PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project
PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project
复制标题
DOI：
10.1016/j.jtho.2016.11.2228
复制
发表时间：
2017-02-01
影响因子：
20.4
通讯作者：
Kerr, Keith M.
中科院分区：
文献类型：
--
作者：
Hirsch, Fred R.;McElhinny, Abigail;Kerr, Keith M.
简介：Blueprint程序性死亡配体1（PD-L1）免疫组织化学（IHC）检测比较项目是一个工业-学术合作伙伴关系，旨在提供临床试验中使用的四种PD-L1 IHC检测的分析和临床可比性信息。采用临床试验中使用的4种PD-L1 IHC检测试剂（22 C3、28-8、SP142和SP263）对共计39例NSCLC肿瘤进行染色。三位专家在解释各自的测定时独立地评价了任何强度下肿瘤和免疫细胞染色阳性的百分比。临床诊断性能进行了评估，通过比较患者的分类以上和以下选定的表达cutoffs. Results和协议使用各种组合的分析和cutoffs.Results：分析比较表明，PD-L1染色的肿瘤细胞的百分比是相当的，当使用22 C3，28-8，和SP263检测，而SP142检测表现出更少的染色肿瘤细胞的整体。四种试验中免疫细胞染色的变异性似乎高于肿瘤细胞染色。在38例病例中，19例（50.0%）分类高于所有测定的选定临界值，5例（13%）分类低于所有测定的选定临界值。对于38例中的14例（37%），将根据使用的检测/评分系统进行不同的PD-L1分类。结论：Blueprint PD-L1 IHC检测比较项目显示，四种检测中有三种在肿瘤细胞染色上紧密对齐，而第四种检测显示染色的肿瘤细胞始终较少。所有试验均显示免疫细胞染色，但变异性大于肿瘤细胞染色。通过比较检测试剂盒和临界值，该研究表明，尽管三种检测试剂盒的PD-L1表达分析性能相似，但互换检测试剂盒和临界值会导致某些患者PD-L1状态的“错误分类”。需要更多的数据来告知使用替代染色检测来读取不同的特定治疗相关PD-L1临界值。(C)2017年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
Introduction: The Blueprint Programmed Death Ligand 1 (PD-L1) Immunohistochemistry (IHC) Assay Comparison Project is an industrial-academic collaborative partnership to provide information on the analytical and clinical comparability of four PD-L1 IHC assays used in clinical trials.Methods: A total of 39 NSCLC tumors were stained with four PD-L1 IHC assays (22C3, 28-8, SP142, and SP263), as used in the clinical trials. Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity. Clinical diagnostic performance was assessed through comparisons of patient classification above and below a selected expression cutoff and by agreement using various combinations of assays and cutoffs.Results: Analytical comparison demonstrated that the percentage of PD-L1-stained tumor cells was comparable when the 22C3, 28-8, and SP263 assays were used, whereas the SP142 assay exhibited fewer stained tumor cells overall. The variability of immune cell staining across the four assays appears to be higher than for tumor cell staining. Of the 38 cases, 19 (50.0%) were classified above and five (13%) were classified below the selected cutoffs of all assays. For 14 of the 38 cases (37%), a different PD-L1 classification would be made depending on which assay/scoring system was used.Conclusions: The Blueprint PD-L1 IHC Assay Comparison Project revealed that three of the four assays were closely aligned on tumor cell staining whereas the fourth showed consistently fewer tumor cells stained. All of the assays demonstrated immune cell staining, but with greater variability than with tumor cell staining. By comparing assays and cutoffs, the study indicated that despite similar analytical performance of PD-L1 expression for three assays, interchanging assays and cutoffs would lead to "misclassification" of PD-L1 status for some patients. More data are required to inform on the use of alternative staining assays upon which to read different specific therapy-related PD-L1 cutoffs. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.