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


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).


CONCLUSIONS
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.
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong Gangnam-gu, Seoul 135-710, Korea. Tel: +82 234102766 ckpark@skku.edu.
Su Jin
SJ
Lee
Jeeyun
J
Lee
Insuk
I
Sohn
Mao
M
Mao
Wang
W
Kai
Cheol-Keun
CK
Park
Ho Yeong
HY
Lim
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D056915:DNA Copy Number Variations; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D009367:Neoplasm Staging; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
Hepatocellular carcinoma; c-MET; copy number variation; immunohistochemistry; prognosis