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微卫星不稳定性发生率低的卵巢子宫内膜样癌和透明细胞癌:一类独特的卵巢癌亚群可能从免疫检查点抑制剂与其他抗癌药物的联合治疗中获益。

Ovarian Endometrioid and Clear Cell Carcinomas with Low Prevalence of Microsatellite Instability: A Unique Subset of Ovarian Carcinomas Could Benefit from Combination Therapy with Immune Checkpoint Inhibitors and Other Anticancer Agents.

作者信息

Nonomura Yuki, Nakayama Kentaro, Nakamura Kohei, Razia Sultana, Yamashita Hitomi, Ishibashi Tomoka, Ishikawa Masako, Sato Seiya, Nakayama Satoru, Otsuki Yoshiro, Kyo Satoru

机构信息

Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 6938501, Japan.

Department of Obstetrics and Gynecology, Seirei Hamamatsu Hospital, Hamamatsu 4308558, Japan.

出版信息

Healthcare (Basel). 2022 Apr 7;10(4):694. doi: 10.3390/healthcare10040694.

Abstract

Ovarian cancer has the highest mortality rate among all gynecological malignancies; therefore, a novel treatment strategy is needed urgently. Utilizing immune checkpoint inhibitors has been considered for microsatellite instability (MSI)-high (MSI-H) tumors. However, the prevalence of MSI-H tumors in ovarian endometrioid and clear cell carcinomas remains unclear. Here, polymerase chain reaction was used to analyze 91 cases of ovarian endometrioid and clear cell carcinomas for the MSI status and the relationship between MSI-H, immune checkpoint molecules, and clinicopathological factors (including patient survival). Only 5 of 91 (5%) cases were MSI-H endometrioid carcinomas. In these cases, CD-8 expression was significantly higher ( = 0.026), confirming an enhanced immune response. From the survival curve, no statistical correlations were found between the MSI-H group and the microsatellite stable (MSS) group; however, the MSS group trended towards better progression-free survival than the MSI-H group ( = 0.056). Patients with PD-L1 expression had shorter overall survival than those without ( = 0.022). Thus, MSI-H is a rare event and not a favorable prognostic factor in ovarian endometrioid and clear cell carcinomas. Thus, to improve the prognosis of ovarian endometrioid carcinoma and clear cell carcinomas, a combination therapy of immune checkpoint inhibitors and other molecular targeted therapies may be required.

摘要

卵巢癌在所有妇科恶性肿瘤中死亡率最高;因此,迫切需要一种新的治疗策略。对于微卫星高度不稳定(MSI-H)的肿瘤,已考虑使用免疫检查点抑制剂。然而,MSI-H肿瘤在卵巢子宫内膜样癌和透明细胞癌中的发生率仍不清楚。在此,采用聚合酶链反应分析了91例卵巢子宫内膜样癌和透明细胞癌的MSI状态以及MSI-H、免疫检查点分子与临床病理因素(包括患者生存率)之间的关系。91例(5%)病例中只有5例为MSI-H子宫内膜样癌。在这些病例中,CD-8表达显著更高(P = 0.026),证实免疫反应增强。从生存曲线来看,MSI-H组与微卫星稳定(MSS)组之间未发现统计学相关性;然而,MSS组的无进展生存期有优于MSI-H组的趋势(P = 0.056)。PD-L1表达阳性的患者总生存期短于无PD-L1表达的患者(P = 0.022)。因此,MSI-H在卵巢子宫内膜样癌和透明细胞癌中是一种罕见事件,并非有利的预后因素。因此,为改善卵巢子宫内膜样癌和透明细胞癌的预后,可能需要免疫检查点抑制剂与其他分子靶向治疗的联合治疗。

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