子宫内膜癌患者微卫星不稳定性及其临床意义研究

Microsatellite Instability and Its Clinical Significance in Endometrial Carcinoma

背景子宫内膜癌是女性常见恶性肿瘤之一,近年来微卫星不稳定性在子宫内膜癌进展中的作用逐渐受到重视,但关于微卫星不稳定与子宫内膜癌患者临床病理特征及预后的关系研究较少见。目的分析子宫内膜癌患者微卫星不稳定性及其临床意义。方法选取2015年1月至2020年12月在湖北医药学院附属十堰市人民医院进行手术治疗的子宫内膜癌患者248例,收集其癌组织标本,采用免疫组织化学法检测MutL同源物1(MLH1)、MutS同源物2(MSH2)、MutS同源物6(MSH6)、减数分裂后分离蛋白(PMS2)表达情况。分析微卫星不稳定性与子宫内膜癌患者临床病理特征及预后的关系。结果子宫内膜样腺癌患者MLH1、MSH2、MSH6、PMS2表达缺失率分别为32.6%(78/239)、22.2%(53/239)、2.9%(7/239)、65.7%(157/239);子宫内膜鳞癌患者MLH1、MSH2、MSH6、PMS2表达缺失率分别为5/5、3/5、5/5、4/5;子宫内膜透明细胞癌患者MLH1、MSH2、MSH6、PMS2表达缺失率分别为4/4、2/4、3/4、2/4。不同病理类型子宫内膜癌患者MLH1、MSH2、MSH6、PMS2表达缺失率比较,差异有统计学意义(P<0.05)。子宫内膜样腺癌患者高微卫星不稳定性(MSI-H)、低微卫星不稳定性(MSI-L)、微卫星稳定性(MSS)发生频率分别为19.7%(47/239)、34.7%(83/239)、45.6%(109/239);子宫内膜鳞癌患者MSI-H、MSI-L、MSS发生频率分别为4/5、1/5、0;子宫内膜透明细胞癌患者MSI-H、MSI-L、MSS发生频率分别为3/4、1/4、0。不同病理类型子宫内膜癌患者MSI-H、MSI-L、MSS发生频率比较,差异有统计学意义(P<0.05)。不同年龄、肿瘤分化程度子宫内膜癌患者MSI-H、MSI-L、MSS发生频率比较,差异无统计学意义(P>0.05);不同肌层侵犯深度子宫内膜癌患者MSI-H、MSI-L、MSS发生频率比较,差异有统计学意义(P<0.05)。MSI-H、MSI-L、MSS子宫内膜癌患者总生存期、无病生存期的Kaplan-Meier生存曲线比较,差异无统计学意义(P>0.05)。Cox比例风险模型分析结果显示,错配修复蛋白(MMRP)表达情况是子宫内膜癌患者总体生存情况的独立影响因素(P<0.05),但并非无病生存情况的独立影响因素(P>0.05)。结论微卫星不稳定性与子宫内膜癌患者病变进展及预后有关,检测微卫星不稳定性对子宫内膜癌的临床防治有一定参考价值。

Background The role of microsatellite instability in the progression of endometrial cancer,a common cancer in women,has obtained increasing attentions in recent years.However,there are few studies regarding the association of microsatellite instability with clinicopathologic features and prognosis in patients with endometrial cancer.Objective To investigate the microsatellite instability and its clinical significance in patients with endometrial carcinoma.Methods A total of 248 endometrial cancer patients who underwent surgery in Shiyan People's Hospital Affiliated to Hubei University of Medicine from January 2015 to December 2020 were selected.Their cancer tissue specimens were collected to detect the expression of MLH1,MSH2,MSH6 and PMS2 by immunohistochemistry.Relations of microsatellite instability with clinicopathologic features and prognosis were analyzed.Results The rates of lost expression of MLH1,MSH2,MSH6 and PMS2 were 32.6%(78/239),22.2%(53/239),2.9%(7/239)and 65.7%(157/239),respectively,in patients with endometrioid adenocarcinoma.For those with endometrial squamous cell carcinoma,the rates of lost expression of MLH1,MSH2,MSH6 and PMS2 were 5/5,3/5,5/5 and 4/5,respectively.And rates of lost expression of MLH1,MSH2,MSH6 and PMS2 were 4/4,2/4,3/4,and 2/4,respectively,in those with endometrial clear cell carcinoma.The rates of lost expression of MLH1,MSH2,MSH6 and PMS2 varied significantly by the pathological pattern of endometrial carcinoma(P<0.05).The prevalence of high-level microsatellite instability(MSI-H),low-level microsatellite instability(MSI-L)and microsatellite stability(MSS)was 19.7%(47/239),34.7%(83/239)and 45.6%(109/239),respectively,in patients with endometrioid adenocarcinoma.The prevalence of MSI-H,MSI-L and MSS was 4/5,1/5 and 0,respectively,in patients with endometrial squamous cell carcinoma.And that of MSI-H,MSI-L and MSS was 3/4,1/4 and 0,respectively,in patients with endometrial clear cell carcinoma.The prevalence of MSI-H,MSI-L and MSS differed significantly by the pathological pattern of endometrial carcinoma(P<0.05).The prevalence of MSI-H,MSI-L and MSS was associated with the depth of myometrial invasion(P<0.05),but was not associated with age and degree of histologic differentiation of endometrial cancer(P>0.05).There were no significant differences of Kaplan-Meier curves for overall survival and disease-free survival in endometrial cancer patients with MSI-H,MSI-L and MSS(P>0.05).Cox proportional hazards regression analysis results showed that the expression of mismatch repair protein was not the independent influencing factor for disease-free survival(P>0.05),but for overall survival(P<0.05)in patients with endometrial cancer.Conclusion Microsatellite instability is correlated with the progression and prognosis of endometrial cancer,so detecting it may have some referential value for clinical prevention and treatment of endometrial cancer.