PIK3CA mutations and amplification in endometrioid endometrial carcinomas: relation to other genetic defects and clinicopathologic status of the tumors

被引:46
作者
Konopka, Bozena [1 ,2 ]
Janiec-Jankowska, Aneta [1 ,2 ]
Kwiatkowska, Ewa [1 ,2 ]
Najmola, Urszula [1 ,2 ]
Bidzinski, Maniusz [2 ,3 ]
Olszewski, Wlodzimierz [2 ,4 ]
Goluda, Cyprian [5 ]
机构
[1] Maria Sklodowska Curie Mem Canc Ctr, Dept Endocrinol, PL-02781 Warsaw, Poland
[2] Inst Oncol, PL-02781 Warsaw, Poland
[3] Maria Sklodowska Curie Mem Canc Ctr, Dept Gynecol Oncol, PL-02781 Warsaw, Poland
[4] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol, PL-02781 Warsaw, Poland
[5] Med Univ, Dept Gynecol 2, PL-50528 Wroclaw, Poland
关键词
Endometrial carcinoma; Hyperplasia; PIK3CA; PTEN; Mutation; Amplification; CANCER-SPECIFIC MUTATIONS; HIGH-FREQUENCY; PTEN; PATHWAY; EXPRESSION; OVARIAN;
D O I
10.1016/j.humpath.2010.01.030
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Alterations of the PIK3CA gene occur in endometrial carcinomas, but their role in the carcinogenesis of those malignancies is still poorly understood. In this study, PIK32A mutations and amplification in 196 endometrioid endometrial carcinomas and 20 endometrial hypetplasias were assessed by single-strand conformation polymorphism (PCR-SSCP), sequencing, and quantitative polymerase chain reaction. Results were correlated with mutations in the PTEN, KRAS, and CTNNB1 genes and with the clinicopathologic parameters of the tumors. PIK3CA mutations were found in 39 (20%) carcinomas. Six new mutations were identified. No PIK3CA mutations were found in endometrial hyperplasias. PIK3CA amplification was observed in 24 (12.2%) carcinomas and in 2 (10%) hyperplasias. The PIK3CA mutations and amplifications (with the exception of 6 cases) occurred independently. PIK3CA mutations were significantly associated with PTEN mutations (P = .0414) and tended to be associated with CTNNB1 (P = .0833), but not with KRAS mutations. Conversely, the PIK3CA amplifications significantly negatively correlated with PTEN mutations (P = .0038) and did not coexist with CTNNB1 and KRAS mutations. The PIK3CA mutations were significantly associated with poorly differentiated tumors (P = .0423). Interestingly, PIK3CA amplifications, but not mutations, were strongly associated with older age (>= 63 years, P = .0018). Our data show that mutations and amplification of PIK3CA are significant genetic alterations in endometrioid endometrial carcinomas associated with adverse clinicopathologic parameters (grade and stage). These data also demonstrate that PIK3CA mutations cooperate with PTEN mutations, suggesting an additive effect to PTEN, whereas PIK3CA amplification can, as an isolated event, enable the development of those tumors. Moreover, for the first time, a possible role of PIK3CA amplification in initiation and progression of endometrial carcinomas in older women is suggested, but this preliminary suggestion requires further research. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:1710 / 1719
页数:10
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