Comparison of 22C3 PD-L1 Expression between Surgically Resected Specimens and Paired Tissue Microarrays in Non-Small Cell Lung Cancer
Comparison of 22C3 PD-L1 Expression between Surgically Resected Specimens and Paired Tissue Microarrays in Non-Small Cell Lung Cancer
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DOI：
10.1016/j.jtho.2017.07.015
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发表时间：
2017-10-01
影响因子：
20.4
通讯作者：
Lin, Gen
中科院分区：
文献类型：
--
作者：
Li, Chao;Huang, Cheng;Lin, Gen
简介：肿瘤内程序性死亡配体1（PD-L1）表达的异质性导致配对样本之间PD-L1表达不一致的程度仍不清楚。在这里，PD-L1的状态，从NSCLC和相应的组织微阵列（TMA）作为替代biopsy specimens.Methods：PD-L1的表达进行了评估，22 C3免疫组化检测190档案手术标本和匹配的TMA结果之间的整个切片进行了比较。PD-L1表达通过肿瘤比例评分（TPS）确定，并分类为TPS低于1%，TPS为1%至49%，TPS为50%或更高。结果：PD-L1在肿瘤细胞上的表达百分比在个体TMA和匹配的手术标本之间差异很大。当采用PD-L1 TPS时，共观察到36/190例（18.9%）不一致病例，配对样本之间的x值为0.630。TMA分别低估或高估了36例匹配手术标本中的19例（52.8%）和36例匹配手术标本中的17例（47.2%）的PD-L1状态（p = 0.118）。PD-L1 TPS低于1%的病例的不一致率远低于TPS为1%至49%和TPS为50%或更高的病例（18.4% vs 56.7%和43.3%，p < 0.001）。当TPS为50%或更高作为临界值时，PD-L1 TPS小于50%的不一致率进一步降低至7.5%。这种差异主要是由于肿瘤内PD-L1表达的异质性以及与临床病理特征的无显著相关性。TMA中的PD-L1表达与相应手术标本中的PD-L1表达中度相关，表明在诊断性活检标本中评估PD-L1表达可能会误导对帕博利珠单抗治疗的敏感性，但作为排除PD患者的一种方法可能是可靠的。一线帕博利珠单抗治疗的L1 TPS低于50%。(C)2017年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
Introduction: The extent to which intratumoral heterogeneity of programmed death ligand 1 (PD-L1) expression causes discordance of PD-L1 expression between paired samples remains unclear. Here, PD-L1 status was,compared between whole sections from NSCLCs and the corresponding tissue microarrays (TMAs) serving as surrogate biopsy specimens.Methods: PD-L1 expression was evaluated by 22C3 immunohistochemistry assay on 190 archival surgical specimens and matched to the TMA results. PD-L1 expression was determined by the tumor proportion score (TPS) and classified as TPS lower than 1%, TPS of 1% to 49%, and TPS of 50% or higher. Agreement statistics were used.Results: The percentage of PD-L1 expression on tumor cells differed greatly between individual TMAs and matched surgical specimens. When PD-L1 TPS was adopted, a total of 36 of 190 discordance cases (18.9%) were observed, with a x-value of 0.630 between paired samples. The TMAs underestimated or overestimated PD-L1 status in 19 of 36 (52.8%) and 17 of 36 (47.2%) of the matched surgical specimens, respectively (p = 0.118). The discordance rate was much lower in cases with a PD-L1 TPS lower than 1% compared with in cases with a TPS of 1% to 49% and TPS of 50% or higher (18.4% versus 56.7% and 43.3%, p < 0.001). When a TPS of 50% or higher was used as the cutoff, the discordance rate of PD-L1 TPS less than 50% was further reduced to 7.5%. Such discrepancies were due mainly to intratumoral heterogeneity of PD-L1 expression and nonsignificant association with clinicopathological features.Conclusions: PD-L1 expression in TMAs correlates moderately well with that in the corresponding surgical specimens, indicating that evaluating PD-L1 expression in diagnostic biopsy specimens could be misleading in defining sensitivity to pembrolizumab treatment yet may be reliable as a way to exclude patients with a PD-L1 TPS less than 50% from first-line pembrolizumab treatment. (C) 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.