Association of Bcl‐2 protein expression with gallbladder carcinoma differentiation and progression and its relation to apoptosis

Abstract

BACKGROUND Bcl-2 protein is believed to play a role in neoplasia by inhibiting tumor cell apoptosis. To assess its contribution to gallbladder tumorigenesis and cancer progression, an immunohistochemical study was performed. METHODS Fifteen adenomas and 68 adenocarcinomas were immunohistochemically and histopathologically investigated for the relation of Bcl-2 expression to p53 status, apoptosis (apoptotic index, AI), and proliferation activity (mitotic index, MI; Ki-67 labeling index, Ki-67 LI). RESULTS The Bcl-2 score, based on intensity and extent, decreased in the order of adenoma, well-differentiated, and moderately to poorly differentiated adenocarcinoma. Early stage carcinomas demonstrated significantly higher Bcl-2 scores than their advanced counterparts (P < 0.05). On the other hand, p53 score, MI, Ki-67 LI, and AI increased in the same order. The Bcl-2 negative adenocarcinomas displayed higher AI and AI-to-MI ratios than the Bcl-2 positive group, especially in the early stage, well-differentiated lesions. A significantly positive correlation between MI(r = 0.549) or Ki-67 LI(r = 0.446) and AI was observed. In early stage carcinomas, adenomatous components in the lesions were found more frequently in the polypoid lesions than in the nonpolypoid lesions (P < 0.05). CONCLUSIONS Expression of Bcl-2 protein in gallbladder tumors appears to be positively associated with tumor cell differentiation and inversely with tumor progression. It may thus play a role in regulating carcinoma growth, especially in the early stage of tumorigenesis. It is believed that the polypoid carcinomas may arise from preexisting adenomas but the nonpolypoid carcinomas may arise as de novo carcinoma. Cancer 1999;85:318–25. © 1999 American Cancer Society.