分子和病理数据指导子宫内膜样子宫内膜癌患者选择卵巢保留。
Molecular and pathologic data to guide selection of patients with endometrioid endometrial cancer for ovarian preservation.
机构信息
Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
出版信息
Int J Gynecol Cancer. 2024 May 6;34(5):697-704. doi: 10.1136/ijgc-2023-005194.
OBJECTIVES
To investigate the association of molecular and pathologic factors with concurrent or recurrent ovarian disease to guide ovarian preservation in endometrioid endometrial cancer.
METHODS
Patients with endometrial cancer ≤50 years of age at diagnosis were grouped by elective oophorectomy versus ovarian preservation at staging (January 2010 to June 2021). Tumors were stratified by molecular sub-type and mutational status with next generation sequencing and immunohistochemistry. Germline data identified patients with Lynch syndrome. Associations between molecular/pathologic features and concurrent ovarian disease in patients electing oophorectomy were compared with the Wilcoxon rank-sum and Fisher's exact tests. Associations with isolated ovarian recurrences in patients who chose ovarian preservation were examined using survival analyses.
RESULTS
Among 317 patients with endometrial cancer who underwent bilateral oophorectomy, 27 (9%) had malignant ovarian tumors, of whom 11 (41%) had no gross ovarian involvement on intra-operative survey. For patients with sequencing, concurrent malignant ovarian tumors were diagnosed in 0/14 (0%) , 2/48 (4%) copy number-low/no specific molecular profile, 10/22 (45%) microsatellite instability-high, and 3/6 (50%) copy number-high/abnormal patients (p<0.001). Concurrent malignant ovarian tumors were present in 1/30 (3%) hotspot -mutated versus 10/60 (17%) wildtype/ non-hotspot mutated endometrial cancer patients (p=0.11) and 7/28 (25%) Lynch versus 7/74 (9%) non-Lynch syndrome patients (p=0.06). Concurrent malignant ovarian tumors were present in patients with higher grade endometrial cancer (5% grade 1 vs 20% grade 2 and 24% grade 3; p<0.001), present versus absent lymphovascular space invasion (20% vs 6%; p=0.004), positive versus negative pelvic washings (28% vs 7%; p=0.016), and ≥50% versus <50% myoinvasion (24% vs 7%; p=0.004). Of 103 patients who chose ovarian preservation, four had isolated ovarian recurrences (two had high-risk pathologic features and two had high-risk molecular features).
CONCLUSIONS
The integration of molecular and pathologic data may improve risk stratification of pre-menopausal patients with endometrial cancer and enhance candidate selection for ovarian preservation.
目的
探讨分子和病理因素与同时性或复发性卵巢疾病的关系，以指导子宫内膜样腺癌患者的卵巢保留。
方法
根据在分期时是否选择择期卵巢切除术（2010 年 1 月至 2021 年 6 月）将诊断时年龄≤50 岁的子宫内膜癌患者分为两组。通过下一代测序和免疫组织化学对肿瘤进行分子亚型和突变状态分层。种系数据确定了林奇综合征患者。在选择卵巢切除术的患者中，比较了分子/病理特征与同时性卵巢疾病的关系，采用 Wilcoxon 秩和检验和 Fisher 确切检验。在选择卵巢保留的患者中，通过生存分析检查与孤立性卵巢复发的关系。
结果
在 317 例行双侧卵巢切除术的子宫内膜癌患者中，27 例（9%）患有恶性卵巢肿瘤，其中 11 例（41%）术中探查未见卵巢明显受累。对于有测序的患者，同时性恶性卵巢肿瘤在 0/14（0%）、2/48（4%）拷贝数低/无特定分子谱、22/22（45%）微卫星不稳定高和 6/6（50%）拷贝数高/异常患者中诊断（p<0.001）。在 30 例（3%）热点突变患者中发现同时性恶性卵巢肿瘤，而在 60 例（17%）野生型/非热点突变子宫内膜癌患者中发现 10 例（p=0.11），在 28 例（25%）林奇综合征患者中发现 7 例，而在 74 例（9%）非林奇综合征患者中发现 7 例（p=0.06）。在高级别子宫内膜癌患者中发现同时性恶性卵巢肿瘤（5%的 1 级 vs. 20%的 2 级和 24%的 3 级；p<0.001）、存在与不存在脉管内肿瘤侵犯（20% vs. 6%；p=0.004）、盆腔冲洗阳性与阴性（28% vs. 7%；p=0.016）和肌层浸润≥50%与<50%（24% vs. 7%；p=0.004）。在选择卵巢保留的 103 例患者中，4 例出现孤立性卵巢复发（2 例具有高危病理特征，2 例具有高危分子特征）。
结论
分子和病理数据的整合可能会改善绝经前子宫内膜癌患者的风险分层，并增强卵巢保留的候选者选择。
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