c-erbB-2 protein is expressed in hepatolithiasis and cholangiocarcinoma

T. Terada, K. Ashida, K. Endo, S. Horie, H. Maeta, Y. Matsunaga, K. Takashima, T. Ohta, Y. Kitamura

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)


Aims: The c-erbB-2 proto-oncogene encodes a transmembrane protein which is highly homologous to epidermal growth factor receptor. Overexpression of this c-erbB-2 protein has been reported in many human carcinomas, including breast carcinoma. However, there have been few studies of 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-erbB-2 protein in human cholangiocarcinomas (n = 47), hepatolithiasis (n = 20), fetal livers (n = 36) and normal adult livers (n=6). In normal adult livers and fetal livers, expression of c-erbB-2 protein could not be detected in hepatocytes or intrahepatic biliary cells. In hepatolithiasis, there was overexpression of c-erbB-2 in 15/20 (75%). The expression was found with a membranous pattern on the proliferated intrahepatic bile ducts and proliferated intrahepatic peribiliary glands around the bile ducts containing stones. Hepatocytes were negative for c-erbB-2 protein. Moreover, the biliary cell expression of the c-erbB-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 did not correlate with Ki67 labelling index or p53 expression. Conclusions: These results indicate that aberrant expression of c-erbB-2 protein is found in cholangiocarcinoma and also in noncancerous biliary proliferative lesions such as hepatolithiasis. These findings also suggest that c-erbB-2 oncogene participates not only in cholangio-carcinogenesis but also in biliary cell proliferation in non-neoplastic conditions.

Original languageEnglish
Pages (from-to)325-331
Number of pages7
Issue number4
Publication statusPublished - 1998

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Histology


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