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Independent Prognostic Factor (independent + prognostic_factor)
Kinds of Independent Prognostic Factor Selected AbstractsRelation of microvessel density with microvascular invasion, metastasis and prognosis in renal cell carcinomaBJU INTERNATIONAL, Issue 6 2008Esin Yildiz OBJECTIVE To clarify the significance of microvessel density (MVD) in a retrospective investigation the relationship between the pattern of MVD (reflecting angiogenesis), and tumour stage, grade, size, and occurrence of microvessel invasion (MVI), metastasis, and cancer-specific survival (CSS) in patients who had surgery for renal cell carcinoma (RCC). PATIENTS AND METHODS Vessels were labelled in sections of formalin-fixed, paraffin-embedded tissues from 54 RCCs by CD34 immunohistochemistry. The mean MVD, expressed as the number of vessels per 10 high-power fields (HPF, ×400) were measured for each case. In addition, all pathological slides were reviewed for the presence and absence of MVI. The prognostic value of MVD and MVI was then evaluated, and correlated with the usual prognostic variables, tumour metastasis and CSS. RESULTS In a univariate analysis of CSS, the MDV tended to be lower as stage increased from pT1 to pT3, and as grade increased from G1 to G4, although it was statistically significant only for stage (P < 0.001 and 0.050, respectively). The mean MVD was higher in 42 nonmetastatic than in 12 metastatic tumours, and in 33 tumours associated with MVI than in 21 with no MVI (P < 0.001). The mean MVD was also lower and significantly different for 28 large than 26 small tumours (P = 0.005). The survival rate of patients with tumours that were small, low-stage, of higher MVD, with no MVI and metastasis was significantly higher than that of patients with large, high-stage, low MVD, with MVI and metastatic tumours (all P < 0.001). MVI was significantly more common with a decreasing trend in MVD and the presence of metastasis (Spearman rank correlation rs = ,0.68, P = 0.01, and rs = 0.39, P = 0.01, respectively). Independent prognostic factors in a multivariate analysis were: in all patients with RCC, tumour stage (P = 0.013) and metastasis (P = 0.028); in those with low MVD, MVI (P = 0.004) and metastases (P = 0.016); in those with no MVI, stage (P = 0.020); in those with MVI, MVD (P = 0.001); in those with no metastases, stage (P = 0.045); and in those with metastases, MVD (P < 0.001). No independent predictor was identified in patients with high MVD. In patients with no metastases there was a significantly shorter median CSS time in RCCs with low MVD and with MVI (P = 0.004 for both). Similarly, patients who had grade 3,4 tumours, vs those with lower MVD and with MVI, had a significantly shorter median CSS (P = 0.020 for MVD, and 0.01 for MVI). CONCLUSIONS This study suggested that MVD in RCC was inversely associated with MVI, tumour metastasis, patient survival and tumour diameter and stage, from the usual prognostic variables, but MVD was not an independent prognostic factor in multivariate analysis for all patients with RCC. Low MVD and the presence of MVI appears to be a marker for identifying patients with an adverse prognosis. [source] Bone marrow cells from myelodysplastic syndromes show altered immunophenotypic profiles that may contribute to the diagnosis and prognostic stratification of the disease: A pilot study on a series of 56 patients,CYTOMETRY, Issue 3 2010Sergio Matarraz Abstract A heterogeneous spectrum of immunophenotypic abnormalities have been reported in myelodysplastic syndromes (MDS). However, most studies are restricted to the analysis of CD34+ cells and/or other major subsets of CD34, cells, frequently not exploring the diagnostic and prognostic impact of immunophenotyping. Methods: We propose for the first time an immunophenotypic score (IS) based on the altered distribution and immunophenotypic features of maturing/mature compartments of bone marrow (BM) hematopoietic cells in 56 patients with MDS that could contribute to a refined diagnosis and prognostic evaluation of the disease. Results: Although MDS-associated phenotypes were detected in reactive BM, the overall immunophenotypic profile of BM cells allowed an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected per patient were simultaneously considered in the proposed IS. Interestingly, increasingly higher IS were found among patients with MDS showing adverse prognostic factors and in low- versus high-grade cases. The most informative prognostic factors included the number of CD34+ cells, presence of aberrant CD34,/CD117+ precursors, decreased mature neutrophils and CD34, erythroid precursors, and increased numbers of CD36,/lo erythroid precursors; in addition, the IS was an independent prognostic factor for overall survival. Conclusions: Assessment of immunophenotypic abnormalities of maturing/mature BM cells allows an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected are simultaneously scored. Interestingly, progressively higher IS were found among patients with MDS with adverse prognostic features and shorter overall survival. © 2010 Clinical Cytometry Society [source] Plasma matrix metalloproteinase-3 level is an independent prognostic factor in stable coronary artery diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2005T. C. Wu Abstract Background, Recent evidence suggests the important role of matrix metalloproteinases (MMPs) in the progression of atherosclerosis and development of clinical events. We assessed the prognostic value of different plasma MMPs in patients with stable coronary artery disease (CAD). Materials and methods, A total of 165 consecutive nondiabetic patients with angiographically significant CAD (n = 150) or normal coronary angiograms despite exercise-induced myocardial ischemia (cardiac syndrome X, n = 15) and 17 normal subjects were evaluated. In each subject, plasma inflammatory markers including high sensitivity C-reactive protein (hsCRP) and MMP-2, 3 and 9 were measured. In CAD patients, major cardiovascular events including cardiac death, nonfatal myocardial infarction, unscheduled coronary revascularization and hospitalization as a result of unstable angina were prospectively followed up for more than 6 months. Results, Plasma levels of MMPs were significantly higher in CAD patients than in those with cardiac syndrome X and in normal subjects (MMP-2: 914·76 ± 13·20 vs. 830·79 ± 31·95 vs. 783·08 ± 28·40 ng mL,1, P = 0·002; MMP-3: 129·59 ± 4·21 vs. 116·86 ± 8·09 vs. 91·71 ± 9·55 ng mL,1, P = 0·011; MMP-9: 31·42 ± 2·84 vs. 11·40 ± 5·49 vs. 6·71 ± 2·89 ng mL,1, P = 0·006). In CAD patients, there