Activation of c-Src gene product in hepatocellular carcinoma is highly correlated with the indices of early stage phenotype

Background Aims: The aim of this study was to investigate whether c-Src is involved in carcinogenesis and progression of human hepatocellular carcinom a (HCC) and intrahepatic cholangiocarcinoma, Methods: We designed an immunohistochemical study using Clone 28, an antibo dy that specifically recognizes the activated form of c-Src, Results: Hepatocytes in normal liver, chronic hepatitis with or without cir rhosis, atypical adenomatous hyperplasia, as well as bile ductular cells, a nd infiltrating mononuclear cells were all negative for immunohistochemical staining for the activated c-Src, Among 87 cases of HCC tested, 40 (46%) w ere positively stained for the activated c-Src, and this positive staining was inversely correlated,vith the Ki-67 labeling index (LI) (P = 0.0031), i ntrahepatic metastasis (P = 0.0099), TNM stage (P = 0.0062), alpha-fetoprot ein (P = 0.0103) and epidermal growth factor-receptor expression (P = 0.015 3). Positive staining for the activated c-Src was more frequently observed in well- or moderateIy-differentiated carcinoma (P = 0.0256). In multivaria te analysis, the activated c-Src expression was independently related to th e Ki-67 LI (P = 0.0197), In contrast to positive staining in RCC, cholangio carcinoma were classified as negative in all 19 cases examined. Conclusions: These results strongly suggest the involvement of activated c- Src in early stages of HCC, and suggest that cholangiocarcinoma might emplo y different signaling mechanisms. (C) 2001 European Association for the Stu dy of the Liver. Published by Elsevier Science B.V. All rights reserved.