The potential role of bcl-2 mRNA and protein exression in hepatocellular carcinomas

BACKGROUND: The bcl-2 gene regulates programmed cell death by providing a survival advantage to rapidly proliferating cells. In several malignant tumors bcl-2 presence has been associated with favorable prognosis. In the liver, bcl-2 is expressed in bile ductular cells and tumors of biliary origin. This study investigates the expression of bcl-2 mRNA and protein in hepatocellular carcinomas (HCC). MATERIALS AND METHODS: The study comprised 35 primary HCC resected from 35 patients; 21 males and 14 females, aged from 43-59 years. The tumors were graded according to Edmondson criteria. In 28 cases HCC was developed on the background of cirrhotic liver. In 9 instances the patients received chemoembolization before surgery. The presence of bcl-2 mRNA was assessed on paraffin-embedded, 4 microm-thick sections, using a standard in situ hybridization method with a commercially available bcl-2 probe (Maxim Biotech, USA), while the streptavidin-biotin immunohistochemical technique was employed to detect bcl-2 protein expression using the monoclonal anti-bcl-2 antibody (DAKO, USA). The results were expressed as % of tumor-positive cells following morphometric analysis. RESULTS: The in situ hybridization study revealed bcl-2 mRNA expression in 25 out of 35 (70%) HCC. In addition, bcl-2 mRNA was detected in hyperplastic cholangioles within fibrous septae in the periphery of the tumors. Immunohistochemical staining failed to reveal any bcl-2 protein expression in tumor cells of HCC, whereas hyperplastic cholangioles of the fibrous septae, in the periphery of the tumors and intratumoral lymphocytes displayed a strong-positive cytoplasmic (perinuclear) stain. No significant correlations were recorded between bcl-2 mRNA expression and tumor histological pattern, grade, stage and the use of previous chemoembolization. CONCLUSION: In hepatocellular carcinomas, the bcl-2 gene is frequently present but its protein product is absent. This suggests a post-translational mechanism of bcl-2 protein degradation, indicating that bcl-2 does not play a substantial role in the progress of hepatocellular carcinoma.