Kuang Wei, Zeng Jing, Tong Lingling, Liu Qianqi, Sun Huanxin, Feng Min, Liang Dongni, Wang Wei, Wang Cheng
Department of Pathology, West China Second University Hospital of Sichuan University, Chengdu, Sichuan, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Chengdu, Sichuan, China.
Front Immunol. 2025 May 9;16:1567824. doi: 10.3389/fimmu.2025.1567824. eCollection 2025.
OBJECTIVE: This study evaluated the incidence of Microsatellite Instability-High (MSI-H) in patients with gynecologic cancers in a single gynecologic center and investigated the effect of immune checkpoint inhibitors (ICIs) in treating MSI-H in advanced or recurrent gynecologic cancers. METHODS: We conducted a retrospective study of patients diagnosed with gynecological cancers between June 2021 and May 2024. We investigated their clinicopathological information, the results of microsatellite instability (MSI), the immunohistochemistry staining PD-L1 analyses, the molecular classification testing, and the tumor response to treatment with ICIs. RESULTS: Among 1333 patients included in the analysis, the frequency of MSI-H was 1.3% (3/223) in cervical cancer, 25.7% (280/1091) in endometrial cancer, and 10.5% (2/19) in ovarian or tubal and peritoneal cancer. When the patients were evaluated by histologic type, the frequency of MSI-H was 26.1% (241/921) in endometrioid adenocarcinoma and 35.1% (20/57) in mixed adenocarcinoma. Molecular classification results for the 1020 cases that successfully underwent the tests were 71 for the POLE mutation (POLEmut) subtype, 271 for MMR-deficiency (MMRd) subtype, 571 for the non-specific molecular profile (NSMP) subtype, and 107 for the p53 abnormality (p53abn) subtype. Thirty-five patients were treated with ICIs for at least one cycle. The objective response rate (ORR) was 34.3% (95% CI, 19.1% to 52.2%). Among the patients who achieved an objective response, the median time to respond was 2.65 months, and the median duration of response had not been reached. The median progression-free survival (PFS) was 9 months (95% CI, 4 to 10), and the median overall survival (OS) had not been reached. Additionally, in the patients with endometrial cancer, the median PFS in MSI-H patients was 5 months versus 3 months in microsatellite stable (MSS) patients (Δ = 2 months; p=0.92), and the median OS in both MSI-H and MSS patients had not been reached (p=0.89). CONCLUSION: This study had shown the MSI-H frequencies for the three major types of gynecological tumors and demonstrated the clinical benefit of treatment with ICIs in patients with advanced or recurrent gynecologic cancer. Among endometrial cancer patients, the effects of immunotherapy may be consistent regardless of MSI status.
目的：本研究评估了单个妇科中心妇科癌症患者中微卫星高度不稳定（MSI-H）的发生率，并探讨了免疫检查点抑制剂（ICI）治疗晚期或复发性妇科癌症中MSI-H的效果。 方法：我们对2021年6月至2024年5月期间诊断为妇科癌症的患者进行了一项回顾性研究。我们调查了他们的临床病理信息、微卫星不稳定（MSI）结果、免疫组化染色PD-L1分析、分子分类检测以及肿瘤对ICI治疗的反应。 结果：在纳入分析的1333例患者中，宫颈癌中MSI-H的频率为1.3%（3/223），子宫内膜癌中为25.7%（280/1091），卵巢或输卵管及腹膜癌中为10.5%（2/19）。按组织学类型评估患者时，子宫内膜样腺癌中MSI-H的频率为26.1%（241/921），混合性腺癌中为35.1%（20/57）。成功接受检测的1020例病例的分子分类结果为：POLE突变（POLEmut）亚型71例，错配修复缺陷（MMRd）亚型271例，非特异性分子谱（NSMP）亚型571例，p53异常（p53abn）亚型107例。35例患者接受了至少一个周期的ICI治疗。客观缓解率（ORR）为34.3%（95%CI，19.1%至52.2%）。在达到客观缓解的患者中，中位缓解时间为2.65个月，中位缓解持续时间尚未达到。中位无进展生存期（PFS）为9个月（95%CI，4至10），中位总生存期（OS）尚未达到。此外，在子宫内膜癌患者中，MSI-H患者的中位PFS为5个月，而微卫星稳定（MSS）患者为3个月（差值=2个月；p=0.92），MSI-H和MSS患者的中位OS均未达到（p=0.89）。 结论：本研究显示了三种主要类型妇科肿瘤的MSI-H频率，并证明了ICI治疗晚期或复发性妇科癌症患者的临床益处。在子宫内膜癌患者中，无论MSI状态如何，免疫治疗的效果可能是一致的。
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