Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.
Mod Pathol. 2012 Jun;25(6):885-92. doi: 10.1038/modpathol.2011.217. Epub 2012 Feb 3.
Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n=136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n=3/20, 15%) and one deep-infiltrating endometriosis sample (n=1/22, 5%), but in none of the peritoneal endometriosis (n=0/16) and eutopic endometrium samples (n=0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (P<0.0005), as well as peritoneal (P=0.003) and deep-infiltrating endometriosis (P=0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied.
抑癌基因 ARID1A 的突变导致 BRG 相关因子 250a（BAF250a）的蛋白表达缺失，BAF250a 是转录调控人 SWI/SNF 复合物的一个大亚基，在细胞增殖和肿瘤抑制的控制中具有重要作用。ARID1A 突变在子宫内膜异位症相关的卵巢透明细胞癌和子宫内膜样癌中特别频繁，最近被描述为子宫内膜异位症向癌症转化的一个可能的关键机制和早期步骤。在这里，我们在包括 74 例子宫内膜异位症和 30 例子宫内膜样本的组织微阵列中检查了 BAF250a 的免疫组织化学表达模式。卵巢癌样本（n=136）作为对照。由于某些部位组织不足，可评估 90/104（87%）例子宫内膜异位症和 95/104（91%）例子宫内膜病例的上皮 BAF250a 表达，以及 95/104（91%）例子宫内膜病例的基质 BAF250a 表达。由于某些部位组织不足，三个卵巢子宫内膜样囊肿（n=3/20，15%）和一个深部浸润性子宫内膜异位症样本（n=1/22，5%）中观察到完全缺乏 BAF250a 表达，但在任何腹膜子宫内膜异位症（n=0/16）和在位子宫内膜样本（n=0/30）中均未观察到。比较平均免疫反应评分显示，与正常子宫内膜相比，子宫内膜样囊肿中 BAF250a 的表达率显著降低（P<0.0005），腹膜（P=0.003）和深部浸润性子宫内膜异位症（P=0.02）也是如此。我们的数据表明，一些子宫内膜异位症病变中可观察到 BAF250a 表达完全缺失，特别是在子宫内膜样囊肿中。此外，我们报告说，以细胞簇的形式发生 BAF250a 表达部分缺失，表明这些细胞中 BAF250a 表达的克隆缺失。一些子宫内膜样囊肿中肿瘤抑制蛋白 BAF250a 的表达缺失可能表明这些病例存在恶性转化的风险，这在确定个体化治疗策略方面可能很重要。然而，它作为子宫内膜异位症预后参数的作用和价值需要进一步研究。
