. Associations between claudin-2 expression and relapse site were assessed by univariable and multivariable Cox regression models including conventional prognostic factors. Two-sided statistical tests were used. CLDN2 was significantly up-regulated (P < 0.001) in liver metastases compared to other metastatic sites. Claudin-2 protein was more frequently expressed in primary tumors from patients who subsequently developed liver metastases (P = 0.02) and high expression was associated with a shorter metastasis-free interval (cohort 1, HR = 1.4, 95% CI = 1.0-1.9; cohort 2, HR = 2.2, 95% CI = 1.3-3.5). Specifically, a significantly shorter interval between primary tumor diagnosis and liver-specific recurrence was observed among patients with high levels of claudin-2 expression in the primary tumor (cohort 1, HR = 2.3, 95% CI = 1.3-3.9). These results suggest a novel role for claudin-2 as a prognostic biomarker with the ability to predict not only the likelihood of a breast cancer recurrence, but more interestingly, the liver metastatic potential of the primary tumor. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. Loss of RUNX3 expression is an independent adverse prognostic factor in diffuse large B-cell lymphoma.

    PubMed

    Duncan, Virginia E; Ping, Zheng; Varambally, Sooryanarayana; Peker, Deniz

    2017-01-01

    Runt-related transcription factor-3 (RUNX3) is an apoptotic factor correlated with tumorigenesis and cancer progression. Enhancer of zeste homolog-2 (EZH2), a histone methyltransferase, has been shown to mediate silencing of RUNX3. We investigated RUNX3 and EZH2 expression in diffuse large B-cell lymphoma (DLBCL). A chart review was conducted and tissue-microarray (TMA) was constructed using archived tissue from 83 DLBCL cases. RUNX3 and EZH2 protein expression was correlated with immunophenotypic subtypes and survival. Loss of RUNX3 was observed in 20 cases; EZH2 expression was observed in 59 cases. RUNX3-negative tumors had significantly lower overall and recurrence-free survival (log-rank test, p < 0.0001 for each). No correlation was found between RUNX3 and EZH2 staining (r = 0.14; p = 0.2). Results suggest a role for the RUNX3 gene in the pathogenesis of DLBCL. Loss of RUNX3 expression strongly correlated with adverse prognosis, independent of subtype. Further studies are warranted to elucidate the biology and prognostic utility of RUNX3 in DLBCL.

  16. α(1,6)Fucosyltransferase expression is an independent prognostic factor for disease-free survival in colorectal carcinoma.

    PubMed

    Muinelo-Romay, L; Villar-Portela, S; Cuevas Alvarez, E; Gil-Martín, E; Fernández-Briera, Almudena

    2011-11-01

    We previously reported that α(1,6)fucosyltransferase (Enzyme class 2.4.1.68) activity and expression are increased in colorectal cancer, suggesting a role for this enzyme in tumor development and progression. However, the possible impact of α(1,6)fucosyltransferase activity or expression on clinical outcomes in colorectal cancer patients has never been studied. Thus, the present study was conducted to determine the value of α(1,6)fucosyltransferase as a prognostic factor for colorectal cancer. α(1,6)Fucosyltransferase expression was analyzed using immunohistochemistry in 141 colorectal tumors, and α(1,6)fucosyltransferase activity was determined in 39 tumors. A complete standardized follow-up of patients was documented until the end of the observation period of 5 years or patient death. Univariate analysis demonstrated the absence of a correlation between enzyme activity and disease evolution. However, in patients with moderate or strong α(1,6)fucosyltransferase expression, a significant decrease in the overall (P = .04) and disease-free (P = .03) survival rates was observed. In addition, when local and distant disease recurrence were considered separately, enzyme expression was found to correlate with local tumor recurrences (P = .01). Furthermore, multivariate analysis showed that α(1,6)fucosyltransferase expression has independent value for predicting tumor recurrences and, specifically, local recurrences. These findings suggest that α(1,6)fucosyltransferase expression may be a good indicator of poor prognosis in colorectal cancer and, therefore, a helpful tool to choose the most effective treatment.

  17. Does clear cell carcinoma of stomach exist? Clinicopathological and prognostic significance of clear cell changes in gastric adenocarcinomas.

