子宫内膜样癌123例错配修复蛋白状态的临床分析

Mismatch repair protein profiles and clinicopathological features in endometrial endometrioid carcinoma: a retrospective analysis in 123 patients

目的将癌症基因组图谱(TCGA)定义的子宫内膜样癌(EEC)分子分型与实际工作结合,为EEC分子分型在临床实际工作的应用提供理论依据。方法选取123例病理诊断明确为EEC的术后标本,用错配修复(MMR)蛋白和P53蛋白免疫组织化学对微卫星不稳定性及TP53突变情况进行初筛,对临床病理参数与MMR蛋白、TP53突变情况进行关联性分析。结果123例EEC患者中78例错配修复正常(p MMR)、32例为错配修复缺陷(dMMR),另有13例存在TP53突变。国际妇产科学联合会(FIGO)分级为高级别患者TP53突变比例更高,Ki-67≥40%的病例多见于TP53突变组;而FIGO分级为低级别患者pMMR比例更高(P<0.01)。dMMR组32例患者中4例进行了微卫星不稳定性(MSI)二代测序(NGS)或聚合酶链反应(PCR)检测,3例NGS结果为高度微卫星不稳定(MSI-H),1例同时进行了PCR检测及NGS检测,PCR结果为微卫星稳定(MSS),NGS结果为MSI-H。结论最新的EEC分子分型应用于临床病理工作,可以为患者提供较为精准的病理信息。

Objective To integrate the molecular typing of endometrial endometrioid carcinoma(EEC)as classified by the Cancer Genome Atlas(TCGA)database in our daily work,and to lay a theoretical foundation for the use of EEC molecular typing in clinical practice.Methods Postoperative specimens were obtained from 123 patients who were pathologically confirmed to have EEC,and were subjected to a preliminary screening for mi-crosatellite instability and TP53 mutation by immunohistochemical assay of mismatch repair protein(MMR)and p53 protein.The correlation between clinicopathology,MMR profiles and TP53 mutation was analyzed.Results Of the 123 EEC patients,78 patients showed mismatch repair protein proficiency(pMMR),32 patients showed mismatch repair protein deficiency(dMMR),and the other 13 patients had TP53 mutations.The patients were as-signed to 3 groups accord-ing to these scenarios.TP53 mutations were more likely to occur in patients with higher FIGO grades.TP53-mu-tated patients were more likely to have level of Ki-67≥40%.Patients with lower FIGO grades more likely showed pMMR(P<0.01).Of the 32 patients in the dMMR group,4 patients underwent next-generation sequencing(NGS)or poly-merase chain reaction(PCR)microsatellite instability(MSI);three of them showed high microsatellite instability(MSI-H)on NGS,whereas one who underwent both PCR and NGS showed microsatellite stability(MSS)on PCR and MSI-H on NGS.Conclusion Pathological study of EEC currently in use may help more effectively integrate the latest developed EEC molecular typing in practice of clinical pathology and provide more precise pathological information for the patients.