CTNNB1 mutations and β-catenin expression in endometrial carcinomas

被引:116
|
作者
Machin, P [1 ]
Catasus, L [1 ]
Pons, C [1 ]
Muñoz, J [1 ]
Matias-Guiu, X [1 ]
Prat, J [1 ]
机构
[1] Hosp Santa Creu, Dept Pathol, Sant Pau 08025, Barcelona, Spain
关键词
endometrial adenocarcinoma; beta-catenin; CTNNB1; immunohistochemistry; gene mutations; cyclin D1; matrix metalloproteinase-7; microsatellite instability; tumor progression;
D O I
10.1053/hupa.2002.30723
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Mutations in the beta-catenin gene (CTNNB 1) with abnormal nuclear accumulation of beta-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 beta-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 beta-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 beta-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 beta-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 beta-catenin activation in ECs. Copyright 2002, Else-vier Science (USA). All rights reserved.
引用
收藏
页码:206 / 212
页数:7
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