肺小细胞癌免疫治疗相关的分子标志物检测  

Detection of immunotherapy-associated molecular biomarkers in small cell lung cancer

作　　者：陈龙云[1] 刘笑玎 庞钧译 胡梅珍 黄璐嘉 吴艳艳 师晓华[1] 梁智勇[1] CHEN Long-yun;LIU Xiao-ding;PANG Jun-yi;HU Mei-zhen;HUANG Lu-jia;WU Yan-yan;SHI Xiao-hua;LIANG Zhi-yong(Department of Pathology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China;OrigiMed Shanghai Co,Ltd)

机构地区：[1]中国医学科学院北京协和医学院北京协和医院病理科,北京100730 [2]至本医疗科技(上海)有限公司

出　　处：《诊断病理学杂志》2022年第2期132-136,共5页Chinese Journal of Diagnostic Pathology

基　　金：国家自然科学基金青年基金(81802957)。

摘　　要：目的 探讨肺小细胞癌(SCLC)中免疫治疗分子标志物程序性死亡配体1(PD-L1)及肿瘤突变负荷(TMB)与临床病理特征的相关性及预后分析。方法 回顾性收集北京协和医院2008—2018年间SCLC病例组织标本50例,并收集相应临床病理资料;采用免疫组织化学(IHC)染色检测PD-L1在肿瘤细胞和肿瘤浸润淋巴细胞(TILs)的表达,通过包含638基因的靶向测序检测TMB,分析TMB与PD-L1表达的相关性。通过生存分析探究PD-L1表达和TMB的预后意义。结果 本研究中共纳入50例SCLC病例,16例为活检标本,34例为手术标本。5例病例PD-L1表达在肿瘤细胞中呈阳性,45例在TILs中阳性。通过临床病理分析发现,PD-L1肿瘤细胞阳性表达与年龄呈正相关(P=0.020);生存分析发现,TILs的PD-L1表达评分≥85%时,患者无进展生存期(PFS)更短(P=0.042)。当以5.2突变/Mb为界值将TMB分组分析时,TMB与PD-L1在肿瘤细胞中的表达相关(P=0.048)。结论 肿瘤细胞PD-L1阳性表达患者多为年轻的SCLC,PD-L1在TILs中的表达与SCLC患者PFS呈正相关;TMB以5.2突变/Mb为界值时与PD-L1在肿瘤细胞中表达相关。SCLC相关分子标志物检测对免疫治疗具有指导作用,并对预后具有预测意义。Objective To explore the association between immunotherapy-related molecular markers in small cell lung cancer(SCLC),programmed death-ligand 1(PD-L1),tumor mutation burden(TMB) and clinicopathological characteristics and their prognostic value.Methods The tissue samples of SCLC cases from 2008 to 2018 were retrospectively retrieved from the Peking Union Medical College Hospital,and the corresponding clinicopathological data were collected.Immunohistochemical(IHC) staining was used to detect the expression of PD-L1 in tumor cells.TMB was detected and analyzed by targeted sequencing containing 638 gene panel.Results A total of 50 SCLC cases were included in this study,16 were biopsy specimens,34 were surgical specimens.Totally,5 cases had PD-L1 positive in tumor cells;45 cases were TILs positive.And through clinicopathological analysis,positive expression of PD-L1 tumor cells was positively correlated with age(P=0.002).Survival analysis showed that patients had shorter progressive survival(PFS) when the expression score of PD-L1 in TILs was higher than 85(P=0.042).TMB was associated with PD-L1 expression in tumor cells when the cut-off values was defined as 5.2 mutation/Mb.Conclusion The age of SCLC patients is positively correlated with the expression of PD-L1 in tumor cells;the expression of PD-L1 in TILs is positively correlated with PFS.The detection of immunotherapy-related biomarkers could guide clinical practice and has prognostic value.

关 键 词：肺小细胞癌 程序性死亡配体1 肿瘤浸润淋巴细胞 肿瘤突变负荷 

分 类 号：R730.267[医药卫生—肿瘤]