    PubMed

    Kim, Joo-Yeon; Park, Do Youn; Kim, Gwang Ha; Jeon, Tae-Yong; Lauwers, Gregory Y

    2014-07-01

    In contrast to clear cell carcinomas developing in other organs (e.g. ovary and uterus), gastric adenocarcinomas with clear cell features are not well characterized. We evaluated a series of 762 gastric adenocarcinomas for the presence of clear cell changes; and investigated the nature of the changes using several histochemical and immunohistochemical markers, their association with various clinicopathological features, and their prognostic significance. Clear cell changes were observed in 8.5% (n = 65) of gastric cancers. Cases with clear cell changes (GCC) were associated significantly with older age, intestinal type histology, body/fundic location, greater depth of invasion, lymph node metastases and lymphovascular invasion. An increasing proportion of clear cell changes indicated a worsening prognosis, and was identified as an independent marker of poor prognosis using the Cox proportional hazard model (hazard ratio, 0.462; P = 0.003). Of 62 GCCs subjected to special staining, 35 cases (55.6%) displayed cytoplasmic accumulation of glycogen, while 21 (33.3%) contained mucin. GCCs showing glycogen accumulation expressed AFP, glypican-3 and CD10 more commonly than those with mucin, which commonly expressed Muc5AC and Muc6. Clear cell gastric adenocarcinoma is a unique subgroup of gastric cancer which, although heterogeneous, has a poor prognosis. © 2014 John Wiley & Sons Ltd.

  18. 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.

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

    PubMed

    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 (I(2)<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.

  20. Prognostic Significance of a Minute Amount of Ascites During Chemoradiotherapy for Locally Advanced Pancreatic Cancer.

    PubMed

    Shinoto, Makoto; Nakamura, Katsumasa; Shioyama, Yoshiyuki; Sasaki, Tomonari; Nishie, Akihiro; Asayama, Yoshiki; Ohga, Saiji; Yoshitake, Tadamasa; Terashima, Kotaro; Asai, Kaori; Matsumoto, Keiji; Honda, Hiroshi

    2016-04-01

    The aim of this study was to investigate the clinical factors for predicting overall survival (OS) and the significance of a minute amount of ascites on computed tomography (CT) in patients with locally advanced pancreatic cancer (LAPC) treated with chemoradiotherapy (CRT). Between 2003 and 2011, 48 consecutive patients with LAPC were treated with CRT. Various clinical factors, including ascites, were evaluated for correlation with OS. A subset analysis of 16 patients with a minute amount of ascites was also performed. The median survival duration and the 1-year OS rates were 11.5 months and 50%, respectively. A minute amount of ascites on CT and elevated carbohydrate antigen 19-9 (CA19-9) level were significantly associated with poorer OS. In 16 patients with ascites, the amount of ascites increased in the course of the disease, and these were considered to be cancerous clinically, regardless of the amount. A minute amount of ascites and CA19-9 were important prognostic factors in CRT. Any amount of ascites was considered an early indicator of peritoneal carcinomatosis in LAPC. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Prognostic significance of microRNA-101 in solid tumor: A meta-analysis.

    PubMed

    Ma, Xianxiong; Bai, Jie; Xie, Gengchen; Liu, Yulin; Shuai, Xiaoming; Tao, Kaixiong

    2017-01-01

    MicroRNA-101 has been reported as an important factor in carcinogenesis of several malignant tumors. However, its actual role in prognosis among solid malignancies remains unclear. Accordingly, we performed this meta-analysis aiming to identify prognostic significance of miR-101 in solid tumor. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or disease-free survival (DFS)/metastasis-free survival (MFS)/progression-free survival (PFS)/relapse-free survival (RFS)/time-to progression (TTP) were estimated with random effects or fixed effects models on the basis of heterogeneity. Subgroup analysis, sensitive analysis and meta-regression analysis were also conducted to clarify the possible confounding factors and investigate the source of heterogeneity. Publication bias was evaluated by using Begg's and Egger's tests. A total of 21 studies containing 3753 cases were selected into our quantitative analysis via electronic database search. A lower expression of miR-101 was significantly associated with worse OS (HR = 0.66, 95%CI [0.52-0.85], P = 0.001) and PFS (HR = 0.70, 95%CI [0.51-0.95], P = 0.023) in patients with solid tumor. The under-expression of miRNA-101 is a credible indicator of poorer prognosis in several of solid malignancies.

