Altered mucin gene expression in stone-containing intrahepatic bile ducts and cholangiocarcinomas

Neoplastic transformation of epithelial cells is commonly associated with a lterations in the synthesis and structures of mucin. Mucin protein epitopes and mRNA levels were frequently altered in adenocarcinomas compared to cor responding normal tissues. Clinically, hepatolithiasis has been regarded as a risk factor for cholangiocarcinoma. The aims of this study were to deter mine the possible alteration of mucin gene expression in stone-containing i ntrahepatic bile ducts and cholangiocarcinomas and to try to predict whethe r or not hepatolithiasis has a predisposition to development of cholangioca rcinoma. In situ hybridization with DIG-tailed oligonucleotides was perform ed on sections of paraffin-embedded tissues of stone-containing intrahepati c bile ducts, cholangiocarcinomas, and normal controls to identify the expr ession of MUC2, MUC3, MUC4, MUC5B, and MUC5AC in nonneoplastic and neoplast ic biliary epithelium. The findings showed that (1) while multiple diverse mucin genes were expressed in the biliary epithelium, MUC3 and MUC5B mRNA w ere the main mucin genes expressed in the biliary epithelium of stone-conta ining intrahepatic bile ducts and normal controls; (2) absent or decreased expression of MUC2. MUC3, and MUC5B of mRNA was found in cholangiocarcinoma s in contrast to nonneoplastic biliary epithelium; and (3) increased expres sion of MUC4 and MU5AC of mRNA was found in cholangiocarcinomas and the bil iary epithelium, especially for dysplastic cells of stone-containing intrah epatic bile ducts compared with normal controls. In this study, using in si tu hybridization we demonstrated that neoplastic transformation of the bili ary epithelium is accompained by alterations in mucin gene expression, the altered mucin gene expression in dysplastic cells of stone-containing intra hepatic bile ducts may reflect a higher potential for malignant transformat ion in these cells, and it could be a precursor of cholangiocarcinoma in th e presence of hepatolithiasis.