Amplification and overexpression of the MET gene in intrahepatic cholangiocarcinoma correlate with adverse pathological features and worse clinical outcome

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary hepatic malignancy, and remains a challenge to treat. At the molecular level, the hepatocyte growth factor/MET pathway is one of the most commonly activated signaling pathways in malignancies. Several studies have reported MET overexpression in human iCCAs, at varying frequencies. However, there is no consensus regarding the impact of MET overexpression on prognosis. The correlation between MET overexpression and gene amplification in iCCAs has not been explored. We obtained tissue samples from 86 patients with primary iCCAs, and performed immunohistochemical analysis of MET expression. Quantitative real-time polymerase chain reaction was also performed to examine MET amplification. MET overexpression was found in 39 of 86 cases (45.35%). It was significantly associated with older age, presence of hepatolithiasis, higher cancer stage, and more advanced primary tumor. MET overexpression was also a predictive factor for adverse outcome with shorter disease-free survival. MET amplification was detected in 10 cases of 84 cases (11.90%), and was significantly associated with larger tumor size (more than 5 cm) and shorter overall survival. There was no significant correlation between MET overexpression and gene amplification. Revealing the clinicopathological features of MET overexpression and amplification would assist in the development of personalized treatment for iCCAs.