A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non-Small Cell Lung Cancer.
A Prospective, Multi-institutional, Pathologist-Based Assessment of 4 Immunohistochemistry Assays for PD-L1 Expression in Non-Small Cell Lung Cancer.
复制标题
DOI：
10.1001/jamaoncol.2017.0013
复制
发表时间：
2017-08-01
期刊：
影响因子：
28.4
通讯作者：
Wistuba II
中科院分区：
文献类型：
--
作者：
Rimm DL;Han G;Taube JM;Yi ES;Bridge JA;Flieder DB;Homer R;West WW;Wu H;Roden AC;Fujimoto J;Yu H;Anders R;Kowalewski A;Rivard C;Rehman J;Batenchuk C;Burns V;Hirsch FR;Wistuba II
FDA已注册了四种检测PD-L1的检测试剂盒，以丰富患者对抗PD-1/PD-L1治疗的反应。这些测试在两个单独的染色平台上使用四种单独的PD-L1抗体，并有自己的评分系统，这引发了关于其相似性和潜在交叉利用的问题。我们比较了四种PD-L1平台的性能，包括两种FDA批准的检测试剂盒和两种实验室开发的检测试剂盒（LDT）。将90个存档NSCLC的4个连续组织学切片分配至3个研究中心，进行以下IHC：1）Dako Link 48上的28-8抗体; 2）Dako Link 48上的22 c3抗体; 3）Ventana Benchmark上的SP142抗体; 4）Leica Bond上的E1 L3 N抗体。由13名病理学家通过估计表达PD-L1的恶性细胞和免疫细胞的百分比对载玻片进行扫描和评分。进行组内相关系数（ICC）以及配对和混合效应统计分析，以比较抗体和病理学家对肿瘤和免疫细胞的评分。SP142 Ventana检测是一个离群值，肿瘤和免疫细胞中PD-L1表达的平均评分均显著较低。成对比较显示28-8和E1 L3 N没有显著差异，但22 c3显示肿瘤细胞标记的轻微但统计学显著减少。使用13名病理学家肿瘤评分的平均值对抗体之间的ICC进行评价以量化测定间变异性，结果显示抗体之间肿瘤细胞评分的一致性非常高（0.813），而免疫细胞评分的一致性水平较低（0.277）。当检查任何单一抗体的病理学家间变异性时，病理学家对肿瘤的读数之间的一致性范围为每种抗体的ICC为0.83至0.88，而每种抗体的免疫细胞的ICC范围为0.17至0.23。使用SP142抗体的试验是一个明显的离群值，检测到显著更少的肿瘤细胞和免疫细胞PD-L1表达。抗体22 c3显示出比28-8或E1 L3 N轻微但统计学上显著更低的染色，但这种显著性仅在使用13个病理学家评分的平均值时检测到。病理学家在对用任何抗体染色的肿瘤细胞进行评分时显示出极好的一致性，但对免疫细胞染色进行评分的一致性较差。
Four assays have been registered with the FDA to detect PD-L1 to enrich for patient response to anti-PD-1/PD-L1 therapies. The tests use four separate PD-L1 antibodies on two separate staining platforms and have their own scoring systems which raises questions about their similarity and potential cross-utilization. We compared the performance of four PD-L1 platforms, including two FDA-cleared assays and two laboratory developed tests (LDTs). Four serial histology sections from 90 archival NSCLCs were distributed to three sites that performed the following IHCs: 1) 28-8 antibody on Dako Link 48; 2) 22c3 antibody on Dako Link 48; 3) SP142 antibody on Ventana Benchmark; and 4) E1L3N antibody on Leica Bond. Slides were scanned and scored by thirteen pathologists by estimating the percentage of malignant and immune cells expressing PD-L1. Intraclass correlation coefficients (ICC) and paired and mixed effects statistical analyses were performed to compare antibodies and pathologists scoring of tumor and immune cells. The SP142 Ventana assay was an outlier with a significantly lower mean score of PD-L1 expression in both tumor and immune cells. Pairwise comparisons showed the 28-8 and E1L3N were not significantly different, but that 22c3 showed a slight but statistically significant reduction in tumor cell labeling. Evaluation of ICC between antibodies to quantify inter-assay variability using the average of thirteen pathologists scores for tumor shows very high concordance between antibodies for tumor cell scoring (0.813) and lower levels of concordance for immune cell scoring (0.277). When examining inter-pathologists variability for any single antibody, the concordance between pathologists’ reads for tumor ranged from ICC of 0.83 to 0.88 for each antibody while the ICC from immune cells for each antibody ranged from 0.17 to 0.23. The assay using the SP142 antibody is a clear outlier detecting significantly less tumor cell and immune cell PD-L1 expression. Antibody 22c3 shows slight yet statistically significantly lower staining than either 28-8 or E1L3N, but this significance is only detected when using the average of thirteen pathologist scores. Pathologists show excellent concordance when scoring tumor cells stained with any antibody, but poor concordance for scoring immune cell staining.
登录
查看更多内容
影响因子：
20.4
作者：
Hirsch, Fred R.;McElhinny, Abigail;Kerr, Keith M.
通讯作者：
Kerr, Keith M.
影响因子：
17.1
作者：
Taube JM;Anders RA;Young GD;Xu H;Sharma R;McMiller TL;Chen S;Klein AP;Pardoll DM;Topalian SL;Chen L
通讯作者：
Chen L
影响因子：
28.4
作者：
Gaule P;Smithy JW;Toki M;Rehman J;Patell-Socha F;Cougot D;Collin P;Morrill P;Neumeister V;Rimm DL
通讯作者：
Rimm DL
影响因子：
64.8
作者：
Herbst RS;Soria JC;Kowanetz M;Fine GD;Hamid O;Gordon MS;Sosman JA;McDermott DF;Powderly JD;Gettinger SN;Kohrt HE;Horn L;Lawrence DP;Rost S;Leabman M;Xiao Y;Mokatrin A;Koeppen H;Hegde PS;Mellman I;Chen DS;Hodi FS
通讯作者：
Hodi FS
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM