本文選題：Lynch綜合征 + 子宮內(nèi)膜癌　； 參考：《山西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:1.通過(guò)檢測(cè)錯(cuò)配修復(fù)(mismatch repair,MMR)蛋白在子宮內(nèi)膜癌中的表達(dá)情況,篩選可疑的Lynch綜合征(Lynch syndrome,LS)相關(guān)子宮內(nèi)膜癌,并結(jié)合臨床病理特征分析山西地區(qū)LS相關(guān)子宮內(nèi)膜癌的發(fā)病特點(diǎn)。2.了解MLH1蛋白缺失的子宮內(nèi)膜癌中MLH1基因啟動(dòng)子甲基化狀態(tài)。方法:1.運(yùn)用免疫組化技術(shù)檢測(cè)錯(cuò)配修復(fù)蛋白MSH2、MSH6、MLH1和PMS2在443例子宮內(nèi)膜癌中的表達(dá)情況。2.應(yīng)用甲基化特異性PCR(MSP)檢測(cè)MLH1蛋白缺失(MLH1/PMS2蛋白缺失)子宮內(nèi)膜癌癌組織MLH1基因啟動(dòng)子甲基化狀態(tài)。結(jié)果:4種蛋白同時(shí)表達(dá)為散發(fā)性子宮內(nèi)膜癌,一種或多種蛋白缺失為可疑的LS相關(guān)子宮內(nèi)膜癌。1.443例子宮內(nèi)膜癌中,115例(26%)出現(xiàn)MMR蛋白表達(dá)缺失,其中MLH1/PMS2、MSH2/MSH6、MSH6、PMS2和MSH6/MLH1/PMS2缺失率分別為42%、23%、17%、17%和3%,為可疑的LS相關(guān)子宮內(nèi)膜癌。2.與散發(fā)癌組相比,可疑的LS相關(guān)子宮內(nèi)膜癌組中,無(wú)肥胖(BMI28 kg/m2)(p=0.04)、高級(jí)別腫瘤(p=0.012)、曾經(jīng)或同時(shí)發(fā)生其他部位腫瘤(p=0.009)更常見(jiàn);年齡,高血壓、糖尿病病史,家族腫瘤史,組織學(xué)類型,腫瘤部位,FIGO分期,肌層浸潤(rùn),淋巴結(jié)轉(zhuǎn)移,淋巴管、血管浸潤(rùn)等臨床病理特征無(wú)顯著性差異(p0.05)。3.各MMR蛋白缺失組中,MSH6和PMS2蛋白缺失組中,高級(jí)別腫瘤更常見(jiàn)(p=0.000)。4.與散發(fā)癌相比,MSH2/MSH6缺失組中BMI28 Kg/m2和具有家族腫瘤病史患者更常見(jiàn);MSH6和PMS2缺失組中,高級(jí)別腫瘤更多見(jiàn)(p0.05)。5.檢測(cè)48例MLH1蛋白缺失子宮內(nèi)膜癌的癌組織中MLH1基因啟動(dòng)子甲基化狀態(tài),因?yàn)闃?biāo)本組織提取DNA量不足或質(zhì)量不達(dá)標(biāo),獲得滿意結(jié)果14例,14例癌組織均存在MLH1基因啟動(dòng)子甲基化。結(jié)論:1.山西地區(qū)可疑LS相關(guān)子宮內(nèi)膜癌約占全部子宮內(nèi)膜癌病例的26%。2.有異時(shí)腫瘤病史或同時(shí)發(fā)生其它部位腫瘤的EC患者,應(yīng)高度警惕LS的發(fā)生。3.與散發(fā)性相比,LS相關(guān)子宮內(nèi)膜癌無(wú)肥胖、高級(jí)別的患者更常見(jiàn)。4.MLH1基因啟動(dòng)子甲基化是MLH1基因常見(jiàn)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.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R737.33

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 馬辛欣;王建六;;子宮內(nèi)膜癌診斷方法[J];國(guó)際婦產(chǎn)科學(xué)雜志;2014年04期

2 黃驍昊;韓素萍;;Lynch綜合征相關(guān)子宮內(nèi)膜癌的診治進(jìn)展[J];醫(yī)學(xué)綜述;2014年12期

3 王軼英;王悅;寧燕;孔北華;鄭文新;;Lynch綜合征相關(guān)婦科腫瘤的臨床思考[J];現(xiàn)代婦產(chǎn)科進(jìn)展;2013年07期

4 楊繼清;劉新良;邵永孚;;Lynch綜合征診治進(jìn)展[J];河北醫(yī)藥;2013年14期

5 方園;王魯平;;結(jié)直腸癌微衛(wèi)星不穩(wěn)定性檢測(cè)的臨床病理意義及方法[J];診斷病理學(xué)雜志;2012年03期

6 丁元升;張劍權(quán);;遺傳性非息肉病性大腸癌的臨床研究進(jìn)展[J];中國(guó)現(xiàn)代醫(yī)藥雜志;2010年10期

7 徐俊榮;宋瑛;;林奇綜合征的診治進(jìn)展[J];胃腸病學(xué)和肝病學(xué)雜志;2010年10期

8 陳明清;;遺傳性非息肉性大腸癌研究進(jìn)展[J];昆明醫(yī)學(xué)院學(xué)報(bào);2010年02期

9 呂健;;G家族百年與Lynch綜合征研究進(jìn)展[J];醫(yī)學(xué)綜述;2007年01期

10 ;Clinical phenotype and prevalence of hereditary nonpolyposis colorectal cancer syndrome in Chinese population[J];World Journal of Gastroenterology;2005年10期

，

本文編號(hào)：1745966