were 48 major cardiovascular events during a mean follow-up period of 17·74 ± 0·85 months. The numbers of diseased vessels (HR = 2·19, 95% CI 1·20,1·02, P = 0·011), plasma hsCRP (HR = 2·21, 95% CI 1·18,4·11, P = 0·013) and MMP-3 level (HR = 2·46, 95% CI = 1·15,5·28, P = 0·021) were associated with the development of cardiovascular events. However, only the plasma MMP-3 level was an independent predictor of the adverse events in CAD patients (HR = 2·47, 95% CI 1·10,5·54, P = 0·028). Conclusions, Plasma MMP levels were increased in CAD patients. Plasma MMP-3 level, rather than hsCRP, was an independent prognostic marker for future cardiovascular events, suggesting its potential role in risk stratification and clinical management of stable CAD. [source] MDM2 SNP309 promoter polymorphism, an independent prognostic factor in chronic lymphocytic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Kerstin Willander Abstract Background:, The single nucleotide polymorphism SNP309 with a change from T to G in the promoter region of the MDM2 gene is shown to increase the MDM2 protein levels and attenuate the p53 levels and associates with disease progression in several tumors. Objective:, In this study, the role of the polymorphism was investigated with regard to the clinical outcome in B-cell chronic lymphocytic leukemia (B-CLL). Patients:, A total of 210 patients with B-CLL were followed for up to 19 yr. Results:, The overall survival (OS) of patients with at least one G-allele was significantly shorter when compared with those with two T-alleles (P = 0.024) with a more pronounced difference in patients below the median age. Age at onset of B-CLL was similar irrespective of MDM2 status. The presence of a G-allele in combination with TP53 mutations or unmutated IgVH gene status resulted in an additive risk of death. Conclusion:, In this report, with a high proportion of B-CLL patients with an advanced Binet stage and with an unmutated IgVH gene, MDM2 SNP309 was found to be independently associated with OS. The survival difference was more pronounced in younger patients. [source] Proliferative activity and diagnostic delay in oral cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 10 2010Juan Seoane PhD Abstract Background Tumor stage may relate to the chronology of neoplasm growth and has been used as an outcome variable when studying diagnostic delay in oral cancer. However, tumor growth rate may act as a confounding factor. Methods We reviewed a total of 63 incident cases of oral cancer. The variables considered for the study included age, sex, smoking history, tumor site, TNM stage, Ki-67 score, and diagnostic delay. Results Significant differences between survivors and exitus were found in terms of tumor stage at diagnosis (I,II vs III,IV), sex, and Ki-67 scores. When the analysis was adjusted for tumor stage at diagnosis (I,II vs III,IV), proliferative activity resulted to be an independent prognostic factor for survival, whereas diagnostic delay did not influence survival. Conclusion These results seem to suggest that survival from oral cancer is affected more by the biology of the cancer (rapid tumor growth) than by diagnostic delay. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [source] Postradiation nasopharyngeal necrosis in the patients with nasopharyngeal carcinoma,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2009Yi-Jun Hua MD Abstract Background Radiation-induced nasopharyngeal necrosis is a consequential late effect in the patients with nasopharyngeal carcinoma (NPC). Patients with NPC who have been treated with high-dose radiotherapy are at risk of developing postradiation nasopharyngeal necrosis (PRNN). However, the analysis of PRNN with a significant cohort of patients has not been reported in English-language literature. In this study, we aimed to evaluate PRNN in 28 patients with NPC. Methods From June 2006 to December 2007, 28 patients were diagnosed with PRNN with pathologic evidence. Surgical procedure of endoscopy-guided debridement and systemic anti-inflammatory treatments were conducted for the patients. Their clinical features, treatment procedures, and outcomes were analyzed retrospectively. Results Clinical symptoms such as foul odor and headache were alleviated in all, 8 patients were cured of their PRNN, 9 patients with exposed internal carotid artery died of sudden nasopharyngeal massive bleeding, and 3 patients died of exhaustion (cachexia). Conclusion PRNN is an important consequential late effect of radiotherapy in the patients with NPC. Internal carotid artery erosion is a severe situation and acts as an independent prognostic factor for the patients. Diagnosis of PRNN could be made after ruling out the persistent-recurrent NPC proven by pathologic examination. Surgery is effective for improving the quality of life and for curing PRNN. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Clinical significance of osteopontin expression in T1 and T2 tongue cancersHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 6 2008Chih-Yen Chien MD Abstract Background Osteopontin (OPN) is considered to be a tumor-related protein associated with tumor aggressiveness and metastasis. Methods Immunohistochemistry was used to study the clinical significance of OPN expression in T1 and T2 tongue cancers. Results Positive OPN expression significantly correlated with higher tumor classification (T) (p = .004), positive nodal classification (N) (p < .001), greater tumor thickness (p < .001), and presence of tumor necrosis (p = .016), respectively. The unfavorable cumulative 5-year disease-free survival rate significantly correlated with positive OPN expression (p < .001), T2 (p = .024), positive N (p < .001), greater tumor thickness (p = .023), and positive tumor necrosis (p = .003). However, taking CD105 into consideration, only CD105 expression was the independent prognostic factor for survival by Cox's regression analysis. Conclusion Overexpression of OPN in the tumors implicated a more aggressive tumor behavior and was an important factor for survival. In addition, there might be relationship between OPN and CD105 expressions in angiogenesis. