[Application and clinical significance of TCGA molecular classification in endometrial cancer].

Objective: To explore the application and clinical significance of the cancer genome atlas (TCGA) molecular classification in endometrial cancer (EC). Methods: Sixty-six EC patients collected from December 2018 to March 2021 from Peking University People's Hospital were categorized into four subgroups based on TCGA molecular classification tested by next generation sequencing. The correlation among four molecular subgroups and the clinical-pathological features including prognosis were analyzed. Results: (1) Clinical and pathological features: median age at diagnosis was 56 years (range: 24-78 years). The cases were distributed as follows: 3 (5%) cases DNA polymerase epsilon (POLE) ultra-mutated, 11 (17%) cases high microsatellite instability (MSI-H) including 2 Lynch syndrome, 42 (64%) cases low copy-number (CN-L) and 10 (15%) cases high copy-number (CN-H). There were significant differences among four subtypes in the combination of other tumors, tumor family history, surgical method, International Federation of Gynecology and Obstetrics (FIGO, 2009) stage, depth of muscle invasion and lymph vascular space invasion (all P<0.05). The proportions of patients in CN-H subgroup with advanced FIGO stage (stage Ⅲ-Ⅳ), deep muscle invasion and positive lymph-vascular space invasion were significantly increased. There were no significant differences in age, menopausal status, body mass index, metabolic syndrome-related complications, preoperative serum CA125 and human epididymis protein 4 levels, tumor size, pathological grade (only endometrioid cancer), and lymph node metastasis among the 4 TCGA molecular types (all P>0.05). (2) Immuno-related molecular analysis: among 66 EC patients, 27 patients underwent immunohistochemical analysis of programmed cell death 1 ligand 1 (PD-L1) protein, and 28 patients underwent tumor mutation burden (TMB) detection. POLE and MSI-H subgroups contained TMB than those in CN-L and CN-H (P<0.05).(3) Prognosis: the median follow-up time was 10 months (range: 0-28 months). The progression-free survival rate of TCGA molecular types were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 80% (CN-H) respectively and had significant differences (P=0.034). The overall survival were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 90% (CN-H) respectively, but there were not statistically significant difference (P=0.361). POLE ultra-mutated and MSI-H subgroups had the best survival, while CN-H had the worst. Conclusion: TCGA molecular classification has feasibility and clinical value in clinical application of EC, which is helpful to identify the prognosis of patients.目的： 探讨癌症基因组图谱（TCGA）分子分型在子宫内膜癌（EC）中的应用及其临床意义。 方法： 收集2018年12月至2021年3月于北京大学人民医院行手术治疗且采用高通量测序技术进行TCGA分子分型的EC患者共66例，EC的TCGA分子分型分为4种，DNA聚合酶ε（POLE）超突变型、高度微卫星不稳定性（MSI-H）型、低拷贝型、高拷贝型。回顾性分析4种TCGA分子分型患者的临床病理特征、免疫相关分子学特征以及预后情况。 结果： （1）临床病理特征：66例EC患者的中位年龄为56岁（范围：24~78岁）。其中，POLE超突变型3例（5%），MSI-H型11例（17%，其中Lynch综合征2例），低拷贝型42例（64%），高拷贝型10例（15%）。4种TCGA分子分型患者的合并其他器官恶性肿瘤情况、肿瘤家族史、手术方式、分期、肌层浸润深度、淋巴脉管间隙浸润（LVSI）、病理类型分别比较，差异均有统计学意义（P<0.05），其中高拷贝型患者晚期（Ⅲ~Ⅳ期）、深肌层浸润、LVSI阳性所占比例显著升高；而4种TCGA分子分型患者的年龄、绝经状态、体质指数、代谢综合征相关合并症、术前血清CA125及人附睾蛋白4水平、肿瘤最大径、病理分级（仅指子宫内膜样癌）、淋巴结转移情况分别比较，差异均无统计学意义（P>0.05）。（2）免疫相关分子学特征：66例EC患者中，27例患者行细胞程序性死亡配体1（PD-L1）蛋白免疫组化法检测，28例患者行肿瘤突变负荷（TMB）检测，POLE超突变型及MSI-H型患者的PD-L1阳性表达率、TMB高表达率均显著高于低拷贝型、高拷贝型患者（P<0.05）。（3）预后分析：66例EC患者的中位随访时间为10个月（范围：0~28个月），随访期内死亡2例（低拷贝型1例、高拷贝型1例），盆腔复发和远处转移3例（低拷贝型1例、高拷贝型2例）。POLE超突变型、MSI-H型、低拷贝型、高拷贝型患者的无进展生存率（PFS）分别为100%、100%、98%、80%，4者比较，差异有统计学意义（P=0.034）；总生存率（OS）分别为100%、100%、98%、90%，4者比较，差异无统计学意义（P=0.361）。其中，POLE突变型、MSI-H型患者的PFS、OS较高，高拷贝型患者最低。 结论： EC的TCGA分子分型在临床应用中具有可行性及应用价值，对于EC患者的预后有一定的预测作用，可为患者的个体化诊断和治疗提供新策略。.