Paliogiannis Panagiotis, Lobrano Renato, Bella Michele Angelo, Fara Antonella, Uras Maria Gabriela, Pinna Maria Antonia, Tedde Alessandro, Madonia Massimo, Zinellu Angelo, Cossu Antonio
Unit of Anatomic Pathology and Histology, University Hospital of Sassari (A.O.U. SS), Sassari, Italy; Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy.
Division of Pathology, European Institute of Oncology IRCCS, 20141 Milan, Italy.
Ann Diagn Pathol. 2024 Apr;69:152267. doi: 10.1016/j.anndiagpath.2024.152267. Epub 2024 Jan 20.
Programmed death ligand 1 (PD-L1) is currently the only biomarker used for the selection of patients with bladder urothelial cancer for immunotherapy. Several platforms, antibodies and scores are currently available for the evaluation of the expression of PD-L1 in immunohistochemistry (IHC). In this study three different antibodies (SP263, SP142 and 22C3) were compared to establish their performances and concordance rates. Twenty-four consecutive cases of surgically resected urothelial cancers of the bladder were enrolled. All cases were revised, and appropriate tumor areas were selected for IHC. Three commercially available PD-L1 antibodies were tested: 22C3 pharmDx with Dako Autostainer Link 48 (Dako, Carpinteria, Ca), and SP263 and SP142 with the Ventana BenchMark (Ventana Medical Systems, Tucson, AZ) platform. All slides were evaluated by an expert pathologist and both the tumor proportion score (TPS) and the combined positive score (CPS) were determined and compared at two different cut-off levels (≥ 1 and ≥ 10). The SP263 and 22C3 clones produced more positive results with the CPS and TPS scores, respectively. The CPS score identified more positive cases than the TPS score, irrespectively of the clone or the cut-off used; the difference was statistically significant in both the SP263 and SP142 clones with the ≥1 cut-off. No statistically significant differences were found between the clones when the ≥1 cut-off was used, irrespectively of the score. At the contrary, a statistically significant difference (p = 0.024) and a trend to significance (p = 0.082) were respectively found for the TPS and CPS scores, when the SP22C3 and the SP142 clones were compared at a cut-off level of ≥10. The ICC test using CPS was 0.676 and 0.578 for the ≥1 and ≥ 10 cut-offs respectively, and 0.729 and 0.467 respectively for the same cut-offs using TPS. This suggests that the three antibodies under investigation cannot be used interchangeably, especially the 22C3 and SP142 clones which showed statistically significant difference when TPS was tested at a ≥ 10 cut-off.
程序性死亡配体1（PD-L1）是目前唯一用于筛选膀胱尿路上皮癌患者进行免疫治疗的生物标志物。目前有几种平台、抗体和评分可用于评估免疫组织化学（IHC）中PD-L1的表达。在本研究中，比较了三种不同的抗体（SP263、SP142和22C3），以确定它们的性能和一致性率。纳入了24例连续手术切除的膀胱尿路上皮癌病例。对所有病例进行复查，并选择合适的肿瘤区域进行免疫组化检测。测试了三种市售的PD-L1抗体：使用Dako Autostainer Link 48（Dako，加利福尼亚州卡平特里亚）的22C3 pharmDx，以及使用Ventana BenchMark（Ventana Medical Systems，亚利桑那州图森）平台的SP263和SP142。所有切片均由一位专家病理学家进行评估，并在两个不同的临界值水平（≥1和≥10）下确定并比较肿瘤比例评分（TPS）和综合阳性评分（CPS）。SP263和22C3克隆分别在CPS和TPS评分中产生了更多的阳性结果。无论使用何种克隆或临界值，CPS评分识别出的阳性病例均多于TPS评分；在临界值≥1时，SP263和SP142克隆中的差异均具有统计学意义。当使用临界值≥1时，无论评分如何，各克隆之间均未发现统计学显著差异。相反，当在临界值≥10时比较SP22C3和SP142克隆时，TPS和CPS评分分别发现有统计学显著差异（p = 0.024）和显著趋势（p = 0.082）。使用CPS进行的ICC测试在临界值≥1和≥10时分别为0.676和0.578，使用TPS进行相同临界值测试时分别为0.729和0.467。这表明所研究的三种抗体不能互换使用，特别是22C3和SP142克隆，当在临界值≥10时测试TPS时，它们显示出统计学显著差异。