  2. Marital status is an independent prognostic factor for tracheal cancer patients: an analysis of the SEER database

    PubMed Central

    Li, Mu; Dai, Chen-Yang; Wang, Yu-Ning; Chen, Tao; Wang, Long; Yang, Ping; Xie, Dong; Mao, Rui; Chen, Chang

    2016-01-01

    Background Although marital status is an independent prognostic factor in many cancers, its prognostic impact on tracheal cancer has not yet been determined. The goal of this study was to examine the relationship between marital status and survival in patients with tracheal cancer. Results Compared with unmarried patients (42.67%), married patients (57.33%) had better 5-year OS (25.64% vs. 35.89%, p = 0.009) and 5-year TCSS (44.58% vs. 58.75%, p = 0.004). Results of multivariate analysis indicated that marital status is an independent prognostic factor, with married patients showing better OS (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64–0.95, p = 0.015) and TCSS (HR = 0.70, 95% CI 0.54–0.91, p = 0.008). In addition, subgroup analysis suggested that marital status plays a more important role in the TCSS of patients with non-low-grade malignant tumors (HR = 0.71, 95% CI 0.53–0.93, p = 0.015). Methods We extracted 600 cases from the Surveillance, Epidemiology, and End Results (SEER) database. Variables were compared by Pearson chi-squared test, t-test, log-rank test, and multivariate Cox regression analysis. Overall survival (OS) and tracheal cancer-specific survival (TCSS) were compared between subgroups with different pathologic features and tumor stages. Conclusions Marital status is an independent prognostic factor for survival in patients with tracheal cancer. For that reason, additional social support may be needed for unmarried patients, especially those with non-low-grade malignant tumors. PMID:27780931

  3. Prognostic significance of mucin expression profiles in breast carcinoma with signet ring cells: a clinicopathological study.

    PubMed

    Ohashi, Ryuji; Hayama, Ayako; Yanagihara, Keiko; Yamashita, Koji; Sakatani, Takashi; Takei, Hiroyuki; Naito, Zenya

    2016-11-15

    Signet ring cells (SRCs) often accompany gastrointestinal carcinoma, referred to as SRC carcinoma; however, breast cancers containing SRCs have not been well characterized, leaving the prognostic significance of SRCs undetermined. We have described clinicopathological characteristics of patients with breast cancer containing SRCs in relation to the expression levels of MUC1, MUC2, MUC4, MUC5AC, and MUC6. Twenty-two breast cancer cases with variable degrees of SRC population were retrospectively studied. Each case was categorized as high (>31 %) or low (<30 %) SRC tumor. The SRCs were morphologically classified into the intra-cytoplasmic lumen (ICL) type, or the non-ICL type. The expression levels of MUC1, MUC2, MUC4, MUC5AC and MUC6 were determined immunohistochemically. Depending on its subcellular localization, MUC1 was categorized as the luminal and cytoplasmic (LC) type, or the cytoplasmic with circumferential membranous accentuation (CM) type. These histological findings were compared with other clinicopathological parameters. The series consisted of invasive ductal carcinoma (n = 9), invasive lobular carcinoma (n = 9), and mucinous carcinoma (n = 4) cases. The SRC population accounted for 8-81 % of the tumor cells. Eight cases had ICL type SRCs, and the remaining 14 had non-ICL type SRCs. Neither the high (n = 12) and low (n = 10) percentage of SRCs, nor the SRC types affected the clinicopathological parameters. In the low MUC1 group (n = 11), larger tumors, higher nuclear grade, lymph node metastasis, and negativity for estrogen receptor was more frequently identified compared to the high MUC1 group (n = 11; p = 0.01, p = 0.002, p = 0.008, and p = 0.02, respectively). The CM group (n = 7) had more patients with large-sized tumors, lymph node metastasis, lymphovascular invasion, and higher Ki67 indices than the LC group (n = 15; p = 0.04, p = 0.001, p = 0.006, and p = 0.03, respectively

  4. 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

  5. Prognostic significance of HLA class I and II expression in patients with diffuse large B cell lymphoma treated with standard chemoimmunotherapy.

