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Departmento de Anatomía Patológica, Hospital Universitario La Paz (Universidad Autónoma de Madrid), 28046 Madrid, Spain
Mutations of the ß-catenin gene (CTNNB1) have recently been implicated in the initiation of some colon carcinomas and melanomas. In these tumors, ß-catenin abnormally accumulates in the cell nuclei. In an ongoing immunohistochemical study of the cadherin-catenin complex protein expression in ovarian carcinomas, we observed ß-catenin in tumor cell nuclei in some cases; this prompted us to study whether or not this abnormal immunostaining pattern was due to mutation in the ß-catenin gene itself. This study examines ß-catenin immunohistochemical expression in 40 stage I and II ovarian borderline tumors and carcinomas of the most common histological types. Membrane expression was heterogeneous in all 40 cases. However, the cytoplasm and nucleus of five (one borderline tumor and four carcinomas) of the six endometrioid lesions contained ß-catenin expression. PCR and sequencing analyses of a 200-bp fragment of exon 3 of the CTNNB1 gene, encompassing the sequence for glycogen synthetase kinase-3ß 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) were found in three endometrioid lesions (one borderline tumor and two carcinomas) with abnormal ß-catenin expression. Three endometrioid carcinomas and five tumors of other histological types analyzed showed normal DNA sequences. These results implicate ß-catenin gene mutations in ovarian malignant transformation with a characteristic phenotype: endometrioid ovarian carcinoma.
1 This work was supported in part by Fondo de Investigación Sanitaria Grant 95/0849.
2 To whom requests for reprints should be addressed, at Departamento de Anatomía Patológica, Hospital Universitario La Paz (Universidad Autónoma de Madrid), Paseo de la Castellana 261, 28046 Madrid, Spain.
Received 11/20/97. Accepted 2/18/98.
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