Clinical impact of c-Met expression and its gene amplification in hepatocellular carcinoma

Abstract

c-Met is an oncogene encoding a receptor for hepatocyte growth factor and, as such, plays a key role in hepatocellular carcinomas (HCC). We evaluated c-Met protein expression and its gene amplification in order to assess whether they were related to tumor recurrence and survival rates among patients who had undergone tumor resection. We used the polymer-based method to perform an immunohistochemistry analysis of c-Met expression on 59 formalin-fixed, paraffin-embedded sections of surgical specimens. c-Met gene amplification was investigated with fluorescence in-situ hybridization. Kaplan-Meier methods and Cox proportional hazards models were used to investigate relationships between c-Met expression, patient characteristics, tumor recurrence, and survival. c-Met expression was associated with portal vein invasion (p=0.006). Recurrence-free survival rates were significantly lower in patients with high levels of c-Met expression (p<0.001). However, c-Met expression levels did not significantly affect overall survival rates (p=0.12). Only 1 patient was found to have c-Met gene amplification; 22 patients were found to have aneuploidy of chromosome 7, on which the c-Met gene is located. Tumors with chromosome 7 polysomy tended to have higher levels of c-Met expression than those with chromosome 7 monosomy or disomy, but this difference was not statistically significant. Although c-Met expression was not significantly associated with c-Met gene amplification, it may be a useful predictive marker of recurrence in resected HCC patients.