错配修复蛋白在子宫内膜癌中的表达及临床意义

发布时间：2018-04-13 19:53

本文选题：Lynch综合征 + 子宫内膜癌　；参考：《山西医科大学》2017年硕士论文

【摘要】：目的:1.通过检测错配修复(mismatch repair,MMR)蛋白在子宫内膜癌中的表达情况,筛选可疑的Lynch综合征(Lynch syndrome,LS)相关子宫内膜癌,并结合临床病理特征分析山西地区LS相关子宫内膜癌的发病特点。2.了解MLH1蛋白缺失的子宫内膜癌中MLH1基因启动子甲基化状态。方法:1.运用免疫组化技术检测错配修复蛋白MSH2、MSH6、MLH1和PMS2在443例子宫内膜癌中的表达情况。2.应用甲基化特异性PCR(MSP)检测MLH1蛋白缺失(MLH1/PMS2蛋白缺失)子宫内膜癌癌组织MLH1基因启动子甲基化状态。结果:4种蛋白同时表达为散发性子宫内膜癌,一种或多种蛋白缺失为可疑的LS相关子宫内膜癌。1.443例子宫内膜癌中,115例(26%)出现MMR蛋白表达缺失,其中MLH1/PMS2、MSH2/MSH6、MSH6、PMS2和MSH6/MLH1/PMS2缺失率分别为42%、23%、17%、17%和3%,为可疑的LS相关子宫内膜癌。2.与散发癌组相比,可疑的LS相关子宫内膜癌组中,无肥胖(BMI28 kg/m2)(p=0.04)、高级别肿瘤(p=0.012)、曾经或同时发生其他部位肿瘤(p=0.009)更常见;年龄,高血压、糖尿病病史,家族肿瘤史,组织学类型,肿瘤部位,FIGO分期,肌层浸润,淋巴结转移,淋巴管、血管浸润等临床病理特征无显著性差异(p0.05)。3.各MMR蛋白缺失组中,MSH6和PMS2蛋白缺失组中,高级别肿瘤更常见(p=0.000)。4.与散发癌相比,MSH2/MSH6缺失组中BMI28 Kg/m2和具有家族肿瘤病史患者更常见;MSH6和PMS2缺失组中,高级别肿瘤更多见(p0.05)。5.检测48例MLH1蛋白缺失子宫内膜癌的癌组织中MLH1基因启动子甲基化状态,因为标本组织提取DNA量不足或质量不达标,获得满意结果14例,14例癌组织均存在MLH1基因启动子甲基化。结论:1.山西地区可疑LS相关子宫内膜癌约占全部子宫内膜癌病例的26%。2.有异时肿瘤病史或同时发生其它部位肿瘤的EC患者,应高度警惕LS的发生。3.与散发性相比,LS相关子宫内膜癌无肥胖、高级别的患者更常见。4.MLH1基因启动子甲基化是MLH1基因常见的失活方式。
[Abstract]:Purpose 1.By detecting the expression of mismatch repairn MMRs protein in endometrial carcinoma, the suspected Lynch syndrome syndrome-associated endometrial carcinoma was screened, and the pathogenetic characteristics of LS associated endometrial carcinoma in Shanxi area were analyzed.To investigate the methylation status of MLH1 promoter in endometrial carcinoma without MLH1 protein.Method 1: 1.Immunohistochemical technique was used to detect the expression of mismatch repair protein MSH2, MSH6, MLH1 and PMS2 in 443 cases of endometrial carcinoma.The methylation status of MLH1 gene promoter in endometrial carcinoma tissues was detected by methylation specific PCR- MSPs (MLH1 protein deletion / MLH1 / PMS2 deletion).Results one or more of the 4 proteins were expressed in sporadic endometrial carcinoma, and the loss of one or more proteins was suspected in LS-associated endometrial carcinoma. There was a loss of MMR protein in 115 cases of endometrial carcinoma in 1. 443 cases.The deletion rate of MLH1 / PMS2 / MSH2 / MSH6 + MSH6 + PMS2 and MSH6/MLH1/PMS2 were 42% and 23 17%, respectively, and 3% and 3%, respectively, which were suspected LS-associated endometrial carcinoma.In the suspected LS-associated endometrial carcinoma group, BMI28 kg / m2p0. 04%, high grade tumor p0. 012, which had or occurred at the same time, were more common; age, hypertension, diabetes history, family tumor history, histological type.Figo stage, myometrial invasion, lymph node metastasis, lymphatic vessel invasion and vascular infiltration were not significantly different in the clinicopathological features of tumor site.In all MMR deletion groups, the high grade tumors were more common in MSH6 and PMS2 deletion groups.BMI28 Kg/m2 was more common in MSH2 / MSH6 deletion group than that in sporadic cancer group, and in patients with family history of cancer, high grade tumors were more common in MSH6 and PMS2 deletion groups.The methylation status of MLH1 gene promoter was detected in 48 cases of endometrial carcinoma with MLH1 protein deletion. The methylation of MLH1 gene promoter was found in 14 cases of endometrial carcinoma with satisfactory results because the quantity of DNA extracted from the samples was insufficient or the quality was not up to standard.Conclusion 1.Suspected LS associated endometrial carcinoma accounts for 26. 2% of all endometrial cancer cases in Shanxi.EC patients with abnormal tumor history or other tumors at the same time should be on high alert for LS. 3.LS-associated endometrial carcinoma is not obese compared with sporadic. Methylation of MLH1 gene promoter is more common in high grade patients than in sporadic endometrial carcinoma. MLH1 promoter methylation is a common inactivation mode of MLH1 gene.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33

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