Elsevier

Human Pathology

Volume 33, Issue 2, February 2002, Pages 206-212
Human Pathology

Original Contributions
CTNNB1 mutations and β-catenin expression in endometrial carcinomas*,**

https://doi.org/10.1053/hupa.2002.30723Get rights and content

Abstract

Mutations in the β-catenin gene (CTNNB 1) with abnormal nuclear accumulation of β-catenin have recently been identified in endometrial carcinoma (EC). Their relationship with microsatellite instability (MI) is unclear. It has been suggested that matrix metalloproteinase-7 (MMP-7) and cyclin D1 (cD) genes are targets for β-catenin activation. DNA from 73 patients with EC was obtained from tumor and normal tissue (59 endometrioid and 14 nonendometrioid). CTNNB 1 mutations in exon 3 were assessed by single-strand conformation polymorphism and DNA sequencing. The results were correlated with immunostaining for β-catenin, MMP-7, and cD. Three (CA)n repeats and mononucleotide tracts BAT 25 and BAT 26 had been previously used for MI analysis. CTNNB1 mutations were identified in 15 ECs (20.5%), all of them endometrioid carcinomas (15 of 59; 25.4%). They occurred in 6 of 19 MI-positive ECs (31.5%) and in 9 of 54 MI-negative ECs (16.6%). Eleven of the 15 CTNNB 1-mutated ECs showed β-catenin nuclear immunostaining (P <.05). MMP-7 expression (>50% cells) was observed in 23 ECs, with 7 of these showing CTNNB 1 mutations. Significant expression of cD (>50% cells) was detected in 8 ECs, with 5 of these exhibiting CTNNB 1 mutations (P <.05). The results confirm that β-catenin plays a role in endometrial carcinogenesis, particularly in endometrioid carcinomas. The results also suggest that MMP-7 and particularly cD may be targets of β-catenin activation in ECs. HUM PATHOL 33:206-212. Copyright 2002, Elsevier Science (USA). All rights reserved.

Section snippets

Tissue samples and DNA isolation

Paired tumor and normal samples from 73 consecutive patients with endometrial carcinomas were retrieved from the surgical pathology files of the Department of Pathology, Hospital Santa Creu i Sant Pau, Barcelona, Spain. Clinical information, including follow-up data, pathology reports, paraffin blocks, and slides, were available for review in all cases. All tumors were classified using the World Health Organization (WHO) criteria. Tumors were surgically staged and graded according to the

Pathological results

Fifty-nine tumors were endometrioid adenocarcinomas, and the remaining 14 were nonendometrioid carcinomas (5 papillary serous, 3 clear cell, 2 mixed papillary serous and clear cell, and 4 papillary serous with a carcinosarcoma component). Twenty-one endometrioid carcinomas were FIGO grade I, 21 were grade II, and 17 were grade III. All nonendometrioid carcinomas were high-grade tumors. Twenty-six tumors invaded less than 50% of the myometrial wall, whereas deep myometrial invasion was found in

Discussion

The gene that encodes β-catenin, CTNNB1, maps to 3p21. β-catenin is involved in the organization of tissue architecture and cell polarity and also plays a role in transcriptional activation. Cytoplasmic levels of β-catenin are regulated by the opposing actions of Wnt-1 and APC. Wnt-1 protein is a secreted growth factor that stimulates the accumulation of β-catenin, which can be incorporated into the E-cadherin-catenin unit together with E-cadherin, α-catenin, and γ-catenin in connection with

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    *

    Supported by Grants FIS 99/1145 and FIS 01/1656 and by the Asociacion Española Contra el Cancer, Spain.

    **

    Address correspondence and reprint requests to Xavier Matias-Guiu, MD, Department of Pathology, Hospital de la Santa Creu i Sant Pau, Avda Sant Antoni Ma Claret 167, 08025 Barcelona, Spain.

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