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Primary and secondary small cell neuroendocrine carcinoma of the larynx: A reviewHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2008Alfio Ferlito MD, DPath, FASCP, FDSRCS, FHKCORL, FRCPath, FRCSEd, FRCSGlasg, FRCSI Abstract Primary laryngeal small cell neuroendocrine carcinoma (SCNC) is an unusual malignancy accounting for <0.5% of laryngeal carcinomas. To date, approximately 200 cases of primary and 5 of secondary SCNC of the larynx have been reported. This tumor most often presents in the sixth and seventh decades in men who are heavy cigarette smokers. The lesion may be associated with different paraneoplastic syndromes (ectopic adrenocorticotropic hormone syndrome, Schwartz,Bartter syndrome or syndrome of inappropriate secretion of antidiuretic hormone, and Eaton,Lambert myasthenic syndrome) or with ectopic hormone production. The diagnosis is based essentially on the histologic appearance of the tumor, confirmed by immunocytochemical investigations. Concurrent chemoradiotherapy regimens offer potential for long-term survival. This tumor is biologically aggressive, and the extent of the disease is the most significant independent prognostic factor of survival. The survival rate is similar to that with pulmonary SCNC. © 2008 Wiley Periodicals, Inc. Head Neck, 2008 [source] Impact of nutrition support on treatment outcome in patients with locally advanced head and neck squamous cell cancer treated with definitive radiotherapy: A secondary analysis of RTOG trial 90-03,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 4 2006Rachel Rabinovitch MD Abstract Background. The aim was to evaluate the relationship between nutrition support (NS) on host toxicity and cancer outcome in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing definitive radiotherapy (XRT). Methods. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 90-03, a prospective randomized trial evaluating four definitive XRT fractionation schedules in patients with locally advanced HNSCC, which prospectively collected data on NS delivered before treatment (BNS), during treatment (TNS), and after definitive XRT. NS data and pretreatment characteristics of the 1073 evaluable patients were analyzed against therapy toxicity and outcome. Results. Patients receiving BNS experienced significantly less weight loss by the end of treatment and less grade 3 to 4 mucositis than patients not receiving BNS. However, patients receiving BNS had a poorer 5-year actuarial locoregional control rate than patients receiving TNS or no NS (29%, 55%, and 57%, respectively, p < .0001) and a poorer 5-year overall survival rate (16%, 36%, and 49%, respectively, p < .0001). Patients receiving BNS were significantly more likely to have a higher T classification, N status, and overall American Joint Committee on Cancer (AJCC) stage and initial presentation with greater pretreatment weight loss, and a poorer Karnofsky Performance Status (KPS) than patients not receiving BNS. After adjusting for the impact of these prognostic factors through a recursive partition analysis, a multivariate analysis with a stratified Cox model found that BNS was still a highly significant independent prognostic factor for increased locoregional failure (hazards ratio [HR], 1.47; 95% confidence interval [CI], 1.21,1.79; p < .0001) and death (HR, 1.41; 95% CI, 1.19,1.67; p < .0001). Conclusion. In this study, the largest prospective evaluation of nutrition data in treated patients with cancer, BNS was associated with inferior treatment outcome in the patients with HNSCC undergoing XRT. These results should be considered hypothesis generating and encourage prospective clinical research and identification of the mechanisms underlying this finding. © 2005 Wiley Periodicals, Inc. Head Neck28: 287,296, 2006 [source] Proteomic profiling reveals the prognostic value of adenomatous polyposis coli,end-binding protein 1 in hepatocellular carcinoma,HEPATOLOGY, Issue 6 2008Tatsuya Orimo Histological differentiation is a major pathological parameter associated with poor prognosis in patients with hepatocellular carcinoma (HCC) and the molecular signature underlying HCC differentiation may involve key proteins potentially affecting the malignant characters of HCC. To develop prognostic biomarkers for HCC, we examined the global protein expression profiles of 45 surgically resected tissues, including 27 HCCs with different degree of histological differentiation, 11 adjacent nontumor tissues, and seven normal liver tissues. Unsupervised classification grouped the 45 samples according to their histological classification based on the protein expression profiles created by laser microdissection and two-dimensional difference gel electrophoresis (2D-DIGE). Statistical analysis and mass spectrometry identified 26 proteins with differential expression, of which 14 were functionally linked to c-Myc, AP-1, HIF1A, hepatocyte nuclear factor 4 alpha, or the Ras superfamily (RhoA, CDC42, and Rac1). Among the proteins identified, we focused on APC-binding protein EB1 (EB1) because it was dominantly expressed in poorly differentiated HCCs, which generally correlate with the poor prognosis in patients with HCC. In addition, EB1 is controlled by c-Myc, RhoA, and CDC42, which have all been linked to HCC malignancy. Immunohistochemistry in a further 145 HCC cases revealed that EB1 significantly correlated with the degree of histological differentiation (P < 0.001), and univariate and multivariate analyses indicated that EB1 is an independent prognostic factor for recurrence (hazard ratio, 2.740; 95% confidence interval, 1.771,4.239; P < 0.001) and survival (hazard ratio, 2.256; 95% confidence interval, 1.337,3.807; P = 0.002) of patients with HCC after curative surgery. Conclusion: Proteomic profiling revealed the molecular signature behind the progression of HCC, and the prognostic value of EB1 in HCC. (HEPATOLOGY 2008;48:1851-1863.) [source] Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence,HEPATOLOGY, Issue 2 2008Ying-Hong Shi Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Despite significantly improved diagnosis and treatment in recent years, the long-term therapeutic effect is compromised by the frequent recurrence and metastasis, of which the molecular mechanisms are not fully understood. Our initial studies in established HCC cell lines with different metastatic capabilities indicated a correlation of metastasis with the resistance to apoptosis and therefore the ability to survive in stressed conditions. Subsequent investigation revealed that increased expression of X-linked inhibitor-of-apoptosis protein (XIAP) was correlated with the resistance to apoptosis and enhanced invasiveness in vitro, which could contribute to increased metastatic foci in vivo. Furthermore, we found that nearly 90% of clinical samples from advanced HCC patients expressed high levels of XIAP. Patients with XIAP-positive tumors had a significantly increased risk of relapse, which resulted from metastasis after total liver resection and orthotopic liver transplantation. Indeed, XIAP expression could be an independent