Tumor laterality influences the prognostic impact of Bcl-2 expression in curatively resected NSCLC patients

Introduction: Overexpression of anti-apoptotic proteins shows impact on prognosis in in non-small-cell lung cancer (NSCLC). To investigate the effects in NSCLC, we focused on several apoptotic factors such as Bcl-2, Bcl-xl, Mcl-1, and pp32/PHAPI and included the aspect of tumor laterality, since lung tumor laterality also influences surgical procedures and mortality. Material and Methods: Using tissue microarray Immunohistochemistry, the prognostic impact of the expression profiles of Bcl-2, Bcl-xl, Mcl-1 and pp32/PHAPI was investigated in 436 NSCLC tissue samples (median age: 65 years; 77% male) with correlation analysis, Log rank tests and Cox proportional hazard models. Results: For Bcl-2, positive expression was found in 97 cases (23%), for Bcl-xl in 151 cases (37%), for Mcl-1 in 230 cases (57%) and for in 279 cases (66%). Both univariate and multivariate analysis identified the expression of Bcl-2 as the best prognostic marker. In stage I non-squamous cell tumors, a synergistic positive prognostic effect of Bcl-2 and Bcl-xl co-expression was found. Moreover, Bcl-2 expression of tumors located on the right side showed best prognostic impact (p=0.001). Conclusion: We identified Bcl-2 to be a strong independent factor for an improved outcome in resected NSCLC patients, at first glance contradictory to the findings in lymphomas and other solid tumors. However, we hypothesize this effect to directly derive from a better accessibility and resectability of invisibly affected distant lymph nodes in right sided surgical procedures in Bcl2 positive tumors. Future concepts in surgical oncology should owe respect to laterality.