Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bcl-2 gene product inhibits apoptosis and is thought to participate in oncogenesis. Association of bcl-2 immunopositivity with improved prognosis of non-small cell lung cancers (NSCLC) is controversial. Although two studies have reported better survival in bcl-2-immunopositive NSCLCs, a third series has contradicted this finding. The authors studied a relatively larger case series involving 427 patients for whom detailed information on long-term follow-up was available to determine the prognostic significance of bcl-2 expression. The study included 252 adenocarcinomas (AC), 111 squamous cell carcinomas (SCC), and 64 large cell carcinomas (LC). After antigen retrieval, sections were immunostained using a monoclonal anti-bcl-2 antibody (1:60, Clone 124, Dako) and the avidin-biotin complex technique. Staining was scored as positive or negative and also on a semiquantitative scale as 0, low (<10%), moderate (10% to 75%), or extensive (>75%). Bcl-2 immunoreactivity was correlated with survival using the actuarial survival method, Kaplan-Meier method, and log-rank test and was not associated with statistically significant differences in survival for NSCLCs (P = .5537). Differences in survival remained insignificant even after NSCLCs were stratified for cell type, stage, or grade, singly or in combination. Therefore, using this method, bcl-2 immunopositivity does not appear to act as an independent prognostic indicator in NSCLCs.
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PMID:Absence of prognostic significance of bcl-2 immunopositivity in non-small cell lung cancer: analysis of 427 cases. 930 33

Chemoresistance is a major problem in the chemotherapy of non-small cell lung cancers (NSCLCs). Several mechanisms are thought to be involved in drug resistance, including those associated with apoptosis, drug transport and detoxification. Here, we investigated the predictive value of P53, Bcl-2 and lung resistance-related protein (LRP) expression for response to platinum-based chemotherapy, using transbronchial biopsy (TBB) specimens from patients with NSCLC. We evaluated TBB specimens from 57 patients with NSCLC who had not previously been treated with either chemotherapy or radiotherapy before TBB, and who were treated with systemic platinum-based chemotherapy. The specimens included 33 adenocarcinomas, 22 squamous cell carcinomas and two large cell carcinomas. One to 6 courses of chemotherapy were administered. Expression of P53, Bcl-2 and LRP was analyzed by immunohistochemistry using TBB specimens. Positive expression of P53, Bcl-2 and LRP was observed in 28 (49%), 41 (71%) and 42 (73%) of the 57 NSCLCs, respectively. P53 expression correlated significantly with response to chemotherapy in nonsquamous cell carcinomas, including adenocarcinomas and large cell carcinomas (response rates, 38% and 6% for patients with P53-positive and P53-negative tumors, respectively, P = 0.03). LRP expression significantly correlated inversely with response to chemotherapy in squamous cell carcinomas (response rates, 33% and 100% for patients with LRP-positive and LRP-negative tumors, respectively, P = 0.02). Bcl-2 expression did not correlate with response to chemotherapy. These findings indicate that immunostaining for P53 and LRP using TBB specimens may be useful for dividing patients with NSCLC into chemoresponsive and chemoresistant groups.
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PMID:Predictive value of expression of P53, Bcl-2 and lung resistance-related protein for response to chemotherapy in non-small cell lung cancers. 1282 11

This study has investigated a panel of immunomarkers in non-small cell lung carcinoma (NSCLC). Unsupervised hierarchical clustering analysis was used to investigate the possibility of identifying different subgroups in NSCLC based on their molecular expression profile rather than morphological features. A tissue microarray consisting of 284 cases of NSCLC was constructed. Immunohistochemistry was used to detect the presence of 18 biomarkers including synaptophysin, chromogranin, bombesin, NSE, GFI1, ASH-1, p53, p63, p21, p27, E2F-1, cyclin D1, Bcl-2, TTF-1, CEA, HER2/neu, cytokeratin 5/6, and pancytokeratin. Univariate analysis of all 18 markers for prognostic significance was performed. Immunohistochemical scoring data for NSCLC were analysed by unsupervised hierarchical clustering analysis. Kaplan-Meier survival curves were plotted for the different cluster groups of lung tumours identified by this method. Analysis of the three different World Health Organization (WHO) subtypes (adenocarcinoma, squamous cell carcinoma, large cell carcinoma) of NSCLC individually showed that different markers were significant in different subtypes. For example, p53 and p63 were significant for squamous cell carcinoma (p = 0.007 and p = 0.03, respectively), whereas cyclin D1 and HER2/neu were significant prognostic markers for adenocarcinoma (p = 0.025 and p = 0.015, respectively). These markers were not significant prognostic predictors for NSCLC as a group. Hierarchical clustering analysis of NSCLC produced four separate cluster groups, although the vast majority of cases were found in two cluster groups, one dominated by squamous cell carcinoma and the other by adenocarcinoma. The clinical outcomes of cases from the four cluster groups were not significantly different. Prognostic indicators vary between different morphological subtypes of NSCLC. Unsupervised hierarchical clustering analysis, based on an extended immunoprofile, identifies two main cluster groups corresponding to adenocarcinoma and squamous cell carcinoma; cases of large cell carcinomas are assigned to one of these two groups based on their molecular phenotype.
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PMID:Evaluation of immunohistochemical markers in non-small cell lung cancer by unsupervised hierarchical clustering analysis: a tissue microarray study of 284 cases and 18 markers. 1530 43