TY - JOUR
T1 - High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology
AU - Anagnostou, Valsamo K.
AU - Lowery, Frank J.
AU - Zolota, Vassiliki
AU - Tzelepi, Vassiliki
AU - Gopinath, Arun
AU - Liceaga, Camil
AU - Panagopoulos, Nikolaos
AU - Frangia, Konstantina
AU - Tanoue, Lynn
AU - Boffa, Daniel
AU - Gettinger, Scott
AU - Detterbeck, Frank
AU - Homer, Robert J.
AU - Dougenis, Dimitrios
AU - Rimm, David L.
AU - Syrigos, Konstantinos N.
N1 - Funding Information:
We thank Dr Dina Tiniakos (Laboratory of Histology and Embryology, Medical School, University of Athens) for her assistance on obtaining the tissue specimens from University of Patras, Greece, Dr Ioannis Tourkantonis (Sotiria General Hospital) for updating the Greek clinical database at Sotiria General Hospital and Dr Michael Peyton (UT Southwestern Medical Center, Dallas, TX) for donation of NSCLC cell lines. This study was supported by a grant from the Thoracic Oncology Group, Yale University School of Medicine, New Haven, CT.
PY - 2010/5/9
Y1 - 2010/5/9
N2 - 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®, 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.
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®, 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.
UR - http://www.scopus.com/inward/record.url?scp=77951941324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77951941324&partnerID=8YFLogxK
U2 - 10.1186/1471-2407-10-186
DO - 10.1186/1471-2407-10-186
M3 - Article
C2 - 20459695
AN - SCOPUS:77951941324
SN - 1471-2407
VL - 10
JO - BMC cancer
JF - BMC cancer
M1 - 186
ER -