子宫内膜透明细胞癌分子分型临床应用及其与PD-L1表达的关系

Clinical application of molecular-based classification in endometrial clear cell carcinoma and its relationship with PD-L1 expression

目的探讨子宫内膜透明细胞癌(endometrial clear cell carcinoma,ECCC)分子分型的临床应用及其与PD-L1表达的关系。方法应用测序法检测15例ECCC根治手术标本中POLE突变情况,有突变者为POLE突变型;应用免疫组化法检测错配修复(mismatch repair,MMR)MLH1、MSH2、MSH6、PMS2蛋白表达,有表达缺失者为错配修复缺陷(mismatch repair-deficiency,MMR-D);免疫组化检测p53表达,将其分为p53突变型和p53野生型。应用免疫组化法检测PD-L1蛋白表达,比较不同分子分型的组间差异。结果15例ECCC中POLE突变型0例,MMR-D为5例,p53突变型5例,p53野生型5例。5例MMR-D者PD-L1均阳性。结论ECCC具有分子异质性,部分与子宫内膜样癌相似,部分与浆液性癌相似。PD-L1可以作为ECCC免疫治疗的重要靶标。

Purpose To explore the clinical application of molecular classification on endometrial clear cell carcinoma(ECCC)and its relationship with PD-L1 expression.Methods Fifteen cases of ECCC with radical surgical specimens were sequenced to identify POLE mutations,and those with the mutations were classified as POLE mutant subgroup.Immunohistochemistry was used to detect mismatch repair(MMR)protein including MLH1,MSH2,MSH6,and PMS2 to classify mismatch repair-deficiency(MMR-D)subgroup.According to the results of p53 immunohistochemistry,the rest cases were classified as p53 mutant and p53 wild types.Finally,immunohistochemical method was used to detect PD-L1 protein expression and the differences between different molecular subgroups were compared.Results Among 15 cases of ECCC,no POLE mutation was detected,while 5 cases of MMR-D,5 cases of p53 mutation,and 5 cases of p53 wild type were identified.All 5 cases of MMR-D ECCC had positive expression of PD-L1.Conclusion ECCC has molecular heterogeneity:some cases are biologically similar to endometrioid carcinoma while some are similar to serous carcinomas.PD-L1 can be an important target for ECCC immunotherapy.