Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas
Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas
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DOI：
10.1002/path.2911
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发表时间：
2011-07-01
影响因子：
7.3
通讯作者：
Huntsman, David G.
中科院分区：
文献类型：
--
作者：
Wiegand, Kimberly C.;Lee, Anna F.;Huntsman, David G.
ARID 1A基因的突变和相应蛋白BAF 250 a的缺失最近被描述为卵巢透明细胞癌和卵巢样癌的常见事件。为了确定BAF 250 a丢失是否在其他恶性肿瘤中常见，在超过3000种癌症的组织微阵列（TMA）上进行BAF 250 a的免疫组织化学（IHC），所述癌症包括乳腺癌、肺癌、甲状腺癌、子宫内膜癌、肾癌、胃癌、口腔癌、宫颈癌、胰腺癌、结肠癌和直肠癌，以及子宫内膜间质肉瘤、胃肠道间质肿瘤、性索间质肿瘤和四种主要类型的淋巴瘤（弥漫性大B细胞淋巴瘤、原发性纵隔B细胞淋巴瘤、套细胞淋巴瘤和滤泡性淋巴瘤）。我们发现BAF 250 a丢失在子宫内膜癌中很常见，但在其他类型的恶性肿瘤中不常见，在子宫内膜的1级或2级中观察到29%（29/101）和39%（44/113）的3级子宫内膜样癌，18%（17/95）的子宫浆液性癌和26%（6/23）的子宫透明细胞癌。由于子宫内膜癌显示BAF 250 a丢失，我们对9例不典型增生和10例不典型子宫内膜异位症的全组织切片进行BAF 250 a表达染色。在9例复杂的子宫内膜非典型增生中，所有病例均显示BAF 250 a表达;然而，在10例非典型子宫内膜异位症（卵巢透明细胞癌和卵巢癌样癌的假定前驱病变）中，1例显示非典型区域BAF 250 a染色缺失，非典型子宫内膜异位症区域染色保留。这是唯一的情况下，复发的类胶质瘤，表明BAF 250 a的损失可能是一个早期事件的致癌作用。由于BAF 250 a的损失是在子宫内膜癌中看到的透明细胞和类卵巢癌中看到的类似的速度，是罕见的在其他恶性肿瘤中，我们得出结论，BAF 250 a的损失是一个特殊的功能产生于子宫内膜腺上皮癌。版权所有（C）2011大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Mutation of the ARID1A gene and loss of the corresponding protein BAF250a has recently been described as a frequent event in clear cell and endometrioid carcinomas of the ovary. To determine whether BAF250a loss is common in other malignancies, immunohistochemistry (IHC) for BAF250a was performed on tissue microarrays (TMAs) in more than 3000 cancers, including carcinomas of breast, lung, thyroid, endometrium, kidney, stomach, oral cavity, cervix, pancreas, colon and rectum, as well as endometrial stromal sarcomas, gastrointestinal stromal tumours, sex cord-stromal tumours and four major types of lymphoma (diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, mantle cell lymphoma and follicular lymphoma). We found that BAF250a loss is frequent in endometrial carcinomas but infrequent in other types of malignancies, with loss observed in 29% (29/101) of grade 1 or 2 and 39% (44/113) of grade 3 endometrioid carcinomas of the endometrium, 18% (17/95) of uterine serous carcinomas and 26% (6/23) of uterine clear cell carcinomas. Since endometrial cancers showed BAF250a loss, we stained whole tissue sections for BAF250a expression in nine cases of atypical hyperplasia and 10 cases of atypical endometriosis. Of the nine cases of complex atypical endometrial hyperplasia, all showed BAF250a expression; however, of 10 cases of atypical endometriosis (the putative precursor lesion for ovarian clear cell and endometrioid carcinoma), one case showed loss of staining for BAF250a in the atypical areas, with retention of staining in areas of non-atypical endometriosis. This was the sole case that recurred as an endometrioid carcinoma, indicating that BAF250a loss may be an early event in carcinogenesis. Since BAF250a loss is seen in endometrial carcinomas at a rate similar to that seen in ovarian carcinomas of clear cell and endometrioid type, and is uncommon in other malignancies, we conclude that loss of BAF250a is a particular feature of carcinomas arising from endometrial glandular epithelium. Copyright (C) 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.