MET is a predictive factor for late recurrence but not for overall survival of early stage hepatocellular carcinoma

The MET and RON receptors are tyrosine kinases that form a non-covalent complex on the cell surface that functions in several steps of tumor progression. The purpose of this study was to determine the clinical significance of MET and RON expression on long-term survival and recurrence after curative resection in a large cohort of hepatocellular carcinoma (HCC) patients. We performed immunohistochemical analyses on microarrays of the tumors using antibodies against MET and RON. We evaluated the prognostic value of biomarker expression using Cox regression and the KaplanMeier method in 490 HCC patients. MET-positive patients had higher overall recurrence rates than MET-negative patients (P=0.041); however, MET positivity was not associated with overall survival (OS) (P=0.249). RON was not associated with overall recurrence rates and OS. MET was independently associated with late but not early phase recurrence. Particularly, the prognostic significance of MET is limited in early stage disease. MET+/RON+ patients had higher overall recurrence rates than those with the other expression patterns (P=0.071), although the result did not reach statistical significance. Immunohistological activation of MET expression has no prognostic significance for OS in patients with HCC. However, MET positivity was correlated with late recurrence after HCC resection in early stage disease.