Mutational analysis of beta-catenin gene in Japanese ovarian carcinomas: Frequent mutations in endometrioid carcinomas

To investigate the contribution of the beta-catenin gene to the development of ovarian carcinomas, mutational analysis of exon 3 of the beta-catenin g ene was conducted. We analyzed 61 primary ovarian carcinomas, consisting of 49 non-endometrioid-type and 12 endometrioid-type tumors, for genetic alte ration of the beta-catenin gene, Five carcinomas showed beta-catenin mutati ons (S37C, T41I, T41A), including 4 (33%) of 12 endometrioid-type tumors an d 1 (14%) of 7 mucinous-type tumors. All of these mutations altered at the serine/threonine residues that are potential sites of GSK3-beta phosphoryla tion, We detected no carcinomas with interstitial deletion involving exon 3 of beta-catenin, Furthermore, we immunohistochemically studied 27 of the 6 1 ovarian carcinomas. Both nuclear and cytoplasmic beta-catenin expressions were demonstrated in 3 of the 27 ovarian carcinomas for which tissue sampl es were available for examination. All 4 cases exhibited mutations in exon 3 of beta-catenin, including a mucinous carcinoma. Our results suggested th at beta-catenin gene mutation at potential GSK3-beta phosphorylation sites results in accumulation of beta-catenin protein within the cells and its tr anslocation to nuclei. Accumulated beta-catenin protein may be involved in the development of endometrioid-type ovarian carcinomas, and some mucinous- type ovarian carcinomas.