IMMUNOHISTOCHEMICAL DEMONSTRATION OF MET OVEREXPRESSION IN HUMAN INTRAHEPATIC CHOLANGIOCARCINOMA AND IN HEPATOLITHIASIS

Expression of MET, the c-met-encoded receptor for hepatocyte growth fa ctor, has not been investigated in proliferative biliary diseases of h uman liver, including hepatolithiasis and cholangiocarcinoma. Comparat ively, we analyzed by immunohistochemistry the expression of MET in no rmal adult human livers (n = 20), normal postnatal preadult livers (n = 21), fetal livers (n = 36), hepatolithiatic livers (n = 32), and int rahepatic cholangiocarcinomas (n = 26). In normal adult livers, obviou s MET immunoreactivity was not found in any cell types. In fetal liver , MET was weakly expressed in primitive biliary cells (ductal plate an d immature bile ducts) and immature hepatocytes during 8 to 30 gestati onal weeks but was essentially negative thereafter. In hepatolithiasis , a condition of risk for cholangiocarcinoma development, MET was over expressed in proliferated biliary cells in 26 of 32 cases (81%). In th is nonneoplastic proliferative biliary condition, MET immunoreactivity was observed to be most prominent in the hyperplastic septal and larg e bile ducts of liver, and in the proliferated peribiliary glands asso ciated with intrahepatic large bile ducts. In intrahepatic cholangioca rcinoma, MET overexpression in neoplastic biliary epithelium was obser ved in 15 of 26 cases (58%) and correlated with the degree of tumor di fferentiation, being highest in well-differentiated tumors and relativ ely low in poorly differentiated tumors. These data show for the first time that overexpression of MET is a common feature of hyperplastic a nd neoplastic biliary epithelial cells in human liver and suggest that MET/hepatocyte growth factor may be playing an important role in huma n biliary hyperplasia and in cholangiocarcinogenesis in vivo. Copyrigh t (C) 1998 by W.B. Saunders Company.