Department of Pathology, Wexner Medical Center at The Ohio State University, Columbus, Ohio, USA.
Department of Pathology and Laboratory Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Diagn Cytopathol. 2021 Feb;49(2):219-225. doi: 10.1002/dc.24651. Epub 2020 Oct 26.
The evaluation of PD-L1 expression in nonsmall cell lung carcinoma (NSCLC) is becoming increasingly important given the effectiveness of PD-L1 inhibitors. Although cytologic specimens have been shown to be compatible with surgical specimens to evaluate PD-L1 immunohistochemistry (IHC), evidence of the reproducibility of PD-L1 in cytologic specimens is lacking. The aim of this study is to evaluate interobserver agreement in PD-L1 IHC in cytologic specimens.
PD-L1 IHC was performed on 86 NSCLC cytology specimens using Dako PD-L1 IHC 22C3 pharmDx. The digitally scanned whole slide images (WSI) were read by five pathologists. Each case was given a Tumor Proportion Score (TPS) and the results were compared between the observers. The interobserver concordance was assessed using 1% and 50% as cutoffs.
TPSs were highly correlated among observers (Spearman correlation coefficient, 0.86-0.94). Using greater than 1% as a cutoff, interobserver agreement measured by Fleiss Kappa was 0.74 for all pathologists and Cohen's Kappa coefficient ranged from 0.49 to 0.83, consistent with moderate to substantial agreement. With a cutoff of greater than 50%, Fleiss Kappa was 0.79 for all pathologists and the kappa values ranged from 0.63 to 0.90, consistent with substantial to almost perfect agreement. Several pitfalls were identified by reviewing discordant cases, including staining in macrophages, stromal cells, and intratumoral heterogeneity.
Our data suggest that TPS of PD-L1 IHC on cytology specimens is reproducible, with a better agreement when using 50% as the cutoff value. However, special attention is required when the TPS is near the 1% cutoff.
鉴于 PD-L1 抑制剂的有效性，非小细胞肺癌 (NSCLC) 中 PD-L1 表达的评估变得越来越重要。虽然细胞学标本已被证明与手术标本具有兼容性，可用于评估 PD-L1 免疫组化（IHC），但缺乏细胞学标本中 PD-L1 可重复性的证据。本研究旨在评估 PD-L1 IHC 在细胞学标本中的观察者间一致性。
使用 Dako PD-L1 IHC 22C3 pharmDx 在 86 例 NSCLC 细胞学标本上进行 PD-L1 IHC。五位病理学家对数字化扫描的全切片图像（WSI）进行了阅读。每个病例都给出了肿瘤比例评分（TPS），并比较了观察者之间的结果。使用 1%和 50%作为截止值来评估观察者间的一致性。
TPS 在观察者之间高度相关（Spearman 相关系数为 0.86-0.94）。使用大于 1%作为截止值，由 Fleiss Kappa 测量的观察者间一致性为所有病理学家的 0.74，Cohen's Kappa 系数范围为 0.49 至 0.83，一致为中度至高度一致。使用大于 50%的截止值时，所有病理学家的 Fleiss Kappa 为 0.79，kappa 值范围为 0.63 至 0.90，一致为高度至几乎完美一致。通过审查不一致的病例，确定了几个陷阱，包括巨噬细胞、基质细胞和肿瘤内异质性中的染色。
我们的数据表明，细胞学标本中 PD-L1 IHC 的 TPS 是可重复的，当使用 50%作为截止值时，一致性更好。但是，当 TPS 接近 1%的截止值时，需要特别注意。
