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卵巢透明细胞癌和子宫内膜样癌、连续性子宫内膜异位症及良性子宫内膜异位症中的ARID1A通路

The ARID1A pathway in ovarian clear cell and endometrioid carcinoma, contiguous endometriosis, and benign endometriosis.

作者信息

Chene Gautier, Ouellet Veronique, Rahimi Kurosh, Barres Veronique, Provencher Diane, Mes-Masson Anne Marie

机构信息

Centre de Recherche du Centre hospitalier de l'Université de Montréal and the Institut du Cancer de Montréal, Montréal, QC, Canada; Department of Gynecology, HFME, Lyon, France.

Centre de Recherche du Centre hospitalier de l'Université de Montréal and the Institut du Cancer de Montréal, Montréal, QC, Canada.

出版信息

Int J Gynaecol Obstet. 2015 Jul;130(1):27-30. doi: 10.1016/j.ijgo.2015.02.021. Epub 2015 Apr 11.

Abstract

OBJECTIVE

To assess ARID1A-encoded protein (BAF250a) and phosphorylated AKT (pAKT) expression, apoptosis, and the DNA damage response pathway in endometrioid and clear cell ovarian cancers (endometriosis-associated ovarian cancers [EAOCs]), and benign endometriotic ovarian cysts.

METHODS

In a retrospective study, tissue samples were reviewed from patients who had undergone surgery for EAOC or endometriotic ovarian cysts at a center in Montreal, QC, Canada, between 2000 and 2012. A tissue microarray including cases of endometrioid carcinoma, clear cell carcinoma, contiguous endometriosis (i.e. apparently benign endometriosis near the EAOC), and benign endometriotic ovarian cysts, was analyzed for the expression of various proteins.

RESULTS

Loss of BAF250a expression was seen in 13 (22%) of 59 endometrioid cancers, 17 (47%) of 36 clear cell cases, 8 (44%) of 18 contiguous endometriosis cases, and 3 (8%) of 66 benign endometriotic ovarian cysts. In tissues showing loss of BAF250a, expression of pAKT, γH2AX, BIM, and BAX was higher in EAOC and contiguous endometriosis than in benign endometriosis (P<0.05), whereas expression of pATM, pCHK2, and Bcl2 was low. All proteins except for Bcl2 showed low expression in benign endometriosis.

CONCLUSION

Loss of ARID1A-encoded protein seems to be an early event in EOAC, along with pAKT activation, alteration of γH2AX, and concomitant activation of the apoptosis pathway.

摘要

目的

评估子宫内膜样癌和透明细胞卵巢癌(子宫内膜异位症相关卵巢癌[EAOC])以及良性子宫内膜异位卵巢囊肿中ARID1A编码蛋白(BAF250a)和磷酸化AKT(pAKT)的表达、细胞凋亡及DNA损伤反应途径。

方法

在一项回顾性研究中,对2000年至2012年期间在加拿大魁北克省蒙特利尔市一家中心接受EAOC或子宫内膜异位卵巢囊肿手术的患者的组织样本进行了复查。对一个组织微阵列进行分析,该微阵列包括子宫内膜样癌、透明细胞癌、相邻子宫内膜异位症(即EAOC附近明显良性的子宫内膜异位症)和良性子宫内膜异位卵巢囊肿病例,以检测各种蛋白质的表达。

结果

在59例子宫内膜样癌中有13例(22%)、36例透明细胞癌中有17例(47%)、18例相邻子宫内膜异位症中有8例(44%)以及66例良性子宫内膜异位卵巢囊肿中有3例(8%)出现BAF250a表达缺失。在显示BAF250a缺失的组织中,EAOC和相邻子宫内膜异位症中pAKT、γH2AX、BIM和BAX的表达高于良性子宫内膜异位症(P<0.05),而pATM、pCHK2和Bcl2的表达较低。除Bcl2外,所有蛋白质在良性子宫内膜异位症中均呈低表达。

结论

ARID1A编码蛋白的缺失似乎是EOAC中的一个早期事件,同时伴有pAKT激活、γH2AX改变以及凋亡途径的伴随激活。

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