非小细胞肺癌的PD-L1表达与临床病理学特征的相关性研究  

Expression of PD-L1 in non-small cell lung cancer and its association with clinicopathological features

作　　者：屈晓蝶 董宇杰[1] 周立娟[1] 赵丹[1] 张晨[1] 苏丹[1] 车南颖[1] QU Xiao-die;DONG Yu-jie;ZHOU Li-juan;ZHAO Dan;ZHANG Chen;SU Dan;CHE Nan-ying(Department of Pathology,Beijing Key Laboratory for Drug Resistant Tuberculosis,Beijing Chest Hospital,Capital Medical University,Beijing Tuberculosis and Thoracic Tumor Research Institute,Beijing 101149,China)

机构地区：[1]首都医科大学附属北京胸科医院北京市结核病胸部肿瘤研究所病理科耐药结核病研究北京市重点实验室,北京101149

出　　处：《诊断病理学杂志》2021年第10期821-825,830,共6页Chinese Journal of Diagnostic Pathology

基　　金：北京市科技计划医药协同科技创新研究(Z181100001918027);北京市科委首都临床诊疗技术研究及示范应用项目(Z191100006619079);北京市医管局登峰计划(DFL20181601);北京市医院管理中心“青苗”计划专项经费资助(QML20191601);通州区高层次人才发展支持计划(YHLD2018006,YHLD2019036)。

摘　　要：目的探讨程序性死亡配体1(PD-L1)在非小细胞肺癌(NSCLC)中的表达及其与NSCLC临床病理特征的相关性。方法收集2019-05—2020-05间首都医科大学附属北京胸科医院住院的1227例NSCLC患者的临床病理资料,采用免疫组织化学法检测PD-L1蛋白,应用ARMS法和二代测序技术检测NSCLC相关驱动基因,分析PD-L1与NSCLC临床病理特征的相关性。结果1227例患者中PD-L1阳性572例(46.6%),logistic回归模型结果显示有吸烟史(OR=1.456,P=0.036)、鳞癌(OR=1.798,P<0.001)、临床分期晚(III-IV期)(OR=1.384,P=0.034)以及有淋巴结转移(OR=1.547,P=0.003)是PD-L1表达阳性的独立危险因素。PD-L1表达在角化型鳞癌与非角化型鳞癌之间没有显著差异(P=0.763),而在腺癌中,实体型和微乳头型表达高于其他组织学类型(P<0.001)。并且,PD-L1表达阳性与KRAS突变及ALK阳性呈正相关(P=0.018,P=0.009),而与EGFR突变呈负相关性(P<0.001)。此外,PD-L1表达在不同标本类型之间具有差异性,Kappa一致率为0.315。结论PD-L1在NSCLC中的表达与KRAS突变和ALK阳性具有相关性,提示KRAS突变和ALK阳性患者可能在PD-L1抑制剂免疫治疗中获益更多。Objective To analyze programmed cell death ligand 1(PD-L1)expression in non-small cell lung cancer(NSCLC)and its association with clinicopathological features.Methods We retrospectively analyzed clinicopathological data of 1,227 NSCLC patients hospitalized in Beijing Chest Hospital of Capital Medical University from May 2019 to May 2020.PD-L1 expression was detected with immunohistochemical staining.The gene mutation status of NSCLC were examined with ARMS and NGS method.Results Among the 1227 patients,PD-L1 was positive in 572(46.6%)patients.The logistic regression model showed smoking(OR=1.456,P=0.036),squamous cell carcinoma(OR=1.798,P<0.001),advanced stage(Stage III-IV)(OR=1.384,P=0.034)and lymph node metastasis(OR=1.547,P=0.003)were independent risk factors for positive expression of PD-L1.The expression of PD-L1 was not significantly different between keratinizing squamous cell carcinoma and non-keratinizing squamous cell carcinoma(P=0.763),and in lung adenocarcinoma,the expression of PD-L1 in solid pattern and micropapillary subtype were higher than other subtypes(P<0.001).In addition,PD-L1 had positive association with KRAS mutations and ALK gene fusion(P=0.018,P=0.009),while it had a converse relationship with EGFR mutation(P<0.001).Moreover,the present study found that PD-L1 expression between biopsy and surgical specimen was different,and the Kappa agreement rate was 0.315.Conclusion PD-L1 expression in NSCLC is significantly associated with KRAS mutation and ALK rearrangement,suggesting that patients with KRAS mutation and ALK rearrangement may be benefit more from mmunotherapy with PD-L1 inhibitors.

关 键 词：非小细胞肺癌 程序性死亡配体1 临床病理特征 

分 类 号：R730.267[医药卫生—肿瘤]