The Center for Translational and Applied Genomics (CTAG) at the British Columbia (BC) Cancer Agency, Vancouver, BC, Canada.
J Pathol. 2011 Jul;224(3):328-33. doi: 10.1002/path.2911. Epub 2011 May 18.
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.
ARID1A 基因突变和相应蛋白 BAF250a 的缺失最近被描述为卵巢透明细胞癌和子宫内膜样癌的常见事件。为了确定 BAF250a 的缺失是否在其他恶性肿瘤中常见，我们对 3000 多种癌症（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）的组织微阵列（TMA）进行了 BAF250a 的免疫组织化学（IHC）检测。我们发现 BAF250a 的缺失在子宫内膜癌中很常见，但在其他类型的恶性肿瘤中却不常见，在子宫内膜的 1 级或 2 级中观察到 29%（29/101）和 3 级中观察到 39%（44/113）的子宫内膜样癌，在 18%（17/95）的子宫浆液性癌和 26%（6/23）的子宫透明细胞癌中观察到 BAF250a 的缺失。由于子宫内膜癌显示出 BAF250a 的缺失，我们对 9 例非典型增生和 10 例非典型子宫内膜异位症的全组织切片进行了 BAF250a 表达的染色。在 9 例复杂非典型子宫内膜增生中，所有病例均显示 BAF250a 表达；然而，在 10 例非典型子宫内膜异位症（卵巢透明细胞癌和子宫内膜样癌的潜在前驱病变）中，有 1 例在非典型区域出现 BAF250a 染色缺失，而在非典型子宫内膜异位症区域保留染色。这是唯一一例作为子宫内膜样癌复发的病例，表明 BAF250a 的缺失可能是癌变过程中的早期事件。由于 BAF250a 的缺失在子宫内膜癌中的发生率与卵巢透明细胞癌和子宫内膜样癌相似，而在其他恶性肿瘤中不常见，因此我们得出结论，BAF250a 的缺失是来源于子宫内膜腺上皮的癌的一个特殊特征。
