Expression of the c‐met protooncogene in human hepatocellular carcinoma

Abstract

The c‐met protooncogene is a growth factor receptor with tyrosine kinase activity. Recently the hepatocyte growth factor was identified as the ligand for this receptor. Because the hepatocyte growth factor is a most potent mitogen in hepatocytes, possible involvement of c‐met expression in hepatocarcin genesis is suspected. In this study, we examined c‐met expression in 23 hepatocellular carcinoma cases by means of Northern‐blot analysis and an immunohistochemical study. Northern‐blot analysis revealed c‐met mRNA expression in the tumors of 6 of 19 patients (31.6%); in the immunohistochemical study, c‐met protein was detected in 16 of 23 patients (69.6%). With both methods, c‐met was found to be overexpressed in hepatocellular carcinoma compared with the surrounding normal liver. Comprehensive analysis showed that c‐met protein expression was correlated with poor‐to‐moderate differentiation of cancer cells (p < 0.05). Tumor proliferative activity of hepatocellular carcinoma was evaluated by means of Ki‐67 labeling index. All cases with increased tumor proliferative activity showed c‐met protein expression, although the elevation of proliferative activity in the c‐met–positive group was not statistically significant. These data suggest that the overexpression of c‐met plays an important role in the development of hepatocellular carcinoma. (Hepatology 1994;20:1231–1236). Copyright © 1994 American Association for the Study of Liver Diseases