Oncology Companion Diagnostics Unit, Precision Medicine, R&D Oncology, AstraZeneca, Cambridge, UK.
Diagnostic Development Unit, Precision Medicine, R&D Oncology, AstraZeneca, Cambridge, UK.
Diagn Pathol. 2019 Sep 2;14(1):99. doi: 10.1186/s13000-019-0873-6.
Antibodies targeting the programmed cell death-1 (PD-1)/PD-ligand 1 (PD-1/PD-L1) checkpoint have shown promising clinical activity in patients with advanced urothelial carcinoma (UC). Expression of PD-L1 in UC tumors has been investigated using different antibody clones, staining protocols, and scoring algorithms. The aim was to establish the extent of concordance among PD-L1 immunohistochemistry (IHC) assays.
Tumor biopsy samples (N = 335) were assessed using four commercially available PD-L1 assays: VENTANA SP263, VENTANA SP142, PD-L1 IHC 28-8 pharmDx, and PD-L1 IHC 22C3 pharmDx. PD-L1 analytical staining and classification concordance, including agreement between clinically relevant scoring algorithms, were investigated using overall/positive/negative percentage agreement (OPA/PPA/NPA).
Good analytical correlation was observed among the VENTANA SP263, PD-L1 IHC 22C3 pharmDx, and PD-L1 IHC 28-8 pharmDx assays for tumor cell (TC) and immune cell (IC) PD-L1 staining with Spearman rank coefficients of 0.92-0.93 for TCs and 0.88-0.91 for ICs. However, concordance (preset criterion: ≥85%) between patient PD-L1 status when applying the TC or IC ≥ 25% (VENTANA SP263) cutoff was only achieved for PD-L1 IHC 22C3 pharmDx versus VENTANA SP263 (OPA 92.2%, PPA 86.4%, NPA 95.4%). Differences were observed between patient populations with UC tumors classified as PD-L1 high versus PD-L1 low/negative using combined positive score (CPS) ≥1, CPS ≥10, IC ≥5%, and TC/IC ≥25%.
The VENTANA SP263 and PD-L1 IHC 22C3 pharmDx assays are analytically similar in UC. When the different PD-L1 assays were combined with their specified clinical scoring algorithms, differences were seen in patient classification driven by substantial differences in scoring approaches.
针对程序性细胞死亡-1（PD-1）/PD-配体 1（PD-1/PD-L1）检查点的抗体在晚期尿路上皮癌（UC）患者中显示出有希望的临床活性。已经使用不同的抗体克隆、染色方案和评分算法研究了 UC 肿瘤中 PD-L1 的表达。目的是确定 PD-L1 免疫组织化学（IHC）检测之间的一致性程度。
使用四种市售的 PD-L1 检测方法评估肿瘤活检样本（N=335）：VENTANA SP263、VENTANA SP142、PD-L1 IHC 28-8 pharmDx 和 PD-L1 IHC 22C3 pharmDx。使用总/阳性/阴性百分比一致性（OPA/PPA/NPA）研究了 PD-L1 分析染色和分类一致性，包括临床相关评分算法之间的一致性。
在 VENTANA SP263、PD-L1 IHC 22C3 pharmDx 和 PD-L1 IHC 28-8 pharmDx 检测中，肿瘤细胞（TC）和免疫细胞（IC）PD-L1 染色观察到良好的分析相关性，TC 的 Spearman 秩系数为 0.92-0.93，IC 的 Spearman 秩系数为 0.88-0.91。然而，当应用 TC 或 IC≥25%（VENTANA SP263）截点时，患者 PD-L1 状态的一致性（预设标准：≥85%）仅在 PD-L1 IHC 22C3 pharmDx 与 VENTANA SP263 之间达成（OPA 92.2%，PPA 86.4%，NPA 95.4%）。在使用组合阳性评分（CPS）≥1、CPS≥10、IC≥5%和 TC/IC≥25%将 UC 肿瘤分为 PD-L1 高与 PD-L1 低/阴性的患者人群之间观察到差异。
在 UC 中，VENTANA SP263 和 PD-L1 IHC 22C3 pharmDx 检测在分析上相似。当不同的 PD-L1 检测与特定的临床评分算法结合使用时，由于评分方法的显著差异，在患者分类方面存在差异。
