Department of Obstetrics and Gynecology, Division of Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Department of Gynecology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Int J Gynecol Cancer. 2024 Oct 7;34(10):1561-1569. doi: 10.1136/ijgc-2024-005672.
To assess the distribution of molecular classes and their impact on the risk of recurrence in endometrial cancer patients with lymph node metastasis at the time of primary surgery.
Endometrial cancer patients with lymph node micrometastasis or macrometastasis (International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIIC) after surgical staging at five referral centers worldwide from October 2013 to September 2022 who underwent molecular classification were identified. Endometrial cancers were categorized into four molecular classes: POLE mutated, mismatch repair deficient, p53 abnormal, and no specific molecular profile. Survival analyses using Kaplan-Meier and Cox models (univariate and multivariate) were conducted to evaluate the relationship between molecular class and 5-year recurrence free survival.
131 patients were included: 55 (42.0%) no specific molecular profile, 46 (35.1%) mismatch repair deficient, 1 (0.8%) POLE mutated, and 29 (22.1%) p53 abnormal. During a 5 year follow-up period, 50 (38.2%) patients experienced a recurrence with a median time of 1.2 years (interquartile range (IQR) 0.5-1.8). Median follow-up for the remaining 81 patients was 3.1 years (IQR 1.3-4.5). Survival analysis revealed a significant difference in recurrence-free survival between no specific molecular profile, mismatch repair deficient, and p53 abnormal classes (log rank p<0.01). In a model adjusted for type of lymph node metastasis and tumor grade, the molecular class did not retain significance (p=0.13), while in a model adjusted for type of lymph node metastasis and adjuvant therapy, the molecular class retained significance (p<0.01).
Among patients with stage IIIC endometrial cancer, POLE mutated tumors exhibited an extremely low prevalence, with no specific molecular profile emerging as the largest molecular subgroup. Despite the significant difference in recurrence-free survival between molecular classes, conventional histopathologic parameters retained crucial prognostic value. Our findings highlight the necessity of integrating molecular classes with pathological characteristics, rather than considering them in isolation as crucial prognostic factors in stage IIIC endometrial cancer.
评估分子亚型的分布及其对原发性手术时有淋巴结转移的子宫内膜癌患者复发风险的影响。
在全球五个转诊中心，从 2013 年 10 月至 2022 年 9 月，对手术分期后有淋巴结微转移或宏观转移（国际妇产科联合会（FIGO）2009 期 III 期）的子宫内膜癌患者进行了分子分类。将子宫内膜癌分为四个分子亚型：错配修复缺陷、POLE 突变、p53 异常和无特定分子特征。使用 Kaplan-Meier 和 Cox 模型（单变量和多变量）进行生存分析，以评估分子亚型与 5 年无复发生存率之间的关系。
共纳入 131 例患者：55 例（42.0%）无特定分子特征，46 例（35.1%）错配修复缺陷，1 例（0.8%）POLE 突变，29 例（22.1%）p53 异常。在 5 年的随访期间，50 例（38.2%）患者发生复发，中位时间为 1.2 年（四分位距（IQR）0.5-1.8）。其余 81 例患者的中位随访时间为 3.1 年（IQR 1.3-4.5）。生存分析显示，无特定分子特征、错配修复缺陷和 p53 异常组之间的无复发生存率有显著差异（对数秩检验，p<0.01）。在调整淋巴结转移类型和肿瘤分级的模型中，分子类型无统计学意义（p=0.13），而在调整淋巴结转移类型和辅助治疗的模型中，分子类型具有统计学意义（p<0.01）。
在 IIIC 期子宫内膜癌患者中，POLE 突变肿瘤的患病率极低，无特定分子特征是最大的分子亚组。尽管分子亚型之间无复发生存率有显著差异，但传统的组织病理学参数仍具有重要的预后价值。我们的研究结果强调了在 IIIC 期子宫内膜癌中，将分子类型与病理特征相结合的必要性，而不是将其视为孤立的关键预后因素。
