N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia.
N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia.
Ann Diagn Pathol. 2022 Aug;59:151968. doi: 10.1016/j.anndiagpath.2022.151968. Epub 2022 May 6.
PD-L1 testing is currently performed by immunohistochemistry (IHC). We questioned whether the results of PCR-based measurement of PD-L1 RNA expression correlate with IHC scores obtained by different commercial assays.
167 consecutive non-squamous non-small cell lung carcinomas (NSCLCs) were analyzed for PD-L1 RNA expression and 22C3, SP263, and SP142 IHC scoring using recommended cut-offs. RNA expression was divided into low, moderate, and high categories.
RNA and protein expression demonstrated moderate correlation as continuous variables. Using prespecified RNA cut-offs, PCR testing showed a high negative predictive value towards the IHC analysis: the share of PD-L1 protein-negative tumors among cases classified as PD-L1-low by the PCR test reached 92-99% for all three antibodies. Meanwhile, about half of cases with moderate to high PD-L1 RNA expression had IHC staining in less than 1% tumor cells as determined by 22C3 or SP263 antibodies. Among the 51 discordant cases, which had <1% tumor staining by both 22C3 and SP263 clones but high RNA level, 29 (57%) showed ≥1% positive immune cells by SP263 and/or 22C3, 14 cases (27%) had detectable IHC expression in 0.1-0.9% tumor or immune cells by SP263 and/or 22C3, and 8 (16%) were entirely negative by IHC.
Some NSCLCs demonstrate readily detectable PD-L1 expression on the level of RNA, but fall below commonly accepted cut-offs by IHC. It remains to be studied whether these discrepancies are attributed to technical or biological reasons. Clinical sensitivity of these tumors to immune therapy deserves additional investigations.
PD-L1 检测目前通过免疫组织化学（IHC）进行。我们质疑基于 PCR 的 PD-L1 RNA 表达测量结果是否与通过不同商业检测获得的 IHC 评分相关。
分析了 167 例连续的非鳞状非小细胞肺癌（NSCLC）的 PD-L1 RNA 表达和 22C3、SP263 和 SP142 IHC 评分，使用了推荐的临界值。RNA 表达分为低、中、高三个类别。
RNA 和蛋白质表达作为连续变量显示出中等相关性。使用预设的 RNA 临界值，PCR 检测对 IHC 分析具有高阴性预测值：在所有三种抗体中，被 PCR 检测归类为 PD-L1 低的病例中，PD-L1 蛋白阴性肿瘤的比例达到 92-99%。与此同时，大约一半中等至高度 PD-L1 RNA 表达的病例，其 22C3 或 SP263 抗体检测的肿瘤细胞中免疫染色不到 1%。在 51 例不一致的病例中，22C3 和 SP263 克隆检测肿瘤染色均<1%，但 RNA 水平较高，其中 29 例（57%）SP263 和/或 22C3 检测到≥1%阳性免疫细胞，14 例（27%）SP263 和/或 22C3 检测到肿瘤或免疫细胞中 0.1-0.9%的可检测免疫表达，8 例（16%）IHC 完全阴性。
一些 NSCLC 表现出可检测的 RNA 水平上的 PD-L1 表达，但低于 IHC 通常接受的临界值。这些差异是由于技术还是生物学原因尚待研究。这些肿瘤对免疫治疗的临床敏感性值得进一步研究。
