Open Access Open Badges Research article

High expression of BCL-2 predicts favorable outcome in non-small cell lung cancer patients with non squamous histology

Valsamo K Anagnostou1*, Frank J Lowery1, Vassiliki Zolota2, Vassiliki Tzelepi2, Arun Gopinath1, Camil Liceaga1, Nikolaos Panagopoulos3, Konstantina Frangia4, Lynn Tanoue5, Daniel Boffa6, Scott Gettinger7, Frank Detterbeck6, Robert J Homer1, Dimitrios Dougenis3, David L Rimm1 and Konstantinos N Syrigos7

Author Affiliations

1 Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

2 Department of Pathology, University of Patras, Patras, Greece

3 Cardiothoracic Surgery Department, University of Patras, Patras, Greece

4 Department of Pathology, Sotiria General Hospital, Athens, Greece

5 Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT, USA

6 Department of Surgery, Yale University School of Medicine, New Haven, CT, USA

7 Section of Medical Oncology, Department of Internal Medicine, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA

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BMC Cancer 2010, 10:186  doi:10.1186/1471-2407-10-186

Published: 9 May 2010



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.


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.


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).


Bcl-2 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of NSCLC patients.