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

Int J Clin Oncol. 2013 Apr;18(2):207-13. doi: 10.1007/s10147-011-0361-9. Epub 2012 Jan 5.


Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Gene Amplification
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-met / genetics*


  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-met