    PubMed

    Tada, Kohei; Maeshima, Akiko Miyagi; Hiraoka, Nobuyoshi; Yamauchi, Nobuhiko; Maruyama, Dai; Kim, Sung-Won; Watanabe, Takashi; Katayama, Naoyuki; Heike, Yuji; Tobinai, Kensei; Kobayashi, Yukio

    2016-10-01

    Loss of tumor cell human leukocyte antigen (HLA) is an immune escape mechanism for malignancies. However, the effect of low HLA class I or class II expression in diffuse large B cell lymphoma (DLBCL) treated with chemoimmunotherapy with the monoclonal antibody rituximab is largely unknown. We retrospectively analyzed samples and other data from 144 patients with DLBCL who were newly diagnosed in our institution and treated with standard R-CHOP therapy. We used antibodies against pan-HLA class I and pan-HLA class II molecules to assess HLA expression and its effect on prognosis. In a multivariate analysis, loss of HLA class II expression was a significantly independent adverse factor for progression-free survival (PFS; hazard ratio 2.3; 95 % confidence interval 1.2-4.6; P = 0.01). Although HLA class I loss of expression did not correlate with prognosis, the combination of HLA class I(+) with either low peripheral lymphocyte count or CD3(+) lymphocyte count was an adverse prognostic factor for PFS. Loss of HLA class II is an International Prognostic Index (IPI)-independent adverse factor for PFS in patients with DLBCL treated with standard therapy. However, in contrast to other solid cancers, HLA class I loss was not solely a prognostic factor in DLBCL.

  6. Overexpressed HDGF as an independent prognostic factor is involved in poor prognosis in Chinese patients with liver cancer

    PubMed Central

    2010-01-01

    Background Hepatoma-derived growth factor (HDGF) is involved in the hepatocarcinogenesis. In this study, we investigated the HDGF expression in hepatocellular carcinoma (HCC) and its correlation with clinicopathologic features, including the survival of patients with HCC. Furthermore, we examined the biological processes regulated by HDGF during the development of using HepG2 cell line as a model system. Methods we used immunohistochemistry to compare HDGF protein expression in HCC and normal liver tissues and further analyze the HDGF protein expression in clinicopathologically characterized 137 HCC cases. We stably knocked down the endogenous expression level of HDGF in HepG2 cells with specific shRNA-expressing lentiviral vector. Following the successful establishment of stable cells, we examined in vitro cell growth by MTT assay, anchorage-independent growth by soft-agar colony formation assay and cell migration/invasion by transwell and boyden chamber assay. And in addition, we also investigated the in vivo tumor growth by xenograft transplantation of HepG2 cells into nude mice. Results Protein expression level of HDGF was markedly higher in HCC tissues than that in the normal liver tissues(P = 0.011). In addition, high expression of HDGF protein was positively correlated with T classification(p < 0.001), N classification (p < 0.001), and clinical stage (p < 0.001) of HCC patients. Patients with higher HDGF expression showed a significantly shorter overall survival time than did patients with low HDGF expression. Multivariate analysis suggested that HDGF expression might be an independent prognostic indicator(p < 0.001) for the survival of patients with HCC. HDGF-specific shRNA (shHDGF) successfully knocked down its endogenous expression in HepG2 cells. Compared to the parental and control shRNA-transfected (shCtrl) HepG2 cells, the shHDGF cells exhibited significantly reduced in vitro cell growth, anchorage-independent growth, cell migration and invasion (p

  7. Overexpressed HDGF as an independent prognostic factor is involved in poor prognosis in Chinese patients with liver cancer.

