Department of Urology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.
Department of Pathology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.
Virchows Arch. 2021 Oct;479(4):705-713. doi: 10.1007/s00428-021-03094-6. Epub 2021 Apr 28.
Urothelial bladder cancer (UBC) patients ineligible to platinum-based chemotherapy can be treated with immune-checkpoint inhibitors (ICI) in Programmed Death Ligand 1 (PD-L1) positive cases. Although concordance exists between different PD-L1 assays, little is known on PD-L1 expression variability in matched UBC samples. We compared PD-L1 expression in whole slides of matched transurethral resections (TURBT), radical cystectomies (RC), and lymph node metastasis (LN). Immunohistochemistry using the VENTANA PD-L1 (SP263) assay was performed on 115 patients and scored positive if expression occurred in ≥25% immune cells (IC), ≥25% tumour cells (TC), or both. PD-L1 was positive in 42.7% TURBT, 39.8% RC, and 27.3% LN specimens. Concordance was moderate (κ=0.52; P<0.001) between TURBT and RC, and fair between LN and TURBT (κ=0.31; P=0.048) or RC (κ=0.25; P=0.075). Comparison with the VENTANA PD-L1 (SP142) assay which had been performed previously on the same cohort showed moderate to substantial inter-assay agreement (κ=0.42-0.66). Although TC staining is not part of the SP142 scoring algorithm, discordant PD-L1 assay outcome could be attributed to SP263 TC≥25% staining in only 41% of cases. These results show that PD-L1 expression variability between matched specimens is higher than that between individual assays. Optimal specimen determination for PD-L1 testing needs to be addressed in future studies.
尿路上皮膀胱癌（UBC）患者不符合铂类化疗条件的，可以在 PD-L1 阳性病例中使用免疫检查点抑制剂（ICI）进行治疗。虽然不同的 PD-L1 检测方法之间存在一致性，但对于匹配的 UBC 样本中 PD-L1 表达的变异性知之甚少。我们比较了匹配的经尿道膀胱肿瘤切除术（TURBT）、根治性膀胱切除术（RC）和淋巴结转移（LN）的整块切片中的 PD-L1 表达。对 115 例患者进行了 VENTANA PD-L1（SP263）检测的免疫组化检测，如果≥25%的免疫细胞（IC）、≥25%的肿瘤细胞（TC）或两者均有表达，则为阳性。TURBT、RC 和 LN 标本中 PD-L1 阳性率分别为 42.7%、39.8%和 27.3%。TURBT 与 RC 之间的一致性为中度（κ=0.52；P<0.001），而 LN 与 TURBT（κ=0.31；P=0.048）或 RC（κ=0.25；P=0.075）之间的一致性为一般。与之前在同一队列中进行的 VENTANA PD-L1（SP142）检测进行比较显示，两种检测方法之间具有中度至高度的一致性（κ=0.42-0.66）。尽管 TC 染色不是 SP142 评分算法的一部分，但在只有 41%的情况下，SP263 TC≥25%染色可归因于 PD-L1 检测结果不一致。这些结果表明，匹配标本之间的 PD-L1 表达变异性高于单个检测方法之间的变异性。未来的研究需要确定 PD-L1 检测的最佳标本。
