Critical role of c-Met and Ki67 in progress of biliary carcinoma.

The purpose of this study was to evaluate the pattern of expression of c-Met and Ki67 in several components of biliary carcinoma. Fourteen surgically resected samples, including five intrahepatic cholangiocarcinomas, five gallbladder carcinomas, and four extrahepatic bile duct carcinomas, were subjected to immunohistochemistry with primary antibodies. In all 13 cases, intraductal neoplastic components showed diffuse staining for c-Met localized in the cell membrane, whereas 10 of the 14 cases lacked expression of c-Met in the corresponding invasive components. In four cases, invasive components composed of undifferentiated carcinoma (n = 2), signet-ring cell carcinoma (n = 1), and squamous cell carcinoma (n = 1) showed nuclear or perinuclear staining for c-Met. Conversely, 11 of the 13 cases did not express Ki67 in intraductal neoplastic components, whereas corresponding invasive components showed diffuse nuclear staining in all 14 cases. A comparison of the patterns of expression between c-Met and Ki67 at the boundary between intraductal and invasive components clearly demonstrated the complementary expression of c-Met and Ki67. Our results suggested that c-Met is involved in early events of carcinogenesis and Ki67 is involved in the formation of invasive carcinoma. However, exceptional cases were also observed, which might be associated with specificity for histologic subtypes and malignant potential.