Different In Situ Expression of Insulin-Like Growth Factor Type II in Hepatocellular Carcinoma

Reexpression of the insulin-like growth factor type II (IGF-II) gene has recently been described in hepatocellular carcinoma (HCC). In this study, we used a nonisotopic in situ hybridization method to analyze the expression of IGF-II mRNA in a series of 28 HCCs arising on cirrhotic and noncirrhotic livers. An immunohistochemical method was used to detect IGF-II peptide. Hepatitis B virus (HBV) status and the histological differentiation degree were also evaluated. Increased expression of IGF-II mRNA was found in 4 of 28 HCCs, and 7 of 17 cirrhotic patients showed IGF-II mRNA in the cirrhotic nodules surrounding the HCC. A slightly higher rate of positivity for IGF-II mRNA was found in the HBV-negative patients than in HBV-positive ones. Positive immunostaining for the IGF-II peptide in the HCC and/or in surrounding cirrhotic nodules was found in 10 of 28 cases. The normal hepatocytes of the noncirrhotic patients were always negative for IGF-II peptide and mRNA. The similarities between our results and those from experimental models in woodchucks seem to support the concept that heterogeneous phenotypic groups could exist in human HCCs.