Loss of ARID1A expression in endometrial samplings is associated with the risk of endometrial carcinoma
Loss of ARID1A expression in endometrial samplings is associated with the risk of endometrial carcinoma
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DOI：
10.1016/j.ygyno.2018.06.025
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发表时间：
2018-09-01
影响因子：
4.7
通讯作者：
Tanner, Edward J., III
中科院分区：
文献类型：
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作者：
Yen, Ting-Tai;Miyamoto, Tsutomu;Tanner, Edward J., III
目标。染色质重塑基因ARID1A的失活体细胞突变在子宫内膜样子宫内膜癌（EEC）中很常见，但在复杂非典型增生（CAH）中很少见。我们的目的是确定在从CAH到EEC的肿瘤进展过程中ARIDIA丢失的临床意义，并评估其作为预测癌症生物标志物的作用。在队列A中，在显示CAH的子宫内膜取样（活检/刮除）标本中评估ARID1A的免疫反应性，以确定ARID1A表达是否与随后子宫切除术中EEC的存在相关。在队列B中，评估了伴有CAH和EEC的子宫切除术标本中ARID1A的免疫反应性，以评估ARID1A在这两个成分中的表达的一致性。在队列A中，31%的术前诊断为CAH的子宫切除术患者的子宫内膜取样标本中发现ARID1A免疫反应性缺失。94%的子宫内膜取样标本中ARID1A缺失的患者在子宫切除标本中发现了EEC，而只有15%的患者保留了ARID1A表达（P < 0.0001）。没有观察到ARID1A表达与人口统计学特征之间的关联。在队列B中，45例同时患有CAH/EEC的子宫切除术标本中，14例（31%）的患者在EEC成分中完全丧失了ARID1A表达。在这14例患者中，50%的患者在CAH组分中也有ARID1A免疫反应性丧失。ARID1A免疫染色可能与子宫切除术前子宫内膜取样发现的CAH患者的恶性转化和并发EEC的存在相关。进一步研究确定ARID1A表达作为组织生物标志物的潜在效用是有必要的。(C) 2018爱思唯尔公司版权所有。
Objectives. Inactivating somatic mutations of ARID1A, a chromatin remodeling gene, are common in endometrioid endometrial carcinoma (EEC) but rare in complex atypical hyperplasia (CAH). Our objectives were to determine the clinical significance of ARIDIA loss during tumor progression from CAH to EEC and to assess its role as a predictive cancer biomarker.Methods. In cohort A, ARID1A immunoreactivity was evaluated in endometrial sampling (biopsy/curettage) specimens showing CAH to determine whether ARID1A expression correlates with the presence of EEC at subsequent hysterectomy. In cohort B, ARID1A immunoreactivity was evaluated in the hysterectomy specimens with concurrent CAH and EEC to assess for the concordance of ARID1A expression in both components.Results. In cohort A, loss of ARID1A immunoreactivity was identified in the endometrial sampling specimen of 31% of patients undergoing hysterectomy for a preoperative diagnosis of CAH. EEC was identified in the hysterectomy specimen of 94% of patients with loss of ARID1A in the endometrial sampling specimen while only 15% of patients with retained ARID1A expression (P < 0.0001). No association was observed between ARID1A expression and demographic characteristics. In cohort B, 14 (31%) of 45 patients with concurrent CAH/EEC in their hysterectomy specimens had complete loss of ARID1A expression in the EEC components. Among these 14 patients, 50% also had loss of ARID1A immunoreactivity in the CAH component.Conclusions. ARID1A immunostaining may correlate with malignant transformation and the presence of concurrent EEC in patients with CAH identified at pre-hysterectomy endometrial sampling. Further investigation to determine the potential utility of ARID1A expression as a tissue biomarker is warranted. (C) 2018 Elsevier Inc. All rights reserved.