    PubMed

    Zhou, Yanyan; Zhou, Nanxiang; Fang, Weiyi; Huo, Jirong

    2010-09-16

    Hepatoma-derived growth factor (HDGF) is involved in the hepatocarcinogenesis. In this study, we investigated the HDGF expression in hepatocellular carcinoma (HCC) and its correlation with clinicopathologic features, including the survival of patients with HCC. Furthermore, we examined the biological processes regulated by HDGF during the development of using HepG2 cell line as a model system. We used immunohistochemistry to compare HDGF protein expression in HCC and normal liver tissues and further analyze the HDGF protein expression in clinicopathologically characterized 137 HCC cases. We stably knocked down the endogenous expression level of HDGF in HepG2 cells with specific shRNA-expressing lentiviral vector. Following the successful establishment of stable cells, we examined in vitro cell growth by MTT assay, anchorage-independent growth by soft-agar colony formation assay and cell migration/invasion by transwell and boyden chamber assay. And in addition, we also investigated the in vivo tumor growth by xenograft transplantation of HepG2 cells into nude mice. Protein expression level of HDGF was markedly higher in HCC tissues than that in the normal liver tissues(P = 0.011). In addition, high expression of HDGF protein was positively correlated with T classification(p < 0.001), N classification (p < 0.001), and clinical stage (p < 0.001) of HCC patients. Patients with higher HDGF expression showed a significantly shorter overall survival time than did patients with low HDGF expression. Multivariate analysis suggested that HDGF expression might be an independent prognostic indicator(p < 0.001) for the survival of patients with HCC. HDGF-specific shRNA (shHDGF) successfully knocked down its endogenous expression in HepG2 cells. Compared to the parental and control shRNA-transfected (shCtrl) HepG2 cells, the shHDGF cells exhibited significantly reduced in vitro cell growth, anchorage-independent growth, cell migration and invasion (p < 0.05). In vivo, the

  8. 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.

  9. Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

    PubMed

    Karatas, Fatih; Erdem, Gokmen Umut; Sahin, Suleyman; Aytekin, Aydin; Yuce, Deniz; Sever, Ali R; Babacan, Taner; Ates, Ozturk; Ozisik, Yavuz; Altundag, Kadri

    2017-04-01

    The relation between higher body mass index (BMI) and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a controversial issue according to the data of Western and Asian patients. The aim of this study is to evaluate BMI and pCR to NAC and discuss the importance of pCR outcomes in Turkish BC patients as a bridging country between Europe and Asia. Of the 4423 BC patients diagnosed between the years 1994 and 2015 in Hacettepe University Cancer Institute, 295 female patients with stage II and III BC were enrolled in the study. Three different group divisions were done according to patients' BMI as normal or underweight (N/U) patients (BMI <25 kg/m(2)), overweight (OW) patients (BMI = 25-29.9 kg/m(2)) and obese (OB) patients (BMI ≥30 kg/m(2)). BC subtypes were defined as luminal-like (ER/PR-positive and HER2-negative), HER2/luminal (ER/PR-positive and HER2-positive), HER2-type (ER/PR-negative and HER2-positive), and triple-negative (TNBC; ER/PR- and HER2-negative). The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed according to Kaplan-Meier method. The Log-rank test was used to compare the subgroup analysis and logistic regression analysis to determine the independent prognostic factors. In this study, a total number of 93 (31.5%) patients were N/U, 107 (36.3%) patients were OW and 95 (32.2%) patients were OB. Among groups, except for the age, no baseline clinicopathological differences were found. In 70 (23.7%) patients, pCR was achieved. pCR rates in N/U, OW and OB were 31.2%, 22.4%, and 17.9% respectively, showing a considerable trend towards significance (P = 0.09 in chi-square test). In the multivariate logistic regression analysis, obesity was an independent adverse prognostic feature on pCR to NAC compared to N/U patients (OR, 0.34; 95% CI, 0.13 to 0.85, P = 0.02). The recurrence rates were slightly increased with the increase of BMI (N/U = 24.7%, OW = 29.0% and OB

  10. Prognostic significance of lymphatic, vascular and perineural invasion for bladder cancer patients treated by radical cystectomy.

    PubMed

    Muppa, Prasuna; Gupta, Sounak; Frank, Igor; Boorjian, Stephen A; Karnes, R Jeffrey; Thompson, R Houston; Thapa, Prabin; Tarrell, Robert F; Herrera Hernandez, Loren P; Jimenez, Rafael E; Cheville, John C

