Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation?
Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation?
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DOI：
10.1038/modpathol.2011.217
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发表时间：
2012-06-01
期刊：
影响因子：
7.5
通讯作者：
Imesch, Patrick
中科院分区：
文献类型：
--
作者：
Samartzis, Eleftherios P.;Samartzis, Nicolas;Imesch, Patrick
肿瘤抑制基因ARID1A突变导致brg相关因子250a （BAF250a）蛋白表达缺失，BAF250a是调控人类SWI/SNF复合物转录的一个大亚基，在控制细胞增殖和肿瘤抑制中起重要作用。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尤为常见，最近被认为是子宫内膜异位症转化为癌症的一个可能的关键机制和早期步骤。本研究通过组织芯片检测了74例子宫内膜异位症和30例子宫内膜样本中BAF250a的免疫组化表达模式。卵巢癌样本（n = 136）作为对照。在90/104（87%）的子宫内膜异位症和由于某些部位缺乏足够组织的子宫内膜病例中，上皮细胞BAF250a表达可评估，基质细胞BAF250a表达可评估95/104（91%）的子宫内膜异位症。在3例子宫内膜异位症（n= 3/ 20,15%）和1例深浸润性子宫内膜异位症（n= 1/ 22,5%）中观察到BAF250a完全缺失表达，但在腹膜子宫内膜异位症（n= 0/16）和异位子宫内膜样本（n= 0/30）中均未观察到BAF250a表达。比较平均免疫反应性评分显示，BAF250a在子宫内膜异位瘤中的表达率明显低于正常子宫内膜(P
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