Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice IRCAN Team 3, INSERM U1081/UMR CNRS 7284, Faculty of Medicine of Nice, University of Nice Sophia Antipolis, Nice.
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice.
Ann Oncol. 2016 Jan;27(1):147-53. doi: 10.1093/annonc/mdv489. Epub 2015 Oct 19.
High expression of programmed death ligand-1 (PD-L1) on tumor cells (TC) and/or on tumor-infiltrating immune cells (IC) is associated with a high response rate in patients with advanced nonsmall-cell lung cancer (NSCLC) treated with PD-L1 inhibitors. The use of a PD-L1 immunohistochemical (IHC) test in determining the responsiveness to immunotherapy has raised the question of the reliability and reproducibility of its evaluation in lung biopsies compared with corresponding resected surgical specimens.
PD-L1 expression in TC and IC was assessed in 160 patients with operable NSCLC on both whole surgical tissue sections and matched lung biopsies, by using a highly sensitive SP142 IHC assay. The specimens were scored as TC 0-3 and IC 0-3 based on increasing PD-L1 expression.
PD-L1 expression was frequently discordant between surgical resected and matched biopsy specimens (the overall discordance rate = 48%; 95% confidence interval 4.64-13.24) and κ value was equal to 0.218 (poor agreement). In all cases, the biopsy specimens underestimated the PD-L1 status observed on the whole tissue sample. PD-L1-positive IC tumors were more common than PD-L1-positive TC tumors on resected specimens. The discrepancies were mainly related to the lack of a PD-L1-positive IC component in matched biopsies.
Our results indicate relatively poor association of the PD-L1 expression in TC and IC between lung biopsies and corresponding resected tumors. Although these results need to be further validated in larger cohorts, they indicate that the daily routine evaluation of the PD-L1 expression in diagnostic biopsies can be misleading in defining the sensitivity to treatment with PD-L1 targeted therapy.
肿瘤细胞（TC）和/或肿瘤浸润免疫细胞（IC）中程序性死亡配体-1（PD-L1）的高表达与接受 PD-L1 抑制剂治疗的晚期非小细胞肺癌（NSCLC）患者的高反应率相关。在确定免疫治疗反应性时使用 PD-L1 免疫组织化学（IHC）检测引发了一个问题，即与相应的切除手术标本相比，其在肺活检中的评估的可靠性和可重复性。
使用高度敏感的 SP142 IHC 检测，评估了 160 名可手术 NSCLC 患者的整个手术组织切片和匹配的肺活检标本中的 TC 和 IC 的 PD-L1 表达。根据 PD-L1 表达的增加，将标本评分 TC0-3 和 IC0-3。
手术切除和匹配活检标本之间的 PD-L1 表达经常不一致（总体不一致率=48%；95%置信区间 4.64-13.24），κ 值等于 0.218（一致性差）。在所有情况下，活检标本都低估了整个组织样本上观察到的 PD-L1 状态。在切除标本中，PD-L1 阳性 IC 肿瘤比 PD-L1 阳性 TC 肿瘤更为常见。这些差异主要与匹配活检中缺乏 PD-L1 阳性 IC 成分有关。
我们的结果表明，肺活检和相应切除肿瘤中 TC 和 IC 之间的 PD-L1 表达相关性相对较差。尽管这些结果需要在更大的队列中进一步验证，但它们表明，在诊断性活检中常规评估 PD-L1 表达可能会误导对 PD-L1 靶向治疗敏感性的定义。
