微卫星不稳定对子宫内膜样癌组织PD-L1和CD8表达影响及意义  

Effect of microsatellite instability on the expression of PD-L1 and CD8 in endometrioid carcinoma and their significance

作　　者：石洪堂 刘志强[1] 孟玮[2] 李红[3] 郭庆枝[1] 许振[1] SHI Hongtang;LIU Zhi-qiang;MENG Wei;LI Hong;GUO Qing-zhi;XU Zhen(Affiliated Hospital of Binzhou Medical College,Binzhou 256600,P.R.China)

机构地区：[1]滨州医学院附属医院妇科,山东滨州256600 [2]滨州医学院附属医院中心实验室,山东滨州256600 [3]滨州医学院附属医院病理科,山东滨州256600

出　　处：《中华肿瘤防治杂志》2020年第12期958-962,985,共6页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的子宫内膜癌的发病呈现持续上升和年轻化趋势,微卫星不稳定在内膜癌形成及免疫治疗方面的作用逐渐被认识。本研究探讨微卫星不稳定性对子宫内膜样癌中PD-L1和CD8表达的影响,分析其作为免疫治疗标志物的价值及PD-L1表达定位。方法选取2016-01-01-2018-09-30滨州医学院附属医院收治的116例手术治疗且术后检测过MMR蛋白(MLH1、MSH2、MSH6、PMS2)的内膜样癌病例为研究对象,根据MMR蛋白表达结果分为MSI组(37例)与MSS组(79例),分析两组病例的临床病理特征,免疫组化检测两组石蜡切片PD-L1和CD8表达,分析其表达与MSI关系以及PD-L1表达定位。结果 MSI组与MSS组的临床病理特征差异无统计学意义,均P<0.05。MSI组微环境中PD-L1的阳性表达率为51.4%,高于MSS组的26.6%,χ^2=6.843,P=0.009;进一步分析发现,MSI组PD-L1在免疫细胞阳性率为43.2%,高于MSS组的16.5%,χ^2=9.644,P=0.002。MSI组病例中CD8的阳性率为56.8%,高于MSS组的25.3%,差异均有统计学意义,χ^2=10.900,P=0.001。PD-L1在MSI组肿瘤细胞的阳性率为21.6%,MSS组为19.0%,差异无统计学意义,χ^2=0.110,P>0.05。结论 MSI可能上调子宫内膜样癌免疫微环境中PD-L1与CD8的表达,并且主要上调PD-L1在免疫细胞的表达,可以作为Ⅰ型内膜癌患者用PD-1/PD-L1途径免疫治疗的标志物。OBJECTIVE The incidence of endometrial cancer continues to rise and rejuvenate.The role of microsatellite instability in the formation of endometrial cancer and immunotherapy is gradually recognized.This study detected the microsatellite instability on endometrial cancer and the influence of PD-L1 and CD8 expression on the value of immunotherapy markers and the expression of PD-L1 expression.METHODS A total of 116 cases of endometrial cancer treated with MMR protein(MLH1,MSH2,MSH6,PMS2)were selected from the Affiliated Hospital of Binzhou Medical College from January 01,2016 to September 30,2018.The subjects were divided into MSI group(37 cases)and MSS group(79 cases)according to the MMR protein expression results.The clinical characteristics of the two groups were analyzed.The expressions of PD-L1 and CD8 in the paraffin sections of the two groups were analyzed by immunohistochemistry.The relationships between expression and MSI and PD-L1 were analyzed.RESULTS There were no significant differences in the clinical case characteristics of 116 patients.The positive expression rate of PD-L1 in the microenvironment of MSI group was 51.4%,which was significantly higher than that(26.6%)in MSS group(χ^2=6.843,P=0.009).Further analysis showed that the positive rate of PD-L1 in immune cells was significantly higher than that(16.5%)in MSS group(χ^2=9.644,P=0.002),and the positive expression rate of PD-L1 in MSI group was 21.6%,compared with 19.0%in MSS group.With statistical significance(χ^2=0.110,P>0.05),the positive rate of CD8 in the MSI group was 56.8%,which was significantly higher than that(25.3%)in the MSS group(χ~2=10.900,P=0.001).CONCLUSIONS MSI may up-regulate the expression of PD-L1 and CD8 in the immune microenvironment of endometrioidcarcinoma,and MSI mainly up-regulates the expression of PD-L1 in immune cells.MSI can be used as PD-1/PD-L1 pathway for immunotherapy markers in patients with typeⅠendometrial cancer.

关 键 词：子宫内膜样癌 微卫星不稳定 免疫微环境 免疫治疗 PD-L1 

分 类 号：R737.33[医药卫生—肿瘤]