OVEREXPRESSION OF C-MET PROTOONCOGENE PRODUCT AND RAISED KI67 INDEX IN HEPATOCELLULAR CARCINOMAS WITH RESPECT TO BENIGN LIVER CONDITIONS

The c-met protooncogene encodes a 190-kd transmembrane tyrosine kinase . This molecule is the receptor for the hepatocyte growth factor (HGF) , which is an important mitogen for hepatocytes both in vitro and in v ivo. in experimental models, the c-met transcripts appeared strongly e xpressed by actively proliferating oval cells (OCs), We evaluated the phenotypic modulation of the c-met protooncogene product (c-met pp), i n 10 hepatocellular carcinomas (HCCs), 5 focal nodular hyperplasias (F NHs), 4 cases of fulminant hepatitis (FH), and 1 regenerated liver, se lected to include the different biological states of hepatocyte (matur e normal hepatocytes, transformed ones, and OCs), The supposed mitogen ic effect of HGF was analyzed by comparing c-met pp overexpression wit h the Ki67 index, whereas anti-OV-6 antibody was used for comparison w ith the presence of OCs. The anti-c-met pp showed a typical plasma mem brane-specific staining in all cases. The signal was much stronger in the HCCs than in the benign conditions. The anti-OV-6 monoclonal antib ody showed positive immunostaining in many of the cells expressing c-m et pp. The percentage of Ki67+ nuclei in high-grade HCCs paralleled c- met protooncogene overexpression. The c-met pp in OV-6+ cells suggests that the paracrine mechanism postulated in experimental models could also apply to human liver.