Objectives

Multiple programmed cell death ligand-1 (PD-L1) immunohistochemistry assays are currently used as companion or complementary diagnostic tools for anti-programmed cell death-1 immunotherapies. We aimed to characterize two PD-L1 immunohistochemistry assays (Dako 22C3 and 28-8) for non-small cell lung cancer (NSCLC) in clinical laboratories.

Materials and methods

Surgical specimens from 420 patients with pathological stages IA to IIIA NSCLC were investigated. The archived samples were freshly cut into 5-μm-thick sections stained with antibodies 22C3 and 28-8, and tumoral PD-L1 expression was evaluated in two clinical laboratories, respectively. Overall, positive, and negative percent agreement (OPA, PPA, and NPA, respectively) at specified PD-L1 cutoffs were calculated to assess the concordance between 22C3 and 28-8 assays.

Results

Tumoral PD-L1 expression of ≥ 1% was detected by either 22C3 or 28-8 assays in 176 cases (41.9%), whereas 22C3 revealed a significantly higher tumoral PD-L1 expression compared to 28-8 (median 30% vs. 10%, p < 0.0001). OPA was 89.0, 90.2, and 91.9% at 1, 25, and 50% cutoff levels. When 22C3 was compared to a standard assay 28-8, the PPA was 85.5, 98.3, and 94.9%, whereas NPA was 91.0, 89.0, and 91.6% at 1, 25, and 50%. On the other hand, when 28-8 was compared to 22C3, PPA was 84.4% at 1%, but it decreased to 58.3 and 53.6% at 25 and 50%; whereas NPA remained high (91.7, 99.7, and 99.4% at 1, 25 and 50%, respectively).

Conclusion

Our analysis revealed that, despite the high OPA, there was discordance in the PPA between 22C3 as a standard assay and 28-8 as a comparator assay at 25% and 50% PD-L1 cutoff levels, indicating that the results of 28-8 could be translated to those of 22C3 but not vice versa.

中文翻译：

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使用22C3和28-8抗体治疗非小细胞肺癌的程序性细胞死亡配体1免疫组织化学分析的比较研究：420例来自日本患者的手术标本的分析

目标

目前，多种程序性细胞死亡配体1（PD-L1）免疫组织化学测定已用作抗程序性细胞死亡1免疫疗法的辅助或补充诊断工具。我们旨在表征临床实验室中针对非小细胞肺癌（NSCLC）的两种PD-L1免疫组织化学测定法（Dako 22C3和28-8）。

材料和方法

研究人员对420例IA至IIIA期NSCLC病理分期患者的手术标本进行了研究。将存档的样品新鲜切成5μm厚的切片，用抗体22C3和28-8染色，并分别在两个临床实验室中评估肿瘤PD-L1的表达。计算特定PD-L1临界值时的总体，阳性和阴性百分比一致性（分别为OPA，PPA和NPA），以评估22C3和28-8分析之间的一致性。

结果

通过176例（41.9％）的22C3或28-8分析检测到的肿瘤PD-L1表达≥1％，而22C3显示与28-8相比肿瘤PD-L1表达显着更高（中位数30％比10 ％，p ＜0.0001）。截止值为1、25和50％时，OPA分别为89.0、90.2和91.9％。当将22C3与标准测定法28-8进行比较时，PPA分别为85.5、98.3和94.9％，而NPA在1、25和50％时分别为91.0、89.0和91.6％。另一方面，当将28-8与22C3进行比较时，PPA为1％时为84.4％，但在25％和50％时分别为58.3和53.6％；而NPA仍然很高（分别为1％，25％和50％，分别为91.7％，99.7和99.4％）。

结论

我们的分析显示，尽管OPA较高，但在25％和50％PD-L1截止水平下，PPA在22C3作为标准测定与28-8作为比较测定之间存在不一致，表明28-8的结果可以翻译成22C3的译本，反之亦然。