prognostic factor for predicting disease-free survival rate and overall survival rate of these patients. XIAP expression was also highly correlated with advanced cases that exceeded the Milan criteria and could be a prognostic factor for disease-free survival in these patients as well. Conclusion: Our studies have shown an important molecule in controlling HCC metastasis, defined a biomarker that can be used to predict HCC recurrence and patient survival after treatment, and suggest that XIAP can be a molecular target subject to intervention to reduce metastasis and recurrence. (HEPATOLOGY 2008;48:497,507.) [source] Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinomaHISTOPATHOLOGY, Issue 2 2010Yun-Ching Chang Chang Y-C, Nieh S, Chen S-F, Jao S-W, Lin Y-L & Fu E (2010) Histopathology,57, 295,303 Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinoma Aims:, To test the validity of an invasive pattern grading score (IPGS) developed for oral squamous cell carcinoma (OSCC) as a prognostic indicator and to elucidate the relationship between the IPGS and clinical parameters. Methods and results:, The IPGS was applied to a total of 153 cases of OSCC. There were significant correlations between IPGS and distant metastasis (P = 0.01) or recurrence (P = 0.001). However, there were no significant correlations between IPGS and gender, age, size or extent, location, status of lymph node metastasis, clinical staging, or histological grading. Cases of OSCC with higher IPGS were associated with poor patient survival (P < 0.001) and higher probability of tumour recurrence (P = 0.001). Intraobserver (, = 0.74) and interobserver agreement (, = 0.67) were very satisfactory. Conclusions:, Our study confirms the validity of the IPGS, an indicator that is simple and easy to use. IPGS not only provides histological assessment of biological behaviour, but also offers an independent prognostic factor that may influence the treatment of OSCC. [source] Prognostic value of p27kip1 expression in adenocarcinoma of the pancreatic head regionHPB, Issue 3 2006Jerzy Mielko Abstract Background. p27kip1 is a tumour suppressor gene, functioning as a cyclin-dependent kinase inhibitor, and an independent prognostic factor in breast, colon, and prostate adenocarcinomas. Conflicting data are reported for adenocarcinoma of the pancreas. The aim of this study was to establish the prognostic value of p27kip1 expression in adenocarcinoma of the pancreatic head region. Patients and methods. The study included 45 patients (male/female ratio 2:1; mean age 59, range 38,82 years) with adenocarcinomas of the pancreatic head region: 24 , pancreatic head, 18 , periampullary and 3 , uncinate process. The patients underwent the Kausch-Whipple pancreatoduodenectomy (n=39), pylorus-preserving pancreatoduodenectomy (n=5), or nearly total pancreatectomy (n=1). Eight patients received adjuvant chemotherapy postoperatively. Follow-up time ranged from 3 to 60 months. Tumours were staged according to the pTNM classification (UICC 1997). Immunohistochemistry was done on paraffin-embedded blocks from tumour sections. Quantitative determination of p27kip1 expression was based on the proportion of p27kip1 -positive cells (< 5%= negative). Survival analysis was carried out using the Kaplan-Meier method and Cox regression model. Results. Positive p27kip1 expression was detected in 22 tumours (49%), whereas 23 tumours (51%) were p27kip1 -negative. There were no significant correlations between p27kip1 index and stage or lymph node involvement. Median survival time in patients with p27kip1 -positive tumours was 19 months, whereas in patients with p27kip1 -negative tumours it was 18 months (p=0.53). A significant relationship was found between p27kip1 -negative tumours and radical resection (p=0.04). Multivariate survival analysis revealed that the localization of the tumour (pancreatic head/uncinate process vs periampullary) was the only significant and independent prognosticator (p=0.01, Cox regression model). Resection margins involvement and grade remained nearly significant prognostic factors (p=0.07 and p=0.09, respectively). Conclusion. We conclude that p27kip1 has limited overall prognostic utility in resected carcinoma of the pancreatic head region, but its potential role as a marker of residual disease needs to be further assessed. [source] Lysyl oxidase expression is an independent marker of prognosis and a predictor of lymph node metastasis in oral and oropharyngeal squamous cell carcinoma (OSCC)INTERNATIONAL JOURNAL OF CANCER, Issue 11 2010Andrea Albinger-Hegyi Abstract Proteins of the lysyl oxidase (LOX) family are important modulators of the extracellular matrix. However, they have an important role in the tumour development as well as in tumour progression. To evaluate the diagnostic and prognostic value of the LOX protein in oral and oropharyngeal squamous cell carcinoma (OSCC) we performed QRT-PCR and immunohistochemical analysis on two tissue microarrays (622 tissue samples in total). Significantly higher LOX expression was detected in high grade dysplastic oral mucosa as well as in OSCC when compared to normal oral mucosa (P < 0.001). High LOX expression was correlated with clinical TNM stage (P = 0.020), lymph node metastases for the entire cohort (P < 0.001), as well as in the subgroup of small primary tumours (T1/T2, P < 0.001). Moreover, high LOX expression was correlated with poor overall survival (P = 0.004) and disease specific survival (P = 0.037). In a multivariate analysis, high LOX expression was an independent prognostic factor, predicting unfavourable overall survival. In summary, LOX expression is an independent prognostic biomarker and a predictor of lymph node metastasis in OSCC. Moreover, LOX overexpression may be an early phenomenon in the pathogenesis of OSCC and thus an attractive novel target for chemopreventive and therapeutic strategies. [source] Methylation of cystatin M promoter is associated with unfavorable prognosis in operable breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 12 2009Magdalini Kioulafa Abstract The methylation status of cystatin M (CST6) gene in breast tumors was investigated and its prognostic significance as a novel breast cancer biomarker was evaluated. Using methylation-specific PCR (MSP), CST6 promoter methylation was examined in 134 formalin fixed paraffin-embedded tissues (FFPEs): 10 pairs of breast tumors and their surrounding normal tissues, 10 breast fibroadenomas, 11 normal breast tissues and 93 breast tumors. Methylation of CST6 promoter was observed in 2/21 (9.5%) noncancerous breast tissues, 1/10 (10%) benign breast tumors (fibroadenomas) and 52 (55.9%) operable breast cancer tumor samples. CST6 was rarely methylated in the normal tissue surrounding the tumor (10%). During the follow-up period, 24 (25.8%) patients relapsed and 19 (20.4%) died. CST6 methylation was detected in 19 (79.2%) of patients who relapsed and in 15 (78.9%) of patients who died. Disease-free-interval (DFI) and overall survival (OS) were significantly associated with CST6 promoter methylation (p = 0.004 and p = 0.001 respectively). Multivariate analysis revealed that CST6 methylation is an independent prognostic factor for DFI (HR = 3.484; 95% CI: 1.155,10.511; p = 0.027). and OS (HR = 9.190; 95% CI: 1.989,42.454; p = 0.004). CST6 promoter methylation status in tumor cells seems to provide important prognostic information in operable breast cancer and merits to be further evaluated and validated in a larger cohort of patients. © 2009 UICC [source] Transglutaminase 3 as a prognostic biomarker in esophageal cancer revealed by proteomicsINTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Norihisa Uemura Abstract To develop a prognostic biomarker for esophageal squamous cell carcinoma (ESCC), we examined the proteomic profile of ESCC using two-dimensional difference gel electrophoresis (2D-DIGE), and identified proteins associated with prognosis by mass spectrometry. The prognostic performance of the identified proteins was examined by immunohistochemistry in additional cases. We identified 22 protein spots whose intensity was statistically different between ESCC cases with good (N = 9; survived more than 5 years without evidence of recurrence) and poor (N = 24; died within 2 years postsurgery) prognosis, within the patient group that had two or more lymph node metastases. Mass spectrometric protein identification resulted in 18 distinct gene products from the 22 protein spots. Transglutaminase 3 (TGM3) was inversely correlated with shorter patient survival. The prognostic performance of TGM3 was further examined by immunohistochemistry in 76 ESCC cases. The 5-year disease-specific survival rate was 64.5% and 32.1% for patients with TGM3-positive and TGM3-negative tumors, respectively (p = 0.0033). Univariate and multivariate analyses revealed that TGM3 expression was an independent prognostic factor among the clinicopathologic variables examined. It is noteworthy that the prognostic value of TGM3 was shown to be higher than those of the lymph node metastasis, intramural metastasis and vascular invasion status. These results establish TGM3 as a novel prognostic biomarker for ESCC for the first time. Examination of TGM3 expression may provide novel therapeutic strategies to prevent recurrence of ESCC. © 2008 Wiley-Liss, Inc. [source] Putative functional polymorphisms of MMP9 predict survival of NSCLC in a Chinese populationINTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Guangfu Jin Abstract Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and their over-expression is often associated with unfavorable survival of non-small cell lung cancer (NSCLC). Because genetic variants can alter expression level or biological activity of MMPs, we hypothesized that potentially functional single nucleotide polymorphisms (SNPs) in key MMP genes may be associated with the survival of NSCLC patients. We selected and genotyped 14 putative functional SNPs in six MMP genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) using PCR-RFLP methods in 561 NSCLC patients. Kaplan-Meier method with the log-rank test and Cox proportional hazard models were used for the survival analyses. The C-1562T, Arg279Gln and Arg668Gln polymorphisms in MMP9 were significantly associated with survival of patients with NSCLC (log-rank p values = 0.032, 0.038 and 0.036, respectively). The C-1562T and Arg668Gln loci were in complete linkage disequilibrium (r2 = 1). Patients carrying the 668Gln allele had improved survival with a median survival time (MST) of 51.6 months, compared with 21.8 months for those with the 668Arg/Arg genotype (log-rank p = 0.010). In contrast, the 279Gln/Gln genotype was associated with a significantly shortened MST (17.3 months, log-rank p = 0.030) in the recessive model. In the final multivariate Cox regression model, 279Gln/Gln was identified as an independent prognostic factor with an adjusted hazard ratio of 1.60 (95% confidence interval 1.07,2.41). The MMP9 Arg279Gln and Arg668Gln SNPs are potential predictors of survival in NSCLC patients. © 2008 Wiley-Liss, Inc. [source] Reduction of TIP30 correlates with poor prognosis of gastric cancer patients and its restoration drastically inhibits tumor growth and metastasisINTERNATIONAL JOURNAL OF CANCER, Issue 3 2009Xiaohua Li Abstract Gastric cancer is an aggressive cancer with poor prognosis. Identification of precise prognostic marker and effective therapeutic target is important in the treatment of gastric cancer. TIP30, a newly identified tumor suppressor, appears to be involved in multiple functions including tumorigenic suppression, apoptosis induction and diminishing angiogenic properties. Here, the level of TIP30 expression was determined in gastric cancer, and the impact of its alteration on cancer biology and clinical outcome was investigated. We found that TIP30 protein was absent or reduced in gastric cancer cell lines. There was also a loss or substantial decrease of TIP30 expression in 106 cases of gastric tumors as compared with that in normal gastric mucosa (p < 0.05), which was significantly associated with inferior survival duration. In a Cox proportional hazards model, TIP30 expression independently predicted better survival (p < 0.05). We also restored TIP30 protein expression in human gastric cancer-derived cells AGS and MKN28 lacking endogenous TIP30 protein to study the effects of TIP30 expression on cell proliferation, cell kinetics, tumorigenicity and metastasis in BALB/c nude mice and found that adenoviral-mediated restoration of TIP30 expression led to downregulation of cyclin D1, Bcl-2, Bcl-xl, but to upregulation of p27, Bax, p53, caspase 3 and 9 expression, cell cycle G0/G1 arrest and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Taken together, the present work revealed a novel function of TIP30, which can possibly be used as an independent prognostic factor and a potential therapeutic target for gastric cancer. © 2008 Wiley-Liss, Inc. [source] Prognostic evaluation of epidermal fatty acid-binding protein and calcyphosine, two proteins implicated in endometrial cancer using a proteomic approachINTERNATIONAL JOURNAL OF CANCER, Issue 10 2008Zhengyu Li Abstract With the aim to translate the discovery from proteomic research into clinical