β-Catenin mutation and expression analysis in ovarian cancer: Exon 3 mutations and nuclear translocation in 16% of endometrioid tumours

The molecular mechanisms involved in the generation of epithelial ovarian cancers are poorly understood, but evidence suggests that the different histological subtypes may arise from independent tumorigenic events. β-Catenin is emerging as an important oncogene in the transformation of a number of epithelial cancers, and mutations have been reported in a small study of endometrioid ovarian adenocarcinomas. Mutations in the NH2-regulatory domain of β-catenin stabilise the cytoplasmic levels of this protein, which promotes up-regulation of the β-catenin–T-cell factor–lymphoid enhancer factor transcriptional complex. We report here β-catenin (CTNNB1) exon 3 mutation analysis in 149 epithelial ovarian carcinomas. This revealed 10/63 (16%) endometrioid ovarian tumours with activating mutations of the β-catenin gene. All mutations were missense changes within the GSK3β consensus site, affecting serine residues at codons 33 and 37 and glycine at codon 34. Immuno-histochemical analysis identified cytoplasmic stabilisation and nuclear translocation in those endometrioid tumours with mutations. This phenotypic change was also identified in 3 other endometrioid tumours that did not have somatic mutations within exon 3 of CTNNB1. Stabilisation of the free, monomeric pool of β-catenin and the probable resulting constitutive activation of its Tcf-associated transcriptional complex appears to be a specific oncogenic event in endometrioid ovarian adenocarcinoma. Int. J. Cancer 82:625–629, 1999. © 1999 Wiley-Liss, Inc.