子宫内膜癌微卫星不稳定发生情况及其与患者临床病理特征的关系

Microsatellite instability and its relationship with clinicopathological characteristics of patients with endometrial carcinoma

目的探讨子宫内膜癌患者微卫星不稳定(MSI)状态及其与患者临床病理特征的关系。方法回顾性分析2020年1月至2021年12月在山西省肿瘤医院行手术治疗的365例子宫内膜癌患者临床资料。采用免疫组织化学法检测365例患者术后肿瘤组织样本中4种DNA错配修复(MMR)蛋白(MLH1、MSH2、MHS6、PMS2)及雌激素受体(ER)、孕激素受体(PR)、p53突变型蛋白的表达情况。1种及以上MMR蛋白未表达为MSI组, 4种蛋白均表达为微卫星稳定(MSS)组。比较两组患者临床病理特征。采用φ系数分析MSI与ER、PR、p53突变型蛋白表达的关系。结果 365例患者年龄为(53±19)岁(21~83岁), 其中MSI组72例(19.7%), MSS组293例(80.3%)。不同年龄[>50岁比≤50岁:22.1%(61/276)比12.4%(11/89)]、肿瘤长径[≤2 cm比>2 cm:25.9%(30/116)比16.8%(42/249)]、国际妇产科联盟(FIGO)分期[Ⅲ~Ⅳ期比Ⅰ~Ⅱ期:31.1%(14/45)比18.1%(58/320)]、组织学类型[Ⅰ型比Ⅱ型:21.7%(71/327)比2.6%(1/38)]患者中MSI患者比例差异均有统计学意义(均P<0.05);不同浸润深度、分化程度、淋巴结转移情况、脉管受侵情况、病变部位的MSI患者比例差异均无统计学意义(均P>0.05)。Ⅰ型子宫内膜癌327例中, 黏液性腺癌1例(其微卫星状态为MSS), 其余326例均为内膜样腺癌;72例MSI患者中, 71例为内膜样癌, 另1例为Ⅱ型子宫内膜癌中3例混合性癌中的1例。MSI与突变型p53呈负相关关系(φ=-0.11, P=0.031), MSI与ER、PR关系的φ系数分别为-0.03、-0.06, 但差异均无统计学意义(P值分别为0.578、0.255)。结论 MSI子宫内膜癌多为内膜样腺癌, 子宫内膜癌MSI与患者年龄、FIGO分期、肿瘤长径、组织学类型相关, 且与突变型p53呈负相关。

Objective To explore the status of microsatellite instability(MSI)and its relationship with clinicopathological characteristics of patients with endometrial carcinoma.Methods The clinical data of 365 patients with endometrial carcinoma who received surgery in Shanxi Province Cancer Hospital between January 2020 and December 2021 were retrospectively analyzed.Immunohistochemistry was used to detect the expressions of 4 DNA mismatch repair(MMR)proteins(MLH1,MSH2,MHS6,and PMS2),estrogen receptor(ER),progesterone receptor(PR),and p53 mutant protein in postoperative cancer tissue samples from 365 patients with endometrial carcinoma.All patients were divided into MSI group(1 or more non-expression of MMR protein)and microsatellite stability(MSS)group(4 proteins were all expressed),and the clinicopathological characteristics of patients in both groups were compared.φefficient was used to analyze the correlation of MSI with ER,PR,p53 mutant protein expressions.Results There were 72 cases(19.7%)in MSI group and 293 cases(80.3%)in MSS group;and the age of all patients was(53±19)years(21-83 years).There were statistically significant differences in the proportion of MSI patients in endometrial carcinoma patients with different age[>50 years vs.≤50 years:22.1%(61/276)vs.12.4%(11/89)],tumor diameter[≤2 cm vs.>2 cm:25.9%(30/116)vs.16.8%(42/249)],International Federation of Gynecology and Obstetrics(FIGO)staging[stageⅢ-Ⅳvs.stageⅠ-Ⅱ:31.1%(14/45)vs.18.1%(58/320)],histological type[typeⅠvs.typeⅡ:21.7%(71/327)vs.2.6%(1/38)](all P<0.05).There were no statistically significant differences in the proportion of MSI patients with different depth of invasion,degree of differentiation,lymph node metastasis,vascular involvement,and lesion location(all P>0.05).Among 327 cases of typeⅠendometrial carcinoma,1 case was mucinous adenocarcinoma(MSS status),and the other 326 cases were endometrioid adenocarcinoma.Of the 72 patients with MSI,71 cases were endometrioid carcinoma and the other was 1 of 3 mixed carcinomas in typeⅡendometrial carcinoma.There was a negative correlation between MSI and mutant p53(φcoefficient was-0.11,P=0.031),andφcoefficient of the correlation of MSI with ER and PR was-0.03 and-0.06,while there were no statistically significant differences(P value was 0.578 and 0.255,respectively).Conclusions Endometrioid adenocarcinoma is the main type of endometrial cancer patients with MSI.MSI in endometrial cancer is correlated with age,FIGO staging,tumor diameter and histological type of patients,while negatively correlated with mutant p53.