MDC1和MMR蛋白在子宫内膜癌中的表达及临床意义

目的探讨DNA损伤检查点蛋白调节子1(MDC1)与错配修复(MMR)蛋白在子宫内膜癌中的表达及其与相关临床特征的关系。方法回顾性分析126例子宫内膜癌患者的临床及病理资料,收集患者手术或刮宫标本进行HE染色和免疫组化染色,检测MDC1、MMR蛋白(MSH6、MSH2、PMS2、MLH1)的表达,并根据MDC1及MMR蛋白免疫组化结果,分析MDC1、MMR蛋白表达及结合两种蛋白不同表达与患者临床特征的关系。采用Kaplan-Meier法绘制生存曲线图分析MDC1和MMR蛋白联合检测与总生存率的关系。采用Spearman秩相关性分析MDC1与MMR蛋白表达的相关性。结果与MDC1阳性表达患者相比,MDC1阴性表达患者年龄较小,主要为低级别(1~2级)子宫内膜样腺癌(P<0.05);与MMR表达完整(MMR-p)患者相比,MMR表达缺失(MMR-d)患者年龄较小,主要为低级别(1~2级)子宫内膜样腺癌(P<0.05)。MDC1阴性表达/MMR-p、MDC1阳性表达/MMR-p、MDC1阴性表达/MMR-d、MDC1阳性表达/MMR-d各组患者年龄、组织学类型、组织学分级比较,差异具有统计学意义(P<0.05);而临床分期、肌层浸润深度比较,差异无统计学意义(P>0.05)。MDC1、MMR蛋白联合检测与患者的总生存率无关(P>0.05),MDC1阴性表达占所有子宫内膜癌患者的9.5%(12/126),与MMR-d呈正相关(P<0.001)。结论MDC1、MMR蛋白多在低级别子宫内膜癌中失表达,并且MDC1阴性表达与MMR-d具有正相关性,提示MDC1失表达与子宫内膜癌的微卫星不稳定性密切相关。

Expressions and clinical significances of MDC1 and MMR proteins in endometrial cancer

Objective To explore the expressions of mediator of DNA damage checkpoint protein 1(MDC1)and mismatch repair(MMR)proteins in endometrial cancer and their relationships with related clinical features.Methods The clinical and pathological data of 126 patients with endometrial cancer were retrospectively analyzed.The surgical or curettage specimens of the patients were collected for HE staining and immunohistochemical staining,and the expressions of MDC1 and MMR proteins including MSH6,MSH2,PMS2 and MLH1 were detected.The expressions of MDC1 and MMR proteins and the relationship between different expressions of the two proteins and the clinical features of patients were analyzed based on the immunohistochemical results of MDC1 and MMR proteins.The Kaplan-Meier method was used to draw a survival curve to analyze the relationship between the combined detection of MDC1 and MMR proteins and overall survival.Spearman rank correlation was used to analyze the correlation between expressions of MDC1 and MMR proteins.Results Compared with patients with MDC1 positive expression,patients with MDC1 negative expression were younger and mainly low-grade(grade 1 to 2)endometrioid adenocarcinoma(P<0.05);compared with MMR-proficient(MMR-p)patients,MMR-deficient(MMR-d)patients were younger and mainly low-grade(grade 1 to 2)endometrioid adenocarcinoma(P<0.05).There were statistically significant differences in the age,histological type and histological classification of patients in the groups of MDC1 negative expression/MMR-p,MDC1 positive expression/MMR-p,MDC1 negative expression/MMR-d and MDC1 positive expression/MMR-d(P<0.05);while there was no statistically significant difference in the clinical staging or the depth of myometrial invasion(P>0.05).The combined detection of MDC1 and MMR proteins had no correlation with the overall survival of patients(P>0.05).MDC1 negative expression accounted for 9.5%(12/126)of all endometrial cancer patients,which had positive correlation with MMR-d(P<0.001).Conclusion MDC1 and MMR proteins are mainly deficient in low-grade endometrial cancer,and MDC1 negative expression and MMR-d have a positive correlation,which suggests that MDC1 deficient is closely related to the microsatellite instability of endometrial cancer.