免疫检查点B7同源物4在子宫内膜癌组织中的表达及其临床意义  

Expression and significance of immune checkpoint B7-homolog 4 in endometrial cancer

作　　者：宗丽菊 向阳[1] 于双妮[2] 卢朝辉[2] 陈杰[2] 黄卫红 Zong Liju;Xiang Yang;Yu Shuangni;Lu Zhaohui;Chen Jie;Huang Weihong(Department of Obstetrics and Gynecology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Pathology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730,China;Department of Obstetrics and Gynecology,Zhongshan Hospital,Fudan University,Shanghai 200032,China)

机构地区：[1]中国医学科学院北京协和医院妇产科,北京100730 [2]中国医学科学院北京协和医院病理科,北京100730 [3]复旦大学附属中山医院妇产科,上海200032

出　　处：《中华妇产科杂志》2022年第12期921-931,共11页Chinese Journal of Obstetrics and Gynecology

基　　金：国家自然科学基金(82001664);北京市自然科学基金(7222126);首都卫生发展科研专项(2022-1-4011);中国医学科学院中央级公益性科研院所基本科研业务费专项资金(2021-PT320-001);北京康华中西医发展基金会妇科肿瘤专项研究(KH-2021-LLZX-007)。

摘　　要：目的探讨免疫检查点B7同源物4(B7-H4)在子宫内膜癌组织中的表达及其临床意义。方法选择2009年至2019年中国医学科学院北京协和医院收治的833例子宫内膜癌患者。采用免疫组化EnVision二步法检测子宫内膜癌组织中B7-H4、错配修复(MMR)、p53、细胞程序性死亡配体1(PD-L1)蛋白的表达及CD_(8)^(+)T淋巴细胞密度;采用第一代测序技术(Sanger法)对子宫内膜癌组织进行分子分型检测。比较不同临床病理特征、分子分型、PD-L1蛋白表达、CD_(8)^(+)T淋巴细胞密度的子宫内膜癌组织中B7-H4蛋白阳性表达率的差异;对其中随访时间≥3个月的664例患者进行预后[包括无复发生存率(RFS)和疾病特异性生存率(DSS)]分析,其中位随访时间为31个月(范围:4~121个月),采用Cox比例风险回归模型对影响子宫内膜癌患者预后的相关因素进行单因素和多因素分析。结果(1)833例子宫内膜癌患者的中位年龄为58岁(范围:25~88岁);病理类型:子宫内膜样癌595例,非子宫内膜样癌238例;手术病理分期:Ⅰ期542例,Ⅱ期38例,Ⅲ期173例,Ⅳ期45例,不详35例。590例患者完成了分子分型检测,其中POLE突变型50例,错配修复缺陷(MMR-d)型163例,无特异性分子改变(NSMP)型246例,p53突变型131例。(2)在子宫内膜癌的细胞膜和细胞质中B7-H4蛋白呈棕黄色阳性表达,子宫内膜癌组织中B7-H4蛋白的阳性表达率为71.5%(596/833)。不同年龄、手术病理分期、肿瘤级别、病理类型、肌层浸润深度、有无淋巴脉管间隙浸润、分子分型患者的B7-H4蛋白阳性表达率分别比较,差异均有统计学意义(P均<0.05);而不同PD-L1蛋白表达及CD_(8)^(+)T淋巴细胞密度患者的B7-H4蛋白阳性表达率分别比较,差异则均无统计学意义(P均>0.05)。B7-H4蛋白阳性患者的5年RFS和DSS(83.9%、87.3%)分别与B7-H4蛋白阴性患者(77.2%、78.1%)比较均有增高趋势,但分别比较,差异均无统计学意义(P=0.053,P=0.083)。(3)�Objective To investigate the expression of B7 homolog 4(B7-H4)and its clinical significance in endometrial cancer.Methods A total of 833 patients with endometrial cancer admitted to Peking Union Medical College Hospital,Chinese Academy of Medical Sciences from 2009 to 2019,were enrolled.The expression of B7-H4,mismatch repair(MMR),p53,programmed cell death ligand 1(PD-L1)protein,and CD_(8)^(+)T lymphocyte density in endometrial cancer tissues were detected by the EnVision two-step method of immunohistochemical staining.First-generation sequencing(Sanger method)was used to determine molecular subtyping of endometrial cancer.Theχ2 test was used to compare the differences in positive expression rate of B7-H4 protein in endometrial cancer tissues with different clinicopathological features and molecular subtyping,PD-L1 protein expression,and CD_(8)^(+)T lymphocyte density.Survival analyses[including recurrence-free survival(RFS)and disease-specific survival(DSS)]were performed for 664 patients with follow-up time≥3 months,with a median follow-up time of 31 months(range:4-121 months),and the Cox proportional hazards regression model was used to analyze the relevant factors affecting the prognosis of patients with endometrial cancer.Results(1)The median age of 833 patients was 58 years(range:25-88 years);pathological type:595 with endometrioid carcinoma,238 with non-endometrioid carcinoma;surgical-pathological staging:542 cases at stageⅠ,38 cases at stageⅡ,173 cases at stageⅢ,and 45 cases at stageⅣ.Molecular subtyping was performed in 590 patients,including 50 with POLE mutation,163 with mismatch repair defect(MMR-d)type,246 with nospecific molecular change(NSMP)type,and 131 with p53 mutation subtype.(2)B7-H4 protein was expressed with brownish-yellow stainind in the cell membrane and cytoplasm of endometrial carcinoma,and the positivity rate of B7-H4 protein was 71.5%(596/833).The positivity rates of B7-H4 protein among patients with different age,surgical-pathological stage,tumor grade,pathological type,de

关 键 词：子宫内膜肿瘤 B7同源物4 预后 生物标记 肿瘤 

分 类 号：R737.33[医药卫生—肿瘤]