PMID- 20459695 OWN - NLM STAT- MEDLINE DCOM- 20100816 LR - 20211020 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 10 DP - 2010 May 9 TI - High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology. PG - 186 LID - 10.1186/1471-2407-10-186 [doi] AB - BACKGROUND: Bcl-2 promotes cell survival by inhibiting adapters needed for the activation and cleavage of caspases thus blocking the proteolytic cascade that ultimately dismantles the cell. Bcl-2 has been investigated as a prognostic factor in non small cell lung cancer (NSCLC) patients with conflicting results. METHODS: Here, we quantitatively assessed Bcl-2 expression in two large and independent cohorts to investigate the impact of Bcl-2 on survival. AQUA(R), a fluorescent-based method for analysis of in situ protein expression, was used to measure Bcl-2 protein levels and classify tumors by Bcl-2 expression in a cohort of 180 NSCLC patients. An independent cohort of 354 NSCLC patients was used to validate Bcl-2 classification and evaluate outcome. RESULTS: Fifty % and 52% of the cases were classified as high expressers in training and validation cohorts respectively. Squamous cell carcinomas were more likely to be high expressers compared to adenocarcinomas (63% vs. 45%, p = 0.002); Bcl-2 was not associated with other clinical or pathological characteristics. Survival analysis showed that patients with high BCL-2 expression had a longer median survival compared to low expressers (22 vs. 17.5 months, log rank p = 0.014) especially in the subset of non-squamous tumors (25 vs. 13.8 months, log rank p = 0.04). Multivariate analysis revealed an independent lower risk for all patients with Bcl-2 expressing tumors (HR = 0.53, 95% CI 0.37-0.75, p = 0.0003) and for patients with non-squamous tumors (HR = 0.5, 95% CI 0.31-0.81, p = 0.005). CONCLUSIONS: Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients. FAU - Anagnostou, Valsamo K AU - Anagnostou VK AD - Department of Pathology, Yale University School of Medicine, New Haven, CT, USA. valsamo.anagnostou@yale.edu FAU - Lowery, Frank J AU - Lowery FJ FAU - Zolota, Vassiliki AU - Zolota V FAU - Tzelepi, Vassiliki AU - Tzelepi V FAU - Gopinath, Arun AU - Gopinath A FAU - Liceaga, Camil AU - Liceaga C FAU - Panagopoulos, Nikolaos AU - Panagopoulos N FAU - Frangia, Konstantina AU - Frangia K FAU - Tanoue, Lynn AU - Tanoue L FAU - Boffa, Daniel AU - Boffa D FAU - Gettinger, Scott AU - Gettinger S FAU - Detterbeck, Frank AU - Detterbeck F FAU - Homer, Robert J AU - Homer RJ FAU - Dougenis, Dimitrios AU - Dougenis D FAU - Rimm, David L AU - Rimm DL FAU - Syrigos, Konstantinos N AU - Syrigos KN LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20100509 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - 0 (Biomarkers, Tumor) RN - 0 (Proto-Oncogene Proteins c-bcl-2) SB - IM MH - Adenocarcinoma/*chemistry/mortality/pathology/therapy MH - Aged MH - Biomarkers, Tumor/*analysis MH - Carcinoma, Large Cell/*chemistry/mortality/pathology/therapy MH - Carcinoma, Non-Small-Cell Lung/*chemistry/mortality/pathology/therapy MH - Carcinoma, Squamous Cell/*chemistry/mortality/pathology/therapy MH - Cell Differentiation MH - Cohort Studies MH - Connecticut MH - Female MH - Greece MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*chemistry/mortality/pathology/therapy MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Predictive Value of Tests MH - Proportional Hazards Models MH - Proto-Oncogene Proteins c-bcl-2/*analysis MH - Reproducibility of Results MH - Retrospective Studies MH - Risk Assessment MH - Risk Factors MH - Time Factors MH - Treatment Outcome MH - Up-Regulation PMC - PMC2875218 EDAT- 2010/05/13 06:00 MHDA- 2010/08/17 06:00 PMCR- 2010/05/09 CRDT- 2010/05/13 06:00 PHST- 2009/08/24 00:00 [received] PHST- 2010/05/09 00:00 [accepted] PHST- 2010/05/13 06:00 [entrez] PHST- 2010/05/13 06:00 [pubmed] PHST- 2010/08/17 06:00 [medline] PHST- 2010/05/09 00:00 [pmc-release] AID - 1471-2407-10-186 [pii] AID - 10.1186/1471-2407-10-186 [doi] PST - epublish SO - BMC Cancer. 2010 May 9;10:186. doi: 10.1186/1471-2407-10-186.