Expression of bcl-2 protein in non-small cell lung cancer: correlation with clinicopathology and patient survival.

Molecular genetic studies have revealed mutations in a number of oncogenes and tumor suppressor genes in lung cancer. The bcl-2 gene product (bcl-2 protein) is implicated in oncogenesis by its ability to prolong cell death through the inhibition of apoptosis. We investigated expression of bcl-2 in 84 resected human non-small cell lung cancers (NSCLC) and correlated this phenomena with clinicopathology and survival. Immunohistochemical analysis with a monoclonal antibody specific for bcl-2 (Clone 124; Dako) was used to detect the protein in tumor samples. Overall, bcl-2 was detectable in 39 of 84 (46%) NSCLC. The percentage of bcl-2 positive cases varied according to the histological type. Positive bcl-2 immunostaining was observed in 27 of the 46 squamous cell carcinomas (59%), 7 of the 25 adenocarcinomas (28%) and 5 of the 13 large cell carcinomas (38%). The frequency of positive bcl-2 expression in squamous cell carcinomas was significantly higher than that in other histological two types (p = 0.037). Statistical comparisons between the patients' clinical characteristics and bcl-2 status revealed no significant differences in the frequency of bcl-2 expression with respect to sex, T and N factors, as well as TNM stage. The relationship between bcl-2 protein expression and postoperative survival was analyzed in 84 patients. Patients with bcl-2 negative tumors showed significantly shorter survival times than those with bcl-2 positive tumors. In univariate analysis of various potential prognostic factors only TNM stage and bcl-2 test were significant prognostic factors (p < 0.009 and p < 0.008, respectively). In multivariate analysis (Cox proportional hazard model), bcl-2 status (negative test) was independent unfavorable prognostic factor (p = 0.017). In conclusion, this set of observations suggests that assessment of the expression status of bcl-2 by tumors may provide prognostic information on the clinical behavior of NSCLC.