Role of deregulation of the APC-WNT-beta Catenin signaling and microsatellite instability in hepatic carcinogenesis. Preliminary results in a series of 20 sporadic hepatoblastomas and 11 non virus-related hepatocellular carcinomas

Hepatoblastoma (HB) is an embryonic tumor usually consisting of epithelial and mesenchymal components, which mainly occurs in the first years of life. The vast majority of bepatocelhilar carcinomas (HCCs) develop in cirrhotic livers; nevertheless, a small percentage of these tumors occur in the absence of HBV/I-ICV infection and cirrhosis. APC and beta-Catenin are part of the WNT-Wingless pathway. Beta-Catenin mutation and its nuclear overexpression seems to be involved in tumorigenesis and cell differentiation. We report a muhicentric study including 20 sporadic HBs and 11 non virus-related HCCs. In the HB group the mean age was 1 year and 7 months whereas in the HCC group all the patients were less than 40-years old and the tumor had developed in the absence of cirrhosis. Mutational analysis of a part of the exon 3 of the beta-Catenin gene as well as the research of microsatellite instability were performed in all HBs and HCCs. SSCP analysis and sequencing of genomic DNA showed a mutation of the beta-Catenin gene in 2 HBs (10%) and 2 HCCs (18%). A missense mutation in the codons 32 and 38 was discovered in 2 HBs while a nonsense mutation in the codon 27 and a missense mutation in the codon 32 were found in 2 HCCs. Microsatellite instability was also found in 11 HBs. Our data seems to confirm beta-Catenin involvement in liver carcinogenesis, and, interestingly, suggest that a high percentage (55%) of microsatellite instability occurs in HBs.