【摘要】 目的探讨错配修复(MMR)蛋白、抑癌基因(p53)及程序性死亡蛋白配体1(PD-L1)在子宫内膜癌(EC)中的表达情况,并分析简化的MMR/p53分子分型与EC的临床病理特征以及PD-L1表达的关系。方法选取2015至2018年在湖州市妇幼保健院确诊为EC的患者78例,采用免疫组化En Vision二步法检测EC组织MMR蛋白,包括Mut L同源蛋白1(MLH1)、Mut S同源蛋白2(MSH2)、Mut S同源蛋白6(MSH6)、减数分裂后分离蛋白2(PMS2)4种以及p53、PD-L1的表达并分析其临床意义。结果 EC组织中,MMR缺失率为23.07%(18/78),p53突变率为26.29%(21/78)。MMR蛋白缺失型表达率与患者年龄、病理类型、FIGO分期、肌层浸润深度、脉管浸润情况及淋巴结转移均无关(均P>0.05)。p53突变型表达率与患者年龄、病理类型、FIGO分期、脉管浸润情况及淋巴结转移均有关(均P<0.05),与肌层浸润深度无关(P>0.05)。PD-L1在p53突变型患者中的阳性表达率高于野生型患者(P<0.05),而在MMR缺失型/完整型中阳性表达率无统计学差异(P>0.05)。PD-L1阳性表达率在MMR缺失型且p53突变型组、MMR缺失型且p53野生型组、MMR完整型且p53突变型组及MMR完整型且p53野生型组的表达差异有统计学意义(P<0.05),其中在MMR缺失型且p53突变型组表达率最高,达100%。结论 p53蛋白对EC的预后及分型的具有重要意义,MMR蛋白检测可为EC患者进行遗传性非息肉病性结直肠癌分流提供依据。PD-L1在MMR缺失型且p53突变型患者表达,提示免疫治疗可能使该分子亚型患者受益。更多还原

【Abstract】 Objective To investigate the expression of mismatch repair(MMR) protein, oncosuppressor gene p53 and programmed death protein1(PD-L1) in endometrial carcinoma(EC) and its clinicopathological significance. Methods Theexpression of MMR(including MLH1, MSH2, MSH6, PMS2), p53, and PD-L1 in 78 samples of EC collected in the Pathology Department of Huzhou Maternal and Child Health Hospital from 2015 to 2018 were detected by immunohistochemical En Vision assay. Results The positive expression rates of MMR and p53 in EC were 23.07%(18/78) and 26.29%(21/78). The expression of MMR did not show any statistical correlation with age, pathological type, FIGO stage, depth of infiltration, vascular infiltration and lymph node metastasis(P >0.05). The expression p53 was correlated with the age, pathological type, FIGO stage, vascular infiltration and lymph node metastasis(P<0.05), but not with the depth of infiltration(P >0.05). The positive expression rate of PD-L1 in EC with mutated p53 was higher than that in EC with wild-type p53, and there was no significant difference in PD-1 expression between EC with MMR deficiency and EC without MMR deficiency(P >0.05). There were significant differences in expression of PD-L1 among EC with MMR and p53 both normal, both abnormal and one abnormal(P >0.05), and the expression rate of PD-L1 in EC with MMR deficiency and mutated p53 was the highest(up to 100%). Conclusion The study shows that PD-L1 is highly expressed in endometrial cancer patients with from MMR deficiency and mutated p53, suggesting that immunotherapy may be beneficial to patients with this molecular subtype.更多还原