Objective: To analyze the clinical significance of molecular classification and hereditary phenotype in endometrial carcinoma (EC) based on high throughput sequencing (NGS). Methods: 97 EC samples were collected retrospectively from December 2019 to October 2022 in China-Japan Friendship Hospital. NGS technique was used to analyze the molecular classification, POLE hypermutation, microsatellite high Instability/mismatch repair dysfunction (MSI-H/MMRd), P53 protein abnormality (P53 abn), and non-specific molecular profile (NSMP). Lynch syndrome related genes and BRCA1/2 genes were detected by NGS and their genetic characteristics were analyzed. Results: Of the 97 EC cases, 77 were endometrial adenocarcinoma and 20 were other pathological subtypes. The proportions of the four molecular subtypes were 9.3% (9/97) POLE hypermutation, 16.5% (16/97) MSI-H, 17.5% (17/97) P53 abn and 56.7% (55/97) NSMP, respectively. There were significant differences in age, histological type, lymph node metastasis, pathological stage and other parameters among the four molecular types (P＜0.05). 8.2% (8/97) were multiple molecular typing and four multiple molecular typings detected, including POLEmut-MSI-H, POLEmut-P53abn, MSI-H-P53abn, P53abn-P53abn, which accounted for 1.0% (1/97), 3.1% (3/97), 1.0% (1/97) and 3.1% (3/97), respectively. The consistent rate of MSI-H and MMR protein expression was 92.9% (Kappa=0.818, P＜0.001). The coincidence rate between TP53 gene sequencing and P53 protein expression was 88.9% (Kappa=0.661, P＜0.001). In MSI-H type, 25.0% (4/16) were diagnosed as Lynch syndrome, and 75.0% (12/16) were diagnosed as Lynch like syndrome. 7.2% (7/97) BRCA2 somatic variation was detected, while BRCA1/2 germline variation was not detected in 97 cases. Conclusions: EC molecular classification has feasibility and clinical value. High throughput sequencing can detect low frequency mutations of TP53 gene, suggesting that it can provide more accurate molecular information and more accurate molecular typing effect. It is suggested to further detect Lynch syndrome related genes in patients with MSI-H, so as to carry out genetic management for patients and their families and achieve better therapeutic effect.
目的： 基于高通量测序（NGS）分析子宫内膜癌分子分型的临床病理及遗传分子表型特征。 方法： 回顾性收集2019年12月至2022年10月中日友好医院97例子宫内膜癌样本，采用NGS技术分析POLE突变（mut）型、错配修复功能缺陷型［微卫星高度不稳定/错配修复缺陷型（MSI-H/MMRd）］、P53蛋白异常型（P53 abn）、非特异性分子谱型（NSMP）4种分子分型的临床病理、多重分子表型等特征，进行林奇综合征相关基因及乳腺癌相关基因1/2（BRCA1/2）基因NGS并分析其遗传特征。 结果： 97例子宫内膜癌中，77例为子宫内膜样腺癌，20例为其他病理亚型。4种分子亚型所占比例分别为POLE mut型9.3%（9/97）、MSI-H/MMRd型16.5%（16/97）、P53 abn型17.5%（17/97）、NSMP型56.7%（55/97）。4种分子分型患者的年龄、组织学分型、淋巴结转移、肿瘤分期等参数差异均有统计学意义（均P＜0.05）。8.2%（8/97）的患者为多重分子分型，检测到POLE mut-MSI-H/MMRd、POLE mut-P53 abn、MSI-H/MMRd-P53 abn、P53 abn多位点变异4种多重分子分型，所占比例分别为1.0%（1/97）、3.1%（3/97）、1.0%（1/97）、3.1%（3/97）。MSI-H与错配修复蛋白表达一致率为92.9%（Kappa=0.818，P＜0.001），TP53基因测序与P53蛋白表达一致率为88.9%（Kappa=0.661，P＜0.001）。MSI-H/MMRd型中25.0%（4/16）确诊为林奇综合征，75.0%（12/16）为林奇样综合征。7.2%（7/97）的样本中检测到BRCA2体系变异，97例子宫内膜癌样本中均未检测到BRCA1/2基因胚系变异。 结论： 子宫内膜癌分子分型具有可行性及临床应用价值。NGS可检测到TP53基因低频突变，提示高通量测序能够提供更准确的分子信息，分子分型效果更准确。建议对MSI-H型患者进一步检测林奇综合征相关基因，以便对患者及其家属进行遗传管理，实现更好的治疗效果。.