title: c-erbB-2 protein is expressed in hepatolithiasis and cholangiocarcinoma.
abstract: OBJECTIVE
  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.
  
  
  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 cholangiocarcinogenesis but also in biliary cell proliferation in non-neoplastic conditions.
authors.affiliation: Second Department of Pathology, Tottori University Faculty of Medicine, Yonago Japan.
authors.forename: T
authors.initials: T
authors.lastname: Terada
authors.forename: K
authors.initials: K
authors.lastname: Ashida
authors.forename: K
authors.initials: K
authors.lastname: Endo
authors.forename: S
authors.initials: S
authors.lastname: Horie
authors.forename: H
authors.initials: H
authors.lastname: Maeta
authors.forename: Y
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: K
authors.initials: K
authors.lastname: Takashima
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016158:Genes, p53; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D020347:Lithiasis / Q000378:metabolism*; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
chemical_list: D019394:Ki-67 Antigen; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human