Accumulation of beta-catenin in the cytoplasm and the nuclei during the early hepatic tumorigenesis

Hepatocellular carcinomas (HCCs) are thought to develop as well-differentia ted tumors and progress to less-differentiated tumors. However, the genetic changes underlying the development and progression of HCCs are not well un derstood. Recent studies have shown frequent beta -catenin gene activation in HCCs by somatic alterations involving exon 3, resulting in the activatio n of the Wnt/Wingless signal transduction pathway. However, the exact proce ss in which activation of Wnt/Wingless signal transduction pathway occurs d uring hepatic tumorigenesis remains to be elucidated. The aim of the presen t study was to investigate at what stage of hepatocellular tumorigenesis th is pathway was activated. Altered expression of beta -catenin was investiga ted immunohistochemically with special reference to the grade of histologic al differentiation in 41 HCCs and eight dysplastic nodules. Mutational anal ysis of the beta -catenin gene with single-strand conformation polymorphism method and polymerase chain reaction amplification was related with the ex pression of this protein. beta -Catenin was expressed in the cytoplasm and the nuclei in three cases among eight dysplastic nodules, in four cases amo ng 20 well differentiated HCCs, in five cases among 15 moderately different iated HCCs, and one case among six poorly differentiated HCCs, respectively . Expression of beta -catenin in the cytoplasm and the nuclei was associate d in one case with mutation and two cases without mutation for beta -cateni n gene among 11 screened HCCs. It was concluded that beta -catenin was accu mulated in the cytoplasm and the nuclei in pre-cancerous lesions of the liv er and might contribute, at least in part, to hepatic tumorigenesis. (C) 20 01 Elsevier Science B.V. All rights reserved.