Ahn Soomin, Woo Ji Won, Kim Hyojin, Cho Eun Yoon, Kim Ahrong, Kim Jee Yeon, Kim Chungyeul, Lee Hee Jin, Lee Ji Shin, Bae Young Kyung, Kwon Youngmee, Kim Wan Seop, Park So Yeon
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
J Breast Cancer. 2021 Jun;24(3):266-279. doi: 10.4048/jbc.2021.24.e29. Epub 2021 May 26.
The programmed death ligand 1 (PD-L1) SP142 assay with a 1% immune cell (IC) cutoff is approved for the selection of advanced triple-negative breast cancer (TNBC) patients for atezolizumab treatment. We aimed to evaluate the interobserver concordance of PD-L1 scoring and inter-assay variability of various PD-L1 assays in TNBC.
Thirty patients with primary TNBC were selected, and SP142, SP263, 22C3, and E1L3N assays were performed. PD-L1 staining in ICs and tumor cells (TCs) was scored by 10 pathologists who were blinded to the assay. The interobserver concordance among pathologists and the inter-assay variability of the four PD-L1 assays were analyzed. For SP142, the intraobserver concordance among the six pathologists was analyzed after training.
The adjusted means of PD-L1 IC scoring ranged from 6.2% to 12.9% for the four assays; the intraclass correlations showed moderate (0.584-0.649) reader concordance. The PD-L1 IC scoring with a 1% cutoff resulted in identical scoring in 40.0%-66.7% of cases and a poor to moderate agreement (Fleiss κ statistic [FKS] = 0.345-0.534) for the four assays. The SP142 assay had the widest range of positive rate (56.5%-100.0%), lowest number of cases with identical scoring, and lowest FKS at 1% cutoff. Pairwise comparison of adjusted means showed significantly decreased PD-L1 staining in SP142 compared with the other assays in both ICs and TCs. As for the intraobserver concordance in the SP142 assay, the overall percent agreement was 87.8% with a 1% IC cutoff. After training, the proportion of cases with identical scoring at a 1% IC cutoff increased to 70.0%; the FKS also increased to 0.610.
The concordance of PD-L1 IC scoring among pathologists was low, at the 1% cutoff for the SP142 assay without training. SP142 showed the lowest PD-L1 expression in both IC and TC.
程序性死亡配体1（PD-L1）SP142检测以1%免疫细胞（IC）为临界值，已被批准用于筛选晚期三阴性乳腺癌（TNBC）患者接受阿替利珠单抗治疗。我们旨在评估TNBC中PD-L1评分的观察者间一致性以及各种PD-L1检测方法的检测间变异性。
选取30例原发性TNBC患者，进行SP142、SP263、22C3和E1L3N检测。10名对检测方法不知情的病理学家对IC和肿瘤细胞（TC）中的PD-L1染色进行评分。分析病理学家之间的观察者间一致性以及四种PD-L1检测方法的检测间变异性。对于SP142，在培训后分析6名病理学家的观察者内一致性。
四种检测方法的PD-L1 IC评分调整均值在6.2%至12.9%之间；组内相关性显示读者一致性为中等（0.584 - 0.649）。以1%为临界值的PD-L1 IC评分在40.0% - 66.7%的病例中得出相同评分，四种检测方法的一致性为差到中等（Fleiss κ统计量[FKS]=0.345 - 0.534）。SP142检测的阳性率范围最广（56.5% - 100.0%），相同评分的病例数最少，在1%临界值时FKS最低。调整均值的两两比较显示，与其他检测方法相比，SP142在IC和TC中的PD-L1染色均显著降低。至于SP142检测中的观察者内一致性，以1% IC为临界值时总体一致率为87.8%。培训后，以1% IC为临界值时相同评分的病例比例增至70.0%；FKS也增至0.610。
在未经培训的情况下，对于SP142检测，以1%为临界值时，病理学家之间PD-L1 IC评分的一致性较低。SP142在IC和TC中均显示出最低的PD-L1表达。
