Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies
Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies
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DOI：
10.1093/annonc/mdv489
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发表时间：
2016-01-01
影响因子：
50.5
通讯作者：
Hofman, P.
中科院分区：
文献类型：
--
作者：
Ilie, M.;Long-Mira, E.;Hofman, P.
肿瘤细胞（TC）和/或肿瘤浸润免疫细胞（IC）上程序性死亡配体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）患者的高缓解率相关。使用PD-L1免疫组织化学（IHC）测试来确定对免疫疗法的反应性已经提出了与相应的切除的手术标本相比，其在肺活检中评估的可靠性和再现性的问题。在160名患有可手术NSCLC的患者中，在整个手术组织切片和匹配的肺活检中评估了TC和IC中的PD-L1表达，通过使用高灵敏度的SP142 IHC测定。根据PD-L1表达的增加，将标本评分为TC 0-3和IC 0-3 JD-L1表达在手术切除和匹配的活检标本之间经常不一致（总体不一致率= 48%; 95%置信区间4.64-13.24），Kappa值等于0.218（较差一致性）。在所有情况下，活检标本低估了在整个组织样本中观察到的PD-L1状态。在切除标本中，PD-L1阳性IC肿瘤比PD-L1阳性TC肿瘤更常见。这种差异主要与匹配活检组织中PD-L1阳性IC成分的缺乏有关。我们的研究结果表明，肺活检组织和相应切除肿瘤之间TC和IC中PD-L1表达的相关性相对较差。尽管这些结果需要在更大的队列中进一步验证，但它们表明诊断性活检中PD-L1表达的日常评价在定义PD-L1靶向治疗的敏感性时可能会产生误导。
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 kappa 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.