Prognostic significance of overexpression of c-Met oncoprotein in cholangiocarcinoma

Abstract

Cholangiocarcinoma (CC) is a highly malignant carcinoma. We attempted to clarify the prognostic significance of c-Met overexpression and its association with clinicopathological factors in patients with CC. One hundred and eleven patients with intrahepatic CC (IHCC) and 136 patients with extrahepatic CC (EHCC) who had undergone curative surgery were divided immunohistologically into c-Met^high and c-Met^low groups. Clinicopathological factors and outcomes were compared between the groups. c-Met and epidermal growth factor receptor (EGFR) expression was also examined in 10 CC cell lines. The positivity of c-Met was 45.0% in IHCC and 68.4% in EHCC; c-Met^high expression was demonstrated in 11.7% of IHCC and 16.2% of EHCC. c-Met^high expression was significantly correlated with the 5-year survival rate for CC overall (P=0.0046) and for IHCC (P=0.0013), histopathological classification in EHCC, and for EGFR overexpression in both IHCC and EHCC. Coexpression and coactivation of c-Met and EGFR were also observed in CC cell lines. Multivariate analysis revealed that c-Met^high expression was an independent predictor of poor overall and disease-free survival in patients with IHCC. c-Met overexpression is associated with EGFR expression and is a poor prognostic factor in CC.