摘要目的 探究晚期肺腺癌患者程序性死亡分子配体1(PD-L1)的表达情况以及4种不同克隆号PD-L1抗体免疫组织化学检测平台的一致性,以期为有效筛选晚期肺腺癌患者程序性死亡分子1(PD-1)/PD-L1抑制剂免疫治疗潜在获益人群提供临床试验依据.方法 采用多中心回顾性研究,收集4个中心于2017年8至12月诊断为晚期肺腺癌的活检标本共57例,患者平均年龄59岁(34～81岁);男性29例,女性28例.对蜡块进行连续切片并同时进行4种不同克隆号PD-L1抗体免疫组织化学染色.分别为22C3(Dako公司)、28-8(Abcam公司)、SP263(Ventana公司)和SP142(Ventana公司),其中22C3配套Dako公司二抗体系及全自动染色仪,其余二抗体系为Ventana Ultraview检测体系及自动染色仪.免疫组织化学染色切片由2位经过培训的高年资病理医师进行双盲独立阅片,对PD-L1阳性的肿瘤细胞按百分比进行判读.判读结果按<1％、1％～24％、25％～49％及≥50％4个级别进行统计比对.结果 以Dako公司22C3和二抗体系检测作为标准,PD-L1≥50％的病例共计8例,占14.0％(8/57);22C3、28-8及SP263对肿瘤细胞染色一致性较高(ρ=0.729～0.809);2位医师对PD-L1阳性的肿瘤细胞判读一致性较高(ρ=0.707～0.896),22C3及SP263结果显示尤为明显.结论 22C3、28-8及SP263在肿瘤细胞染色上具有较高的一致性.该研究在一定程度可为筛选免疫治疗潜在获益人群提供有效的临床试验.

abstractsObjective To analyze the expression of programmed death ligand 1 ( PD-L1 ) in patients with advanced lung adenocarcinoma and the consistency of four PD-L1 immunohistochemical detection platforms, with an aim of establishing baseline information to predict and select patients for programmed death 1 ( PD-1 )/PD-L1 immune inhibitor therapy. Methods This was a multi-center retrospective study, collecting totally 57 advanced lung adenocarcinoma biopsy specimens from four centers from August 2017 to December 2017. The mean age of 57 patients was 59 ( range 34-81) years, and 29 cases were male, 28 cases were female. Four PD-L1 immunohistochemical stains were done for each case, including 22C3 (Dako), 28-8 (Abcam), SP263 (Ventana), and SP142 (Ventana). Among them, 22C3 staining was done using Dako autostainer, and for the other three antibodies, Ventana Ultraview detection system and autostainer was used. The immunohistochemical slides were read by two trained histopathologists in a double-blinded way, and the percentage of PD-L1 positive tumor cells was assessed as <1％, 1％-24％, 25％-49％ and more than 50％. Results The Dako 22C3 was used as the standard. There were eight cases in which the PD-L1 staining was more than 50％ ( 14. 0％,8/57) . The staining consistency of tumor cells was higher in 22C3, 28-8 and SP263 (ρ=0. 729-0. 809). The two scoring doctors had a high degree of concordance in PD-L1 positive tumor cells (ρ=0. 707-0. 896), and this was most noticeable in 22C3 and SP263. Conclusions 22C3, 28-8 and SP263 show high consistency in tumor cell staining. The study can provide an effective basis for screening for potential patient population that may benefit from immunotherapy.