T. Terada et al., IMMUNOHISTOCHEMICAL DEMONSTRATION OF MET OVEREXPRESSION IN HUMAN INTRAHEPATIC CHOLANGIOCARCINOMA AND IN HEPATOLITHIASIS, Human pathology, 29(2), 1998, pp. 175-180
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.