applications, we identified epidermal fatty acid-binding protein (E-FABP) and calcyphosine (CAPS) by MALDI-Q-TOF MS and validated their overexpressions by immunoblotting. Their expression statuses were examined by immunohistochemistry in 39 normal endometrium, 29 endometrial intraepithelial neoplasia (EIN) and 84 endometrial cancer (EC) cases. We evaluated the correlations to the clinicopathologic characteristics and determined whether these proteins had prognostic significance. Expressions of E-FABP and CAPS were increased 2.64- and 2.18-fold in EC by immunoblotting. Immunoreactivity of both E-FABP and CAPS were stronger in EC than in EIN or normal tissues (p < 0.001 and < 0.001). Stronger immunoreactivity of E-FABP and CAPS were shown to present with poor differentiation (p = 0.032 and 0.001), but no relevance was observed with staging (p = 1.368 and 4.306). Survival analysis indicated that immunoreactivity of CAPS was correlated to poor survival (p = 0.018), but E-FABP status appeared to be no correlation to the clinical outcome of patients (p = 0.865). Multivariate analysis indicated that CAPS might be an independent prognostic factor for survival in patients with EC (p = 0.008). Results demonstrated the ubiquitous overexpressions of E-FABP and CAPS in EC and the correlations to the clinicopathologic parameters. CAPS might be a potential prognostic factor for survival in patients with EC. The research pattern from proteomics to clinical specimens would have widespread applications. © 2008 Wiley-Liss, Inc. [source] Social class is an important and independent prognostic factor of breast cancer mortalityINTERNATIONAL JOURNAL OF CANCER, Issue 5 2006Christine Bouchardy Abstract 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. © 2006 Wiley-Liss, Inc. [source] Interleukin-10 expression significantly correlates with minor CD8+ T-cell infiltration and high microvessel density in patients with gastric cancerINTERNATIONAL JOURNAL OF CANCER, Issue 8 2006Teruhisa Sakamoto Abstract We aimed to investigate the relationships between interleukin-10 (IL-10) expression and both the clinicopathological findings and prognoses in patients with gastric cancer and to compare IL-10 expression with microvessel (MV) density and CD8+ T lymphocyte infiltration to evaluate its effects on angiogenesis and immune responses in gastric cancer. IL-10 expression was determined in gastric cancer patients by reverse transcription-polymerase chain reaction (RT-PCR) or immunohistochemical procedures. Two of 7 normal gastric tissues showed IL-10 mRNA expression, while its expressions were confirmed in all advanced gastric carcinoma tissues examined (n = 11) by RT-PCR. Immunohistochemical staining demonstrated that IL-10 expression was detected in 52 (47.7%) of 109 cases. There was a close correlation between IL-10 expression and MV density. IL-10 expression inversely correlated with CD8+ T-lymphocyte infiltration. The prognoses of patients whose tumors expressed IL-10 were significantly worse than those of patients whose tumors did not express IL-10. Multivariate analysis indicated IL-10 expression was an independent prognostic factor. IL-10 might be associated with tumor progression by stimulating angiogenesis and suppressing immune responses in gastric cancer. © 2005 Wiley-Liss, Inc. [source] Epidermal growth factor receptor mutations in needle biopsy/aspiration samples predict response to gefitinib therapy and survival of patients with advanced nonsmall cell lung cancerINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Jin-Yuan Shih Abstract Recently, mutations in the epidermal growth factor receptor (EGFR) gene in nonsmall cell lung cancer (NSCLC) patients were reported to correlate with gefitinib response. Less than 30% of NSCLC patients are surgically resectable; however, molecular analysis has to rely on nonsurgical diagnostic tissue samples. The objective of this study is to investigate EGFR mutation analysis on needle biopsy/aspiration samples and its correlations with gefitinib response and patients' survival. EGFR mutation was assessed from DNA of 63 paraffin-embedded small needle biopsy/aspiration specimens from 62 patients with NSCLC treated with gefitinib. The peripheral blood lymphocyte DNA of the patients was sequenced to verify the EGFR mutation. EGFR mutations were found in 47% of 62 patients (60% of 20 CT-guided biopsies, 44% of 18 ultrasound-guided biopsies, 31% of 16 endoscopic biopsies and 44% of 9 effusion cell blocks). EGFR mutations were frequently present in females (p = 0.006) and never smokers (p = 0.04). Patients with EGFR mutations had a significantly better response rate compared to that of the nonmutation group (p < 0.001). Multivariate analysis showed that EGFR mutation (p < 0.001) and PS 0,1 (p = 0.02) were independently associated with a better response rate. Cox regression analysis showed that EGFR mutation was the independent prognostic factor for progression-free survival (p = 0.008) and overall survival (p = 0.03). In conclusion, EGFR mutation analysis is feasible in needle biopsy/aspiration paraffin-fixed specimens. EGFR mutation is an independent predictor of gefitinib response and survival in patients of advanced NSCLC treated by gefitinib. © 2005 Wiley-Liss, Inc. [source] GRP78 expression correlates with histologic differentiation and favorable prognosis in neuroblastic tumorsINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Wen-Ming Hsu Abstract Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum protein, is essential for the differentiation of neuroblastoma cells and is selectively induced when the cells are undergoing apoptosis. These findings suggest that GRP78 may affect the tumor behavior of neuroblastoma. Our study evaluates the association of clinicopathologic factors and patient survival with the expression of GRP78 in patients with neuroblastoma. GRP78 expression in 68 neuroblastic tumors was investigated semiquantitatively by immunohistochemistry. GRP78 mRNA and protein levels in 7 tumor tissues were also quantified by real-time PCR and Western blot respectively and correlated well with the immunohistochemical results. Forty (58.8%) of the 68 neuroblastic tumors showed positive GRP78 expression. The percentage of positive GRP78 immunostaining increased as the tumor histology became differentiated (p = 0.001). Furthermore, positive GRP78 expression strongly correlated with early clinical stages (P = 0.002) but inversely correlated with MYCN amplification (p = 0.001). Kaplan-Meier analysis showed that patients with positive GRP78 expression did have better survival than those with negative expression (5-year survival rate, 