早期高危子宫内膜癌的分子分型与生存结局：GOG-0249辅助分析
GOG-0249试验中315例I-II期高危/高危中间危子宫内膜癌患者按免疫组化分为p53abn（23.5%）、dMMR（32.1%）和p53wt（44.4%）。p53abn和dMMR患者5年RFS和OS均显著差于p53wt；但分子亚组间阴道近距离放疗加化疗与盆腔放疗的RFS和OS无差异。
要点
- p53abn子宫内膜癌5年RFS 58.7%、OS 70.7%，预后最差。
- dMMR患者5年RFS 74.4%、OS 84.3%，也差于p53wt。
- 分子亚组不能预测阴道近距离放疗加化疗对比盆腔放疗的获益。
核心结论
- 分子分型对I-II期高危/高危中间危子宫内膜癌的生存结局有预后价值。
- p53abn癌症患者复发和死亡风险最高。
- 分子亚组似乎不能预测阴道近距离放疗加化疗对比盆腔放疗的获益。
研究设计与样本
- GOG-0249试验的辅助分析，纳入601例高危中间危早期子宫内膜癌患者随机接受阴道近距离放疗加化疗（卡铂/紫杉醇3周期）或盆腔放疗。
- 315例患者通过免疫组化确定分子亚组：dMMR、p53wt、p53abn。
- 采用Kaplan-Meier曲线和Cox比例风险模型分析5年RFS和OS，调整淋巴结清扫、计划阴道近距离放疗和治疗组。
主要发现
- 315例中p53abn占23.5%，dMMR占32.1%，p53wt占44.4%。
- p53abn与年龄较大（p=0.004）、浆液性组织学（p<0.001）、淋巴结清扫（p=0.02）和计划阴道近距离放疗（p<0.001）相关。
- p53abn患者5年RFS 58.7%［HR=4.0（95%CI：2.1-7.5）］、OS 70.7%［HR=9.4（95%CI：3.8-23.6）］，dMMR患者5年RFS 74.4%［HR=1.8（95%CI：0.9-3.3）］、OS 84.3%［HR=3.0（95%CI：1.2-7.8）］，均差于p53wt（83.4%和95.3%）（p<0.001）。
- 分子亚组内RFS（p=0.7）和OS（p=0.8）按治疗分组无差异。
临床怎么用
- 对早期高危/高危中间危子宫内膜癌应常规行MMR和p53免疫组化分子分型以评估预后。
- p53abn和dMMR患者预后较差，需考虑新型治疗策略。
- 分子分型目前不能指导选择阴道近距离放疗加化疗或盆腔放疗。
局限性
- 为GOG-0249试验的辅助分析，仅315例患者有分子分型数据。
- 分子分型仅基于免疫组化，未行测序验证。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
OBJECTIVE: Determine whether mismatch repair (MMR) and p53 expression predict recurrence-free survival (RFS) and overall survival (OS) in early-stage endometrial cancer (EC) patients treated with vaginal cuff brachytherapy plus chemotherapy (VCB/C) versus pelvic radiation therapy (RT). METHODS: In the GOG-0249 trial, 601 patients with high-intermediate risk (HIR) early-stage EC were randomized to VCB/C (carboplatin/paclitaxel for 3 cycles) or pelvic RT. Molecular subgroups, deficient MMR (dMMR), p53 wildtype (p53wt), p53 abnormal (p53abn), were determined by immunohistochemistry. Five-year RFS and OS were analyzed using Kaplan-Meier curves and Cox proportional hazards models, adjusting for lymphadenectomy, planned VCB, and treatment group. RESULTS: Among 315 patients, 23.5% had EC exhibiting p53abn expression, 32.1% had dMMR, and 44.4% had p53wt. p53abn EC was associated with older age (p = 0.004), serous histology (p < 0.001), lymphadenectomy (p = 0.02), and planned VCB (p < 0.001). Five-year RFS and OS were worse in patients with p53abn cancers, 58.7% [Hazard Ratio (HR) = 4.0 (95% Confidence Interval (CI): 2.1-7.5)] and 70.7% [HR = 9.4 (95%CI: 3.8-23.6)] and dMMR cancers 74.4% [HR = 1.8 (95%CI: 0.9-3.3)] and 84.3% [HR = 3.0 (95%CI: 1.2-7.8)] compared to those with p53wt (referent) (83.4% and 95.3%) (p < 0.001). The RFS (p = 0.7) and OS (p = 0.8) rates did not differ by treatment within molecular subgroups. CONCLUSION: Molecular classification is prognostic for survival outcomes in patients with stage I-II HIR/high-risk EC. Patients with p53abn cancers seem to have the highest risk of relapse and death. Molecular subgroups do not appear to predict benefit from VCB/C as compared to pelvic RT. Novel therapeutic approaches are needed, especially for those with dMMR and p53abn expressing cancers.
引用
- Kuroki LM, Enserro DM, Lankes HA, et al. Molecular classification and association with survival outcomes in high-intermediate and high-risk early-stage endometrial cancers: Ancillary analysis of GOG-0249. Gynecol Oncol. 2026. PMID: 42190623. doi:10.1016/j.ygyno.2026.05.013
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。