INCREASED EXPRESSION OF BCL-2 IN DRUG-RESISTANT SQUAMOUS-CELL LUNG CARCINOMAS

The aim of this investigation was to prove whether or not an association exists between Bcl-2 expression and in vitro resistance to doxorubicin in biopsies of 85 human squamous cell lung carcinomas. Additionally, the relationship of Bcl-2 expression with resistance related proteins (P-glycoprotein, glutathione S-transferase-pi, catalase) was analyzed. Of the 85 carcinomas, 17 (20%) revealed Bcl-2 expression by immunohistochemistry. Seventeen of the tumors were classified as sensitive and 68 as resistant by an in vitro predictive test. All 17 Bcl-2-positive carcinomas were resistant to doxorubicin (p=0.018; chi(2)-test). A correlation was found between expression of Bcl-2 and expression of the resistance-related proteins P-glycoprotein and glutathione S-transferase-pi. The median survival time for patients with Bcl-2-negative carcinomas was two years and for Bcl-2-positive tumors over six years (log-rank test; p=0.08). Multivariate analysis (Cox regression model) revealed a borderline significant influence of Bcl-2 (p=0.07), whereas all other clinical factors (age, stage, metastasis) were of no significant influence on survival.