72.9% and 23.4% respectively, p < 0.001). Multivariate analysis further showed that GRP78 expression was an independent prognostic factor. Moreover, GRP78 expression predicted better survival in patients with either undifferentiated or differentiated histologies. GRP78 expression still had significant prognostic value when the analysis was restricted to tumors of advanced stages or without MYCN amplification. Thus, GRP78 can serve as a novel independent favorable prognostic factor for patients with neuroblastoma. © 2004 Wiley-Liss, Inc. [source] Prognostic relevance of TGF-,1 and PAI-1 in cervical cancerINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Suzanne Hazelbag Abstract Cervical carcinoma is a human papilloma virus (HPV)-related immunogenic type of malignancy, in which escape of the tumor from the hosts' immune response is thought to play an important role in carcinogenesis. The multifunctional cytokine transforming growth factor-,1 (TGF-,1) is involved in immunosuppression, stroma and extracellular matrix formation and controlling (epithelial) cell growth. The plasminogen activating (PA) system plays a key role in the cascade of tumor-associated proteolysis leading to extracellular matrix degradation and stromal invasion. Changes in expression of components of this system, including plasminogen activator inhibitor-1 (PAI-1), have been associated with poor prognosis in a variety of solid tumors. The present study was undertaken to assess the role of both components on relapse, survival and other clinicopathologic parameters in cervical cancer. The expression of TGF-,1 mRNA in 108 paraffin-embedded cervical carcinomas was detected by mRNA in situ hybridization. Immunohistochemistry was used to investigate the expression of PAI-1 protein. The presence of cytoplasmatic TGF-,1 mRNA in tumor cells was not significantly correlated with the other clinicopathologic parameters investigated or with a worse (disease-free) survival. Expression of the PAI-1 protein in tumor cells was strongly correlated with worse overall and disease-free survival, in addition to well-known prognostic parameters such as lymph node metastasis, depth of tumor infiltration, tumor size and vasoinvasion. In the multivariate analysis, PAI-1 turned out to be a strong independent prognostic factor. In a subgroup of patients without lymph node metastases, PAI-1 was predictive for worse survival and relapse of disease, too. Our results show that the (enhanced) expression of PAI-1 by carcinoma cells is correlated with worse (overall and disease-free) survival of patients with cancer of the uterine cervix. The expression of TGF-,1 in itself is not associated with worse survival in these patients. Although simultaneous presence of the 2 factors was observed in all tumors, induction of PAI-1 by TGF-,1 could not be demonstrated in our group of cervical carcinomas. © 2004 Wiley-Liss, Inc. [source] Proliferative activity of plasma cells is the most relevant prognostic factor in elderly multiple myeloma patientsINTERNATIONAL JOURNAL OF CANCER, Issue 5 2004R. García-Sanz Abstract Although multiple myeloma (MM) is predominantly a disease of the elderly, few studies have focused on the identification of prognostic factors in this group of patients. Four hundred twenty five MM patients >65 years were uniformly treated with chemotherapy (MP or VCMP/VBAD). Multivariate analysis identified 4 factors with independent unfavorable prognostic influence: high percentage of S-phase bone marrow plasma cells (>2.5%); elevated ,2 microglobulin (B2M) (>4 mg/L); age >80 years old; and LDH serum levels (above normal limit). The S-phase value was the most powerful independent prognostic factor to discriminate subgroups of patients with different prognosis. Thus, 3 main risk categories could be identified according to S-phase values: ,1%, 1,3% and >3%, with median survivals of 34, 22 and 12 months, respectively (p < 0.0001). Our study also proved the value for elderly patients of the recently developed International Score System (ISS) based on B2M and albumin. Furthermore, the number of S-phase cells helped to subdivide the ISS III Group identifying a subset of patients with very poor prognosis defined by an additional high S-phase, who displayed a median survival of only 8 months. These results demonstrate that elderly patients can be accurately classified according to prognosis, which may be particularly valuable when comparing the efficacy of new treatment strategies. Moreover, our results underline the high prognostic value of proliferative activity of PC, a parameter that should be considered in routine laboratory investigations of MM. © 2004 Wiley-Liss, Inc. [source] Downregulation of KiSS-1 expression is responsible for tumor invasion and worse prognosis in gastric carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 6 2004Dipok Kumar Dhar Abstract KiSS-1 is a promising candidate tumor-suppressor gene and may play a key role in the metastatic cascade. The expression profile and the role of KiSS-1 in cancer progression are largely unknown in most of the cancers, including gastric cancer. In this study, KiSS-1 expression was evaluated by RNase protection assay and localization was done by in situ hybridization in 40 gastric cancers and their adjacent normal gastric mucosa. For comparison with clinicopathologic characteristics and patient prognosis, all patients were divided into 2 groups having high and low KiSS-1 expression by using the median as the cutoff value of KiSS-1 expression as determined by the RNase protection assay. Gastric cancers with low KiSS-1 had frequent venous invasion, distant metastasis and tumor recurrence. Accordingly, patients with low KiSS-1 -expressing tumors had a significantly worse overall and disease-free survival. In multivariate analysis, KiSS-1 became the strongest independent prognostic factor among the conventional prognosticators for gastric cancer patients. Collectively, these findings suggest that KiSS-1 may play a crucial role in gastric cancer invasion and could be a useful target for therapeutic intervention. © 2004 Wiley-Liss, Inc. [source] Vitamin D receptor gene polymorphisms are associated with increased risk and progression of renal cell carcinoma in a Japanese populationINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2007Wataru Obara Aim: Biological and epidemiologic data suggest that 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) levels may influence development of renal cell carcinoma. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of 1,25(OH)2D3 and additionally interacts with other cell signaling pathways that influence cancer progression. VDR gene polymorphisms may play an important role in risk of incidence for various malignant tumors. