错配修复基因蛋白在子宫内膜样腺癌中的表达及其预后意义  

Expression of mismatch repair gene in endometrioid adenocarcinoma and its prognostic significance

作　　者：古丽米拉·巴依坦 张巍[2] 余丽 

机构地区：[1]新疆维吾尔自治区人口和计划生育科研所病理科,乌鲁木齐830011 [2]新疆医科大学第一附属医院病理科 [3]新疆维吾尔自治区昌吉市第二人民医院病理科

出　　处：《肿瘤研究与临床》2014年第9期608-612,616,共6页Cancer Research and Clinic

基　　金：新疆维吾尔自治区科技计划项目（201233142）

摘　　要：目的 探讨子宫内膜样腺癌中DNA错配修复基因（MMR） MLH1、MSH2、PMS2和MSH6的表达,并分析其临床病理意义.方法 应用免疫组织化学法检测DNA错配修复蛋白MLH1、MSH2、PMS2和MSH6在101例子宫内膜样腺癌组织中的表达,确定肿瘤的微卫星不稳定性（MSI）和微卫星稳定（MSS）表型,并分析其与发病年龄、肿瘤分化、肌层浸润程度、淋巴结转移及预后的关系.结果 101例子宫内膜样腺癌组织中全子宫切除术67例,内膜活组织检查34例.随访资料完整者66例,其中手术标本52例,活组织检查标本14例.MLH1、MSH2、PMS2和MSH6失表达率分别为31.6％（32/101）、28.7％（29/101）、16.8％（17/101）、8.9％（9/101）;MSI表型53.5％（54/101）,MSS表型46.5％（47/101）.单因素分析：在子宫切除术组织中低频MSI（MSI-L）合并MSS组（34例）预后优于高频MSI（MSI-H）组（18例;P=0.041）.肿瘤肌层浸润深度、分化程度、年龄与子宫内膜样腺癌预后之间差异具有统计学意义（P＜0.05）.COX多因素分析：肿瘤肌层浸润深度和年龄与宫内膜样腺癌预后间差异具有统计学意义（P=0.034,P=0.009）,而MSI-L合并MSS组与MSI-H组相比较,两组预后差异无统计学意义（P＞0.05）.结论 MSI是子宫内膜样腺癌发生的分子事件之一,年龄和肿瘤浸润深度是子宫内膜样腺癌独立的预后因素.鉴于MSI与预后关系在本研究中单因素和多因素分析结果的不一致性,MSI是否可以作为子宫内膜样腺癌预后评价的确定依据,需要进一步验证.Objective To explore the expression of mismatch repair gene （MMR） （MLH1,MSH2,PMS2 and MSH6） in endometrioid adenocarcinoma,and to analyze its clinical pathological significance.Methods Inmunohistochemical EnVision method was used to detect the expressions of DNA mismatch repair proteins （MLH1,MSH2,PMS2 and MSH6） in 101 cases of endometrial adenocarcinoma.The phenotypes of tumor microsatellite instability （MSI） and microsatellite stable were determined,and its relationship with onset age,differentiation,depth of myometrial invasion,lymphatic metastasis and prognosis of tumor were analyzed.Results There were 67 cases of hysterectomy and 34 cases of endometrial biopsy in 101 cases of endometrial adenocarcinoma.52 cases of surgical specimens and 14 cases of biopsy specimens were included in 66 cases that had complete follow-up data.Rates of negative expression were as follows：MLH1 31.6 ％ （32/101）,MSH228.7 ％ （29/101）,PMS2 16.8 ％ （17/101）,MSH6 8.9 ％ （9/101）.MSI phenotype 53.5 ％ （54/101）,MSS phenotype 46.5 ％ （47/101）.Univariate analysis showed that prognoses of MSI-L＆MSS group （34 cases） were better than those of MSI-H group （18 cases） in hysterectomy organization （P =0.041）.The differences between depth of myometrial invasion,degree of differentiation,age and prognosis of endometrial adenocarcinoma were statistically significant （P ＜0.05）.Cox multivariate analysis showed that differences between depth of myometrial invasion,age and prognosis of endometrial adenocarcinoma were statistically significant （P =0.034,P =0.009）,while there was no significant difference between MSI-L＆MSS group and MSI-H group in prognosis （P ＞ 0.05）.Conclusions MSI is one of the molecular events that occur in the endometrioid adenocarcinoma.Age and depth of tumor invasion are independent prognostic factors of endometrioid adenocarcinoma.In view of inconsistency between univariate analysis and multivariate analysis,whether MSI can be used as deterministic acco

关 键 词：错配修复基因 免疫组织化学 微卫星不稳定性 子宫内膜样腺癌 预后 

分 类 号：R737.33[医药卫生—肿瘤]