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A survey of c-MET expression and amplification in 287 patients with hepatocellular carcinoma.

AbstractBACKGROUND:
c-N-Methyl-N'-nitro-N-nitroso-guanidine HOS transforming gene (c-MET) is a new potential drug target for treatment of patients with hepatocellular carcinoma (HCC), and a recent study of a c-MET inhibitor in such patients has shown promising results. In the present study, we investigated the incidence of c-MET overexpression and its prognostic impact.
MATERIALS AND METHODS:
Tumor tissue microarrays were used to detect the expression of c-MET in samples from 287 patients with HCC who underwent surgical resection at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features of HCC, and investigated recurrence-free survival (RFS) and HCC-specific survival according to the level of c-MET expression. Additionally, we explored the correlation between c-MET protein overexpression, and MET mRNA expression and copy number variation.
RESULTS:
Most patients in the present study were male (n=297, 82.6%), with Child-Pugh class A liver function (n=286, 99.7%) and hepatitis B viral infection (n=217, 75.6%). c-MET overexpression was observed in 80 patients (27.9%), and was not associated with Edmondson grade, tumor size, microvascular invasion, major portal vein invasion or stage. In addition, c-MET expression levels did not affect RFS or HCC-specific survival. c-MET expression was weakly correlated with c-MET copy number variation (r=0.255, p<0.001), but more than half of all patients with c-MET overexpression had a neutral c-MET copy number. c-MET protein expression was very weakly but significantly positively correlated with its mRNA expression (r=0.199, p=0.002).
CONCLUSION:
c-MET overexpression did not have any prognostic impact on recurrence or survival of patients with HCC undergoing surgical resection. However, 27.9% of patients who had c-MET overexpression could be considered candidates for treatment with c-MET inhibitor.
AuthorsSu Jin Lee, Jeeyun Lee, Insuk Sohn, Mao Mao, Wang Kai, Cheol-Keun Park, Ho Yeong Lim
JournalAnticancer research (Anticancer Res) Vol. 33 Issue 11 Pg. 5179-86 (Nov 2013) ISSN: 1791-7530 [Electronic] Greece
PMID24222167 (Publication Type: Journal Article)
Chemical References
  • Biomarkers, Tumor
  • RNA, Messenger
  • MET protein, human
  • Proto-Oncogene Proteins c-met
Topics
  • Adolescent
  • Adult
  • Aged
  • Biomarkers, Tumor (analysis)
  • Carcinoma, Hepatocellular (genetics, metabolism, mortality, surgery)
  • DNA Copy Number Variations
  • Female
  • Follow-Up Studies
  • Gene Amplification
  • Humans
  • Immunoenzyme Techniques
  • Liver Neoplasms (genetics, metabolism, mortality, surgery)
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local (genetics, metabolism, mortality, surgery)
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-met (genetics, metabolism)
  • RNA, Messenger (genetics)
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Young Adult

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