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of renal cell carcinoma (RCC) in a Japanese population. Methods: To analyze risk of RCC depending on VDR polymorphism, a case,control association study was performed. The VDR gene polymorphisms at three locations, BsmI, ApaI and TaqI, were genotyped in 135 RCC patients and 150 controls in a Japanese population. Logistic regression models were used to assess the genetic effects on prognosis. Results: Significant differences in the ApaI genotype were observed between RCC patients and controls (,2 = 6.90, P = 0.032). No statistical significant difference was found in the BsmI and TaqI polymorphisms. The frequency of the AA genotype in the ApaI polymorphism was significantly higher in the RCC patients than in the controls (odds ratio, 2.59; 95% confidence intervals, 1.21,5.55; P = 0.012). Multivariate regression analysis showed that the AA genotype was an independent prognostic factor for cause-specific survival (relative risk 3.3; P = 0.038). Conclusion: The AA genotype at the ApaI site of the VDR gene may be a risk of incidence and poor prognosis factor for RCC in the Japanese population. Additional studies with a large sample size and investigation of the functional significance of the ApaI polymorphism in RCC cells are warranted. [source] Inverse correlation of microvessel density with metastasis and prognosis in renal cell carcinomaINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2004TETSUYA IMAO Abstract Background: Although a correlation between microvessel density (MVD) and tumor aggressiveness has been established for several malignancies, the data for renal cell carcinoma (RCC) is conflicting. In order to clarify the significance of MVD, we investigated the relationships between MVD and tumor stage, grade, size, occurrence of metastasis and patient survival. Methods: Tumor specimens from 70 patients with primary renal cell carcinoma were examined by immunohistochemical staining for CD34. Results: There was a tendency for MVD to decrease from G1 to G3 tumors or from stage T1 to T3 tumors, although this was not statistically significant. However, the MVD for 56 non-metastatic and 14 metastatic tumors were significantly different (P = 0.005) at 109 ± 67 and 58 ± 35 per ×400 field (mean ± SD), respectively. Microvessel density for 36 large and 34 small tumors was also significantly different (P < 0.0001) at 48 ± 22 and 142 ± 54 per ×400 field, respectively. The survival rate of patients with small, low grade and hypervascular tumors was significantly higher than that of patients with large (P = 0.0015), high grade (P = 0.05) or low MVD (P = 0.039) tumors. Cox proportional hazards regression analysis showed that tumor grade and size emerged as independent prognostic factors. Conclusion: High MVD in RCC was inversely associated with tumor aggressiveness, but MVD was not the independent prognostic factor. [source] Microscopic venous invasion in renal cell carcinoma as a predictor of recurrence after radical surgeryINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2004TAKESHI ISHIMURA Abstract Background: The objective of the present study was to investigate the significance of microscopic venous invasion (MVI) as a prognostic factor for patients with renal cell carcinoma (RCC) who underwent radical surgery. Methods: The study included a total of 157 consecutive patients with non-metastatic RCC who underwent radical surgery between January 1986 and December 2002. The median follow-up period was 45 months (range 6,162 months). Microscopic venous invasion was defined by the presence of a cancer cell in blood vessels based on the examination of hematoxylin-eosin stained specimens. Other prognostic variables were assessed by multivariate analysis to determine whether there was a significant impact on cancer-specific and recurrence-free survivals. Results: Microscopic venous invasion was found in 70 patients, and of this number, 17 (24.7%) developed a tumor recurrence and 12 (17.1%) died of cancer progression, while only six (6.9%) of the remaining 87 patients without MVI presented with disease-recurrence and three (3.5%) died of cancer. Among the factors examined, the presence of MVI was significantly associated with age, mode of detection, tumor size, pathological stage and tumor grade; however, only pathological stage was an independent predictor for disease-recurrence, and none of these factors were available to predict cancer-specific survival in multivariate analyses. In 120 patients with pT1 or pT2 disease, MVI was noted in 36 patients. In this subgroup, recurrence-free survival rates in patients with MVI were significantly lower than those in patients without MVI, and MVI was the only independent prognostic predictor for disease-recurrence in a multivariate analysis. Conclusion: Microscopic venous invasion is not an independent prognostic factor in patients with non-metastatic RCC who underwent radical surgery; however, it could be the only independent predictor of disease-recurrence after radical surgery for patients with pT1 or pT2 disease. [source] p27Kip1 as a prognostic factor in breast cancer: a systematic review and meta-analysisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2010Xiaoxiang Guan Abstract The aim of this study was to comprehensively evaluate via a meta-analysis the association between p27 expression and clinical outcome in breast cancer patients. We conducted a meta-analysis of 20 studies (n= 6463 patients) that evaluated the correlation between p27 expression and indicators of breast cancer clinical outcome, including overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS). Data pooling was performed by RevMan 4.2. A total of 60% (9 of 15) of the studies showed a significant association between p27 high expression and OS, whereas 25% (2 of 8) and 60% (3 of 5) studies demonstrated a correlation between p27 high expression and DFS and RFS, respectively. The relative risks (RRs) were 1.34 (1.26,1.42) for OS (P < 0.00001), 1.27 (1.10,1.47) for DFS (P= 0.001) and 1.49 (0.92,2.42) for RFS (P= 0.10). In lymph node-negative breast cancer patients, the RRs for OS and RFS were 1.84 (1.30,2.59; P= 0.0005) and 1.30 (0.20,8.50; P= 0.78), respectively. In lymph node-positive breast cancer patients, the RRs for OS and RFS were 2.99 (1.77,5.07; P < 0.0001) and 1.49 (0.80,2.77; P= 0.21), respectively. This meta-analysis indicates that reduced p27 is an independent prognostic factor for poor overall and disease-free cancer survival. [source] | ||||||||||||||||||||||||||||||||||