    2017-04-01

    In radical cystectomy specimens with bladder cancer, lymphatic and vascular invasion are often reported as 'angiolymphatic' or 'lymphovascular' invasion, terms that combine the findings of tumour within simple endothelial-lined lymphatic spaces and tumour within muscle-lined blood vessels. It is unclear if these patterns of invasion have different prognostic significance. In addition, there are conflicting data regarding the significance of lymphatic, vascular and perineural invasion in patients with bladder cancer. Herein, we studied 1504 patients treated by radical cystectomy for bladder cancer at our institution and followed for a mean of 10.6 years. Cases were re-reviewed by a urological pathologist for lymphatic invasion defined as tumour within a non-muscle-lined endothelial-lined lymphatic space, vascular invasion defined as tumour in a muscle-lined blood vessel, and perineural invasion defined as tumour within the perineural sheath. Associations of clinical and pathological features with bladder cancer death were evaluated using Cox proportional hazards regression models and summarised with hazard ratios and 95% confidence intervals. Survival was estimated by the Kaplan-Meier method. Multivariate analysis showed that lymphatic and vascular invasion but not perineural invasion were significantly associated with cancer specific survival (p<0.0001 and p=0.02, respectively). There was a significant association of lymphatic and vascular invasion but not perineural invasion with involved regional lymph nodes (p<0.0001 and p=0.004, respectively). In patients with metastasis to regional lymph nodes, lymphatic invasion remained significantly associated with outcome (p=0.02). The frequency of lymphatic and vascular invasion varied amongst histological subtypes of bladder cancer. Vascular and lymphatic invasion should be clearly defined and reported for radical cystectomy specimens containing bladder cancer. Copyright © 2017 Royal College of Pathologists of

  11. Prognostic significance of blood pressure measured in the office, at home and during ambulatory monitoring in older patients in general practice.

    PubMed

    Fagard, R H; Van Den Broeke, C; De Cort, P

    2005-10-01

    The purpose of the study was to assess the prognostic significance of out-of-the-office blood pressure (BP) measurement in older patients in general practice, and to compare the results for BP measured in the office, at home and during 24-h ambulatory monitoring. All registerd patients who were 60 years or older were eligible for the study, except when bedridden, demented or admitted in a home for sick elderly people, or when they had suffered a myocardial infarction or stroke. After baseline measurements in 1990-1993, incidence of major cardiovascular events (cardiovascular death, myocardial infarction and stroke) was ascertained in 2002-2003 and related to the BPs by use of multivariate Cox regression analysis. Age of the 391 patients averaged 71+/-9 years; 40% were men. During median follow-up of 10.9 years, 86 patients (22%) suffered a cardiovascular event. The adjusted relative hazard rate, associated with a 1 s.d. increment in systolic BP was 1.13 for office BP (NS), and, respectively, 1.32, 1.33 and 1.42, for home, daytime and night time BP (P< or =0.01 for all). Results were similar for diastolic BP. The prognostic significance of all out-of-the-office BPs was independent of office BP. The prognostic value of home BP was equal to (systolic) or even better (diastolic) than that of daytime BP. Night time BP predicted cardiovascular events independent of all other BPs. Prognosis of white-coat hypertension was similar to that of true normotension, but better than in sustained hypertension. In conclusion, the prognostic value of home BP is better than that of office BP in older patients in primary care, and is at least equal to that of daytime ambulatory BP. The prognosis of patients with white-coat hypertension is similar to that of true normotensives.

  12. Pretreatment Quality of Life Is an Independent Prognostic Factor for Overall Survival in Patients with Advanced Stage Non-small Cell Lung Cancer

    PubMed Central

    Qi, Yingwei; Schild, Steven E.; Mandrekar, Sumithra J.; Tan, Angelina D.; Krook, James E.; Rowland, Kendrith M.; Garces, Yolanda I.; Soori, Gamini S.; Adjei, Alex A.; Sloan, Jeff A.

    2010-01-01

    Hypothesis We conducted this pooled analysis to assess the prognostic value of pretreatment Quality of Life (QOL) assessments on overall survival (OS) in advanced non-small cell lung cancer (NSCLC). Methods Four hundred twenty patients with advanced NSCLC (stages IIIB with pleural effusion and IV) from six North Central Cancer Treatment Group trials were included in this study. QOL assessments included the single-item Uniscale (355 patients), Lung Cancer Symptom Scale (217 patients), and Functional Assessment of Cancer Therapy-Lung (197 patients). QOL scores were transformed to a 0 to 100 scale with higher scores representing better status and categorized using the sample median or clinically deficient score (CDS, ≤50 versus >50). Cox proportional hazards models stratified by study were used to evaluate the prognostic importance of QOL on OS alone and in the presence of other prognostic factors such as performance status, age, gender, body mass index, and laboratory parameters. Results Pretreatment QOL accessed by Uniscale was significantly associated with OS univariately (p < 0.0001). Uniscale (p < 0.0001; hazard ratio = 1.6 for the sample median and 2.0 for the CDS categorization) and body mass index were the only significant predictors of OS multivariately. The median survival of patients who had a Uniscale score less than or equal to the CDS (≤50) was 5.7 versus 11.1 months for the >50 group; and 7.8 versus 13 months for the less than or equal to sample median (≤83) group and >83 group, respectively. The Lung Cancer Symptom Scale and the Functional Assessment of Cancer Therapy-Lung total scores were not significant predictors of OS. Conclusions Pretreatment QOL measured by Uniscale is a significant and an independent prognostic factor for OS, and QOL should be routinely integrated as a stratification factor in advanced NSCLC trials. PMID:19546817

