Abnormal expression of MUC1 apomucin and mature MUC1 mucin in biliary epithelial cells in various cystic liver diseases

Abstract

MUC1 apomucin is proposed as an "oncofetal" antigen in the biliary system. We surveyed the biliary expression of MUC1 apomucin and mature MUC1 mucin (highly-glycosylated MUC1 apomucin) in hepatic cysts, biliary microhamartomas, and intrahepatic bile ducts in various cystic liver diseases and clarified the relationship between the expression of these mucins and cystogenesis in the liver. The expression of MUC1 apomucin and mature MUC1 mucin were detected immunohistochemically using the monoclonal antibodies DF3 and SM3, and HMFG1, respectively. We surveyed six livers with adult-type polycystic disease (APCD), six with multiple hepatic cysts without polycystic kidney, 11 with solitary hepatic cysts, and 11 "histologically normal" livers. Biliary microhamartomas were frequently found in the former three. MUC1 apomucin was frequently expressed at the luminar surface of the epithelial cells lining cysts and also in biliary microhamartomas, independent of the type of cystic disease. MUC1 apomucin detected by both monoclonal antibodies (MAbs) DF3 and SM3 was also frequently expressed in the intrahepatic bile ducts from polycystic diseases, particularly the adult-type, whereas such expression was rare in the intrahepatic bile ducts in normal livers. Mature MUC1 mucin was expressed on the luminal surface of the epithelial cells lining cysts in approximately half of hepatic cysts studied, but it was infrequently expressed in biliary microhamartomas and almost absent in the intrahepatic bile ducts. The biliary epithelial cells lining hepatic cysts, biliary microhamartomas, the apparently normal intrahepatic bile ducts in APCD, multiple hepatic cysts, and to a lesser degree, solitary hepatic cysts, express abnormal levels MUC1 apomucin. This implies that biliary epithelial cells expressing MUC1 apomucin are related to the whole cystogenetic process in these diseases. In contrast, the expression of mature MUC1 mucin may be related to the late cystogenetic process in these diseases.