Background: AT-rich interaction domain 1A (ARID1A) has been proposed as a new biomarker for predicting response to immune checkpoint inhibitors (ICIs). The predictive value of ARID1A for predicting ICI effectiveness has not been reported for endometrial cancer. Therefore, we investigated whether ARID1A negativity predicts ICI effectiveness for endometrial cancer treatment. Methods: We evaluated ARID1A expression, tumor-infiltrating lymphocytes (CD8+), and immune checkpoint molecules (PD-L1/PD-1) by immunostaining endometrial samples from patients with endometrial cancer. Samples in which any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) were determined to be negative via immunostaining were excluded. In the ARID1A-negative group, microsatellite instability (MSI) status was confirmed via MSI analysis. Results: Of the 102 samples investigated, 25 (24.5%) were ARID1A-negative. CD8 and PD-1 expression did not differ significantly between the ARID1A-negative group and the ARID1A-positive group; however, the ARID1A-negative group showed significantly lower PD-L1 expression. Only three samples (14.2%) in the ARID1A-negative group showed high MSI. Sanger sequencing detected three cases of pathological mutation in the MSH2-binding regions. We also established an ARID1A-knockout human ovarian endometriotic epithelial cell line (HMOsisEC7 ARID1A KO), which remained microsatellite-stable after passage. Conclusion: ARID1A negativity is not suitable as a biomarker for ICI effectiveness in treating endometrial cancer.
背景：富含AT结合域1A（ARID1A）已被提出作为预测免疫检查点抑制剂（ICIs）疗效的新型生物标志物。ARID1A在预测子宫内膜癌中ICI疗效的价值尚未见报道。因此，本研究探讨了ARID1A阴性是否可作为预测子宫内膜癌ICI治疗效果的指标。方法：通过对子宫内膜癌患者样本进行免疫组化染色，评估ARID1A表达、肿瘤浸润淋巴细胞（CD8+）及免疫检查点分子（PD-L1/PD-1）。通过免疫组化检测四种错配修复蛋白（MLH1、MSH2、MSH6和PMS2）任一为阴性的样本被排除。在ARID1A阴性组中，通过微卫星不稳定性（MSI）分析确认MSI状态。结果：在研究的102例样本中，25例（24.5%）为ARID1A阴性。CD8和PD-1表达在ARID1A阴性组与阳性组间无显著差异；然而，ARID1A阴性组的PD-L1表达显著降低。ARID1A阴性组中仅3例样本（14.2%）显示高微卫星不稳定性。Sanger测序检测到3例MSH2结合区域存在病理突变。此外，本研究成功构建了ARID1A敲除的人卵巢子宫内膜异位上皮细胞系（HMOsisEC7 ARID1A KO），该细胞系在传代后仍保持微卫星稳定。结论：ARID1A阴性不适合作为预测子宫内膜癌ICI治疗效果的生物标志物。
肿瘤(癌症)患者之家