摘要目的 研究50岁以下中青年子宫内膜癌中DNA错配修复(MMR)基因 MLH1 、MSH2、MSH6和PMS2的表达情况,并分析这4项指标的表达与子宫内膜癌患者的体质量指数(BMI)、肿瘤分级及分期等临床病理特征的关系.方法 50岁以下子宫内膜癌女性作为实验组,50岁以下子宫内膜复杂不典型增生、子宫内膜单纯性增生、正常周期子宫内膜及60岁以上子宫内膜癌病例作为对照组,采用免疫组织化学SP法检测MMR蛋白,分别进行比较,观察上述各项指标在50岁以下女性子宫内膜良恶性病变中的表达规律.结果 40例子宫内膜腺癌患者中有27例(67.5％)至少有一种MMR蛋白表达阴性,在复杂不典型增生、单纯性增生和正常周期子宫内膜组中4项指标至少有一项为阴性的比例分别为5/15、1/13、1/11,实验组与对照组进行比较,差异具有统计学意义(P＜0.01).MLH1、MSH2、MSH6和PMS2蛋白在子宫内膜癌中的阴性表达率分别为52.5％、12.5％ 、35.0％和30.0％；与对照组分别进行比较,MLH1和MSH6的表达差异均有统计学意义(P＜0.05),MSH2的表达各组间差异均无统计学意义(P =0.295).MMR中4项指标的表达与子宫内膜癌的肿瘤分期和组织学分级无关,但MSH6的阴性表达更倾向于发生在高BMI病例中.结论 MMR基因突变与子宫内膜复杂不典型增生及子宫内膜癌的发生有一定的相关性,但在临床病理指标上,除MSH6缺失表达与高BMI相关外,其他4项MMR指标与子宫内膜癌的肿瘤分期和组织学分级无明显相关性.

abstractsObjective To investigate the expression of DNA mismatch repair (MMR) genes (MLH1,MSH2,MSH6 and PMS2) in endometrial adenocarcinoma (EC) of patients under 50 years and to explore the relationship between MMR expression and clinicopathological features including body mass index (BMI),histological grade and pathological stage of EC.Methods MMR gene expression was investigated by immunohistochemical S-P method in endometrial adenocarcinomas of patients under age of 50.The control groups included complexity atypical hyperplasia endometrium (CAHE),simple hyperplasia endometrium (SHE),normal endometrium (NE) of patients under age of 50 and EC of patients older than 65 years.Results Twenty seven of 40 EC (67.5％) lost at least one MMR protein expression.Loss of at least one MMR protein expression was seen in 5/15 cases of CAHE,1/13 SHE and 1/11 NE,respectively (P＜0.01).The rates of loss of expression of MLH1,MSH2,MSH and PMS2 proteins in EC were 52.5％,12.5％,35.0％,and 30.0％,respectively.The difference between MLH1 and MSH6 expression among the four groups were significant (P＜0.05),but the expression of MSH2 showed no significant difference among the groups (P =0.295).The expression of MMR protein had no relationship with histological grade and pathological stage,although loss of MSH6 was more frequently seen in patients of higher BMI.Conclusions Abnormal expression of MMR proteins is correlated with the development of EC from complex atypical hyperplasia.With the exception of the correlation of MSH6 expression with higher BMI,the expression of MMR proteins in EC has no significant relationship with histological grade and pathological stage.