Institute of Pathology, Technische Universität München, Trogerstr. 18, 81675, Munich, Germany.
Roche Pharma AG, Grenzach-Wyhlen, Germany.
Virchows Arch. 2019 Nov;475(5):599-608. doi: 10.1007/s00428-019-02610-z. Epub 2019 Jul 2.
Programmed death-ligand 1 (PD-L1) expression on tumor cells (TC) or tumor-infiltrating immune cells (IC) correlated in several studies with PD-L1/programmed death-1 (PD-1) checkpoint inhibitor efficacy. Since June 2018, a positive PD-L1 status is required for atezolizumab or pembrolizumab treatment of patients with advanced or metastasized urothelial bladder cancer, who are ineligible for cisplatin-containing therapy. We examined technical comparability and inter-reader agreement of four clinically developed PD-L1 assays in locally advanced disease. Archived, formalin-fixed, paraffin-embedded sections from 30 patients (73.3% cystectomies, 26.7% transurethral resections) were stained by PD-L1 immunohistochemistry using VENTANA SP142, VENTANA SP263, DAKO 22C3, and DAKO 28-8 at two sites per manufacturers' protocols and scored blinded at five sites for PD-L1 expression on IC (% per tumor area) and TC (%). Small, non-significant inter-assay differences were observed for IC. For TC, SP142 showed significantly lower staining percentages. Pairwise comparisons revealed - 0.3 to 1.6% differences in adjusted means between assays for IC, and for TC, - 10.5 to - 7.8% (SP142 versus others) and - 1.9 to 2.7% (other comparisons). Inter-reader and inter-assay agreement was moderate to high for both IC and TC. Allocation to binary cutoffs (1%, 5%, 10%) showed substantial to high Kappa agreement scores (0.440-0.923) for IC and TC between assays for each reader. This first multicenter study, with five independent readers blinded with respect to the assay used, suggests that all four currently clinically relevant assays are analytically similar for evaluation of PD-L1-stained IC and three (SP263, 22C3, and 28-8) for PD-L1-stained TC. Inter-observer agreement for trained readers in scoring of both IC and TC positivity was generally high.
肿瘤细胞 (TC) 或肿瘤浸润免疫细胞 (IC) 上的程序性死亡配体 1 (PD-L1) 表达在几项研究中与 PD-L1/程序性死亡-1 (PD-1) 检查点抑制剂的疗效相关。自 2018 年 6 月以来，对于不适合含顺铂治疗的晚期或转移性尿路上皮膀胱癌患者，需要使用阿特珠单抗或 pembrolizumab 进行治疗，且患者的 PD-L1 状态需为阳性。我们检测了四种临床上开发的 PD-L1 检测方法在局部晚期疾病中的技术可比性和多位读者的一致性。使用 VENTANA SP142、 VENTANA SP263、 DAKO 22C3 和 DAKO 28-8 对 30 名患者（73.3%的膀胱切除术，26.7%的经尿道切除术）的存档、福尔马林固定、石蜡包埋切片进行了 PD-L1 免疫组化染色，根据制造商的方案在每个部位进行两次染色，并在五个部位对 IC（肿瘤面积百分比）和 TC（%）的 PD-L1 表达进行盲法评分。IC 观察到小的、无显著意义的检测间差异。对于 TC，SP142 显示出明显较低的染色百分比。配对比较显示，IC 之间的检测调整均值差异为 -0.3 至 1.6%，TC 之间的差异为 -10.5 至 -7.8%（SP142 与其他检测方法）和 -1.9 至 2.7%（其他比较）。对于 IC 和 TC，两位读者之间的组内和检测间的一致性为中至高。对于每个读者，对于 IC 和 TC，所有四种目前临床上相关的检测方法在二进制截止值（1%、5%、10%）的分配上均显示出中等至高的 Kappa 一致性评分（0.440-0.923）。这是第一项多中心研究，五位独立的读者在评估使用的检测方法方面均处于盲态，这表明目前临床上有四种相关检测方法在评估 PD-L1 染色的 IC 方面具有分析相似性，对于 PD-L1 染色的 TC，三种检测方法（SP263、22C3 和 28-8）也具有分析相似性。对于 IC 和 TC 阳性评分，受过训练的读者之间的观察者间一致性通常较高。
