C-ERBB-2 PROTEIN IS EXPRESSED IN HEPATOLITHIASIS AND CHOLANGIOCARCINOMA

Aims: The c-erbB-2 proto-oncogene encodes a transmembrane protein whic h is highly homologous to epidermal growth factor receptor. Overexpres sion of this c-erbB-2 protein has been reported in many human carcinom as, including breast carcinoma. However, there have been few studies o f the expression of c-erbB-2 in cholangiocarcinoma and hepatolithiasis , a condition occasionally associated with cholangiocarcinoma. Methods and results: In this study, we evaluated immunoreactivity for the c-e rbB-2 protein in human cholangiocarcinomas (n = 47), hepatolithiasis ( n = 20), fetal livers (n = 36) and normal adult livers (n = 6), In nor mal adult livers and fetal livers, expression of c-erbB-2 protein coul d not be detected in hepatocytes or intrahepatic biliary cells. In hep atolithiasis, there was overexpression of c-erbB-2 in 15/20 (75%). The expression was found with a membranous pattern on the proliferated in trahepatic bile ducts and proliferated intrahepatic peribiliary glands around the bile ducts containing stones. Hepatocytes were negative fo r c-erbB-2 protein. Moreover, the biliary cell expression of the c-erb B-2 protein correlated significantly with Ki67 labelling index. On the other hand, aberrant expression of c-erbB-2 was found in 33/47 (70%) cholangiocarcinomas. The c-erbB-2 expression in cholangiocarcinomas di d not correlate with Ki67 labelling index or p53 expression. Conclusio ns: These results indicate that aberrant expression of c-erbB-2 protei n is found in cholangiocarcinoma and also in noncancerous biliary prol iferative lesions such as hepatolithiasis. These findings also suggest that c-erbB-2 oncogene participates not only in cholangiocarcinogenes is but also in biliary cell proliferation in non-neoplastic conditions .