Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Division of Pathology, IEO, European Institute of Oncology IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Hum Pathol. 2024 Feb;144:22-27. doi: 10.1016/j.humpath.2024.01.008. Epub 2024 Jan 24.
PD-L1 test is recommended in different types of tumors to select patients eligible for immune checkpoint inhibitors (ICI) therapy. Several factors make this test challenging in metastatic triple-negative breast cancer (mTNBC). Different assays and platforms are available, each associated with distinct scoring systems and threshold values specific to the ICI compound used, i.e. CPS≥10 for pembrolizumab and IC ≥ 1 % for atezolizumab. Our objective was to assess the consistency of PD-L1 testing in mTNBC by examining interobserver and interassay reproducibility. We assessed n = 60 mTNBC samples for PD-L1 testing using 22C3 pharmDx assay on a Dako Autostainer Link 48 and VENTANA PD-L1 (SP263) on a Ventana BenchMark Ultra. Additionally, a subset of n = 19 samples was tested using the SP142 assay, also on the Ventana BenchMark Ultra. CPS with both 22C3 and SP263 was independently evaluated by five pathologists, all certified PD-L1 trainers. The IC with SP142 was assessed by three of these pathologists, who have particular expertise in breast pathology. Following the computation of the intraclass correlation coefficient (ICC) for each assay and their respective thresholds, we assessed the agreement between different raters and assays using Fleiss's κ, with a 95 % confidence interval (CI). Overall, we observed a significant (p < 0.001) ICC with both CPS assays [22C3 = 0.939 (CI:0.913-0.96); SP263 = 0.972 (CI:0.96-0.982); combined 22C3-SP263 = 0.909 (CI:0.874-0.938)]. Fleiss's κ confirmed an almost perfect agreement among pathologists and assays: 22C3 = 0.938 (CI:0.857-1.018); SP263 = 0.972 (CI:0.890-1.052); combined 22C3-SP263 = 0.907 (CI:0.869-0.945). Perfect inter-rater agreement was reached considering IC. This study establishes the reliability of assessing CPS in mTNBC using either the 22C3 pharmDx, as employed in the KEYNOTE studies, or the VENTANA SP263 assay. Each assay must be used on its designated platform, namely the Dako for 22C3 pharmDx and the Ventana for VENTANA SP263. It is important to remark that CPS and IC identify different patient cohorts and, therefore, are not interchangeable.
PD-L1 检测被推荐用于不同类型的肿瘤，以选择适合免疫检查点抑制剂（ICI）治疗的患者。在转移性三阴性乳腺癌（mTNBC）中，有几个因素使得该检测具有挑战性。目前有多种不同的检测方法和平台，每种方法都有特定的评分系统和阈值，与所使用的 ICI 化合物有关，即帕博利珠单抗的 CPS≥10，阿替利珠单抗的 IC≥1%。我们的目的是通过评估 mTNBC 中 PD-L1 检测的观察者间和检测间的可重复性，来评估 PD-L1 检测的一致性。我们使用 22C3 pharmDx 检测法（在 Dako Autostainer Link 48 上）和 VENTANA PD-L1（SP263）（在 Ventana BenchMark Ultra 上）对 60 例 mTNBC 样本进行了 PD-L1 检测。此外，一组 n=19 例样本使用 SP142 检测法（也在 Ventana BenchMark Ultra 上）进行了检测。五位病理学家对 22C3 和 SP263 的 CPS 进行了独立评估，这五位病理学家均为 PD-L1 培训认证专家。其中三位病理学家使用 SP142 评估了 IC，他们在乳腺病理学方面具有特别的专业知识。在计算了每个检测方法及其各自的阈值的组内相关系数（ICC）后，我们使用 Fleiss's κ 评估了不同评估者和检测方法之间的一致性，置信区间（CI）为 95%。总体而言，我们观察到两种 CPS 检测方法均具有显著的（p<0.001）ICC [22C3=0.939（CI：0.913-0.96）；SP263=0.972（CI：0.96-0.982）；22C3-SP263 联合=0.909（CI：0.874-0.938）]。Fleiss's κ 证实了病理学家和检测方法之间几乎完全一致的协议：22C3=0.938（CI：0.857-1.018）；SP263=0.972（CI：0.890-1.052）；22C3-SP263 联合=0.907（CI：0.869-0.945）。考虑到 IC，评估者之间达到了完美的一致性。这项研究确立了使用 22C3 pharmDx（在 KEYNOTE 研究中使用）或 VENTANA SP263 检测法评估 mTNBC 中 CPS 的可靠性。每种检测方法都必须在其指定的平台上使用，即 22C3 pharmDx 在 Dako 上，VENTANA SP263 在 Ventana 上。需要注意的是，CPS 和 IC 确定了不同的患者群体，因此不能互换使用。
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