子宫内膜样癌分子分型的临床病理意义

Clinicopathological significance of molecular classification in endometrioid carcinoma

目的探讨子宫内膜样癌分子分型的临床病理意义。方法收集145例子宫内膜样癌根治手术石蜡标本,应用测序法检测POLE突变,有突变的归为POLE突变型;应用免疫组化方法检测四种错配修复(mismatch repair,MMR)蛋白MLH1、PMS2、MSH2、MSH6和p53蛋白的表达,MMR表达缺失者归为MMR缺陷型(MMR-D);剩余标本根据p53免疫组化结果分为p53突变型和p53野生型。结果145例子宫内膜样癌中,POLE突变型6例(4.1%),MMR-D型44例(30.3%),p53突变型15例(10.3%),p53野生型80例(55.2%)。POLE突变与患者年龄、分化程度、浸润深度、宫颈浸润和淋巴结转移无关(P>0.05);MMR-D与患者年龄相关,与分化程度、浸润深度、宫颈浸润和淋巴结转移无关(P>0.05);p53蛋白异常表达与患者年龄、浸润深度、有无宫颈浸润无关(P>0.05),与肿瘤分化程度、淋巴结转移有关(P<0.05)。结论临床工作中可根据POLE突变检测、MMR蛋白和p53蛋白表达对子宫内膜样癌进行分子分型,为后续治疗选择和预后判断提供指导。

Objective To investigate the clinical and pathological significance of molecular classification in endometrioid carcinoma.Methods A total of 145 paraffin-embedded surgical specimens with endometrioid carcinoma were sequenced to identify POLE mutations,and those with mutations were classified as POLE mutant subgroup;Immunohistochemistry was used to detect the expression of mismatch repair(MMR)proteins including MLH1,PMS2,MSH2 and MSH6 as well as the expression of p53 protein.The loss of MMR protein expression was classified as MMR-deficient(MMR-D)subgroup.The rest cases were divided into p53 mutant type and p53 wild type according to the result of p53 immunohistochemistry.Results Among 145 cases of endometrioid carcinoma,6 cases(4.1%)were classified into POLE mutant group,44 cases(30.3%)MMR-D group,15 cases(10.3%)p53 mutant group and 80 cases(55.2%)p53 wild group,respectively.POLE mutation was not related to the patients’age,degree of differentiation,cervical invasion,depth of invasion,and lymph node metastasis(P>0.05);MMR-D was related to age but not degree of differentiation,cervical invasion,depth of invasion,and lymph node metastasis(P>0.05);p53 abnormal expression was not related to the patients’age,depth of invasion and cervical invasion(P>0.05)but related to the degree of differentiation and lymph node metastasis(P<0.05).Conclusion In clinical work,POLE mutation,MMR-D and p53 mutant group can be screened for molecular classification,which can provide guidance for subsequent treatment selection and prognosis judgment.