Sommer Ulrich, Eckstein Markus, Ammann Johannes, Braunschweig Till, Macher-Göppinger Stephan, Schwamborn Kristina, Hieke-Schulz Stefanie, Harlow Greg, Flores Mike, Wullich Bernd, Wirth Manfred, Roth Wilfried, Knüchel Ruth, Weichert Wilko, Baretton Gustavo, Hartmann Arndt
Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Clin Genitourin Cancer. 2020 Oct;18(5):e629-e642. doi: 10.1016/j.clgc.2020.02.009. Epub 2020 Feb 15.
Previous studies have suggested increased clinical benefit with inhibition of programmed death-ligand 1 (PD-L1)/programmed death-1 in patients with PD-L1-positive locally advanced/metastatic renal cell carcinoma (RCC). We examined the analytical and inter-observer comparability of PD-L1-positivity across 4 clinically developed immunohistochemistry assays in clear-cell RCC (CCRCC).
Randomly selected archived, formalin-fixed, paraffin-embedded nephrectomy specimens from 201 patients with locally advanced CCRCC were screened using VENTANA SP142. From these, 30 cases were selected based on their tumor-infiltrating immune cell (IC) PD-L1 status (PD-L1-IC-positivity of < 1%, 1%-5%, or > 5%; 10 cases each). These cases were stained for PD-L1 using VENTANA SP142 and SP263, and DAKO 22C3 and 28-8, and scored for PD-L1 expression on IC and tumor cells (TC) by trained readers at 5 sites.
Adjusted mean percentages of PD-L1-IC-positivity and PD-L1-TC-positivity varied from 4.0% to 4.9% and from 1.3% to 10.7%, respectively, between assays. Inter-assay differences in PD-L1-IC-positivity were small and non-significant (P = .1938 to .9963); for PD-L1-TC-positivity, significant differences were observed between VENTANA SP142 and the other assays (P ≤ .0001) and between VENTANA SP263 and DAKO 28-8 (P = .0248). Intra-class correlation values showed moderate-to-high inter-reader agreement for each assay for PD-L1-IC-positivity and for 3 assays for PD-L1-TC-positivity.
In this first multicenter analytical comparison study of PD-L1 assays in CCRCC, PD-L1-positivity could be assessed reproducibly using all 4 assays for IC and for 3 of the 4 assays for TC.
既往研究表明，在程序性死亡配体1（PD-L1）/程序性死亡1阳性的局部晚期/转移性肾细胞癌（RCC）患者中，抑制PD-L1/程序性死亡1可带来更大的临床获益。我们在透明细胞肾细胞癌（CCRCC）中，检测了4种临床应用的免疫组化检测方法对PD-L1阳性的分析及观察者间可比性。
使用VENTANA SP142对随机选取的201例局部晚期CCRCC患者的存档福尔马林固定石蜡包埋肾切除标本进行筛查。从中，根据肿瘤浸润免疫细胞（IC）的PD-L1状态（PD-L1-IC阳性率<1%、1%-5%或>5%；各10例）选取30例病例。这些病例使用VENTANA SP142和SP263以及DAKO 22C3和28-8进行PD-L1染色，并由5个机构的专业阅片者对IC和肿瘤细胞（TC）上的PD-L1表达进行评分。
各检测方法之间，PD-L1-IC阳性率和PD-L1-TC阳性率的校正平均百分比分别在4.0%至4.9%和1.3%至10.7%之间。PD-L1-IC阳性率的检测方法间差异较小且无统计学意义（P = 0.1938至0.9963）；对于PD-L1-TC阳性率，VENTANA SP142与其他检测方法之间（P≤0.0001）以及VENTANA SP263与DAKO 28-8之间（P = 0.0248）观察到显著差异。组内相关值显示，对于PD-L1-IC阳性率，每种检测方法的阅片者间一致性为中度至高度，对于PD-L1-TC阳性率，4种检测方法中的3种阅片者间一致性为中度至高度。
在这项CCRCC中PD-L1检测方法的首个多中心分析比较研究中，使用所有4种检测方法检测IC以及4种检测方法中的3种检测TC时，均可重复性地评估PD-L1阳性。
