可靠、可重复的方法来解读肿瘤细胞（TC）和免疫细胞（IC）上的程序性死亡配体-1（PD-L1）表达是病理学家为与检查点抑制剂治疗相关的决策提供帮助所需要的。我们的国际研究在标准化条件下比较了使用联合阳性评分（CPS）评估PD-L1表达的病理医生间的协议，在这些条件下，样本来自胃/胃食管结合/食管腺癌的患者。使用PD-L1 IHC 28-8和22C3（Agilent）pharmDx免疫组化检测方法，单一实验室对100例预处理的腺癌活检标本进行了染色。12名病理学家在Agilent的CPS培训课程之前和之后，使用这些活检标本的整个扫描图像评估PD-L1 CPS。此外，病理学家以单一组织片段为基础，确定了100个活检样本中的35个样本的PD-L1阳性TC、IC和总体使细胞。评分协议使用ICC（组间相关系数）进行评估。对于100个活检标本的CPS的观察者间可变性高，病理医生之间的协议只有公平一致（0.45至0.55）和训练后（0.56至0.57），两种检测方法都是如此。对于这35个单一活检样本，也观察到了可变性/公平一致性，包括总活的TC数量（ICC 0.09）、PD-L1阳性IC数量（ICC 0.19）、PD-L1阳性TC数量（ICC 0.54）和计算的CPS（ICC 0.14），而计算的TC评分（阳性TC/总TC）呈现优良一致性（ICC 0.82）。最差的病理医生间协议的样本的回顾性组织学检查显示出（1）阳性染色间质细胞的不明确鉴定，（2）染色的淡或变化强度，（3）难以区分膜性和胞浆性肿瘤染色，以及（4）烧结和压碎伪影等可能混淆因素。这些结果强调了需要客观技术标准化PD-L1表达的解读方法，使用CPS方法对胃/胃食管结合癌活检进行评估，以准确识别最有可能从免疫检查点抑制剂治疗中获益的患者。版权所有©2023 Elsevier Inc.发表。

Reliable, reproducible methods to interpret programmed death ligand-1 (PD-L1) expression on tumor cells (TC) and immune cells (IC) are needed for pathologists to inform decisions associated with checkpoint inhibitor therapies. Our international study compared interpathologist agreement of PD-L1 expression using combined positive score (CPS) under standardized conditions on samples from patients with gastric/gastroesophageal junction/esophageal adenocarcinoma. Tissue sections from 100 adenocarcinoma pre-treatment biopsies were stained in a single laboratory using the PD-L1 IHC 28-8 and 22C3(Agilent) pharmDx immunohistochemical assays. PD-L1 CPS was evaluated by 12 pathologists on scanned whole slide images of these biopsies before and after a 2-hour CPS training session by Agilent. Additionally, pathologists determined PD-L1 positive TC, IC, and total viable TC on a single tissue fragment from 35 of 100 biopsy samples. Scoring agreement among pathologists was assessed using the intraclass correlation coefficient (ICC). Interobserver variability for CPS for 100 biopsies was high with only fair agreement among pathologists both pre- (range 0.45 to 0.55) and post-training (range 0.56 to 0.57) for both assays. For the 35 single biopsy samples, poor/fair agreement was also observed for the total number viable TC (ICC 0.09), number of PD-L1 positive IC (ICC 0.19), number of PD-L1 positive TC (ICC 0.54), and calculated CPS (ICC 0.14), while calculated TC score (positive TC/Total TC) showed excellent agreement (ICC 0.82). Retrospective histologic review of samples with the poorest interpathologist agreement revealed (1) ambiguous identification of positively staining stromal cells, (2) faint or variable intensity of staining, (3) difficulty in distinguishing membranous from cytoplasmic tumor staining, and (4) cautery and crush artifact, as possible confounding factors. These results emphasize the need for objective techniques to standardize the interpretation of PD-L1 expression when using the CPS methodology on gastric/gastroesophageal junction cancer biopsies to accurately identify patients most likely to benefit from immune checkpoint inhibitor therapy.Copyright © 2023. Published by Elsevier Inc.