MUTATIONS IN THE BETA-CATENIN GENE (CTNNB1) IN ENDOMETRIOID OVARIAN CARCINOMAS

Mutations of the beta-catenin gene (CTNNB1) have recently been implica ted in the initiation of some colon carcinomas and melanomas. In these tumors, beta-catenin abnormally accumulates in the cell nuclei, In an ongoing immunohistochemical study of the cadherin-catenin complex pro tein expression in ovarian carcinomas, we observed beta-catenin in tum or cell nuclei in some cases; this prompted us to study whether or not this abnormal Immunostaining pattern was due to mutation in the beta- catenin gene itself. This study examines beta-catenin immunohistochemi cal expression in 40 stage I and II ovarian borderline tumors and carc inomas of the most common histological types. Membrane expression was heterogeneous in all 40 cases, However, the cytoplasm and nucleus of f ive (one borderline tumor rind four carcinomas) of the six endometrioi d lesions contained beta-catenin expression, PCR and sequencing analys es of a 200-by fragment of exon 3 of the CTNNB1 gene, encompassing til e sequence for glycogen synthetase kinase-3 beta phosphorylation, were performed in 11 tumors. Heterozygous substitution mutations at codon 37 in two cases (S37F and S37C) and at codon 41 in one case (T41A) mer e found in three endometrioid lesions (one borderline tumor and two ca rcinomas) with abnormal beta-catenin expression, Three endometrioid ca rcinomas and five tumors of other histological types analyzed showed n ormal DNA sequences, These results implicate beta-catenin gene mutatio ns in ovarian malignant transformation with a characteristic phenotype : endometrioid ovarian carcinoma.