  13. 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

  14. Prognostic significance of calcified plaque among symptomatic patients with nonobstructive coronary artery disease

    PubMed Central

    Shah, Sana; Bellam, Naveen; Leipsic, Jonathon; Berman, Daniel S.; Quyyumi, Arshed; Hausleiter, Jörg; Achenbach, Stephan; Al-Mallah, Mouaz; Budoff, Matthew J.; Cademartiri, Fillippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Chow, Benjamin J. W.; Cury, Ricardo C.; Delago, Augustin J.; Dunning, Allison L.; Feuchtner, Gudrun M.; Hadamitzky, Martin; Karlsberg, Ronald P.; Kaufmann, Philipp A.; Lin, Fay Y.; Chinnaiyan, Kavitha M.; Maffei, Erica; Raff, Gilbert L.; Villines, Todd C.; Gomez, Millie J.; Min, James K.; Shaw, Leslee J.

    2015-01-01

    Background Coronary artery calcium (CAC) is a well-established predictor of clinical outcomes for population screening. Limited evidence is available as to its predictive value in symptomatic patients without obstructive coronary artery disease (CAD). The aim of the current study was to assess the prognostic value of CAC scores among symptomatic patients with nonobstructive CAD. Methods From the COronary Computed Tomographic Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 7,200 symptomatic patients with nonobstructive CAD (<50% coronary stenosis) on coronary-computed tomographic angiography were prospectively enrolled and followed for a median of 2.1 years. Patients were categorized as without (0% stenosis) or with (>0% but <50% coronary stenosis) a luminal stenosis. CAC scores were calculated using the Agatston method. Univariable and multivariable Cox proportional hazard models were employed to estimate all-cause mortality and/or myocardial infarction (MI). Four-year death and death or MI rates were 1.9% and 3.3%. Results Of the 4,380 patients with no luminal stenosis, 86% had CAC scores of <10 while those with a luminal stenosis had more prevalent and extensive CAC with 31.9% having a CAC score of ≥100. Among patients with no luminal stenosis, CAC was not predictive of all-cause mortality (P = .44). However, among patients with a luminal stenosis, 4-year mortality rates ranged from 0.8% to 9.8% for CAC scores of 0 to ≥400 (P < .0001). The mortality hazard was 6.0 (P = .004) and 13.3 (P < .0001) for patients with a CAC score of 100–399 and ≥400. In patients with a luminal stenosis, CAC remained independently predictive in all-cause mortality (P < .0001) and death or MI (P < .0001) in multivariable models containing CAD risk factors and presenting symptoms. Conclusions CAC allows for the identification of those at an increased hazard for death or MI in symptomatic patients with nonobstructive disease. From the

  15. Prognostic Significance of Modified Advanced Lung Cancer Inflammation Index (ALI) in Patients with Small Cell Lung Cancer_ Comparison with Original ALI

    PubMed Central

    Kim, Young Saing; Seo, Ja-Young; Park, Inkeun; Ahn, Hee Kyung; Jeong, Yu Mi; Kim, Jeong Ho

    2016-01-01

    Background Advanced lung cancer inflammation index (ALI, body mass index [BMI] x serum albumin/neutrophil-lymphocyte ratio [NLR]) has been shown to predict overall survival (OS) in small cell lung cancer (SCLC). CT enables skeletal muscle to be quantified, whereas BMI cannot accurately reflect body composition. The purpose was to evaluate prognostic value of modified ALI (mALI) using CT-determined L3 muscle index (L3MI, muscle area at L3/height2) beyond original ALI. Methods L3MIs were calculated using the CT images of 186 consecutive patients with SCLC taken at diagnosis, and mALI was defined as L3MI x serum albumin/NLR. Using chi-squared test determined maximum cut-offs for low ALI and low mALI, the