多中心协同研究：用于非小细胞肺癌的 PD-L1 IHC 检测
Multicenter harmonization study for PD-L1 IHC testing in non-small-cell lung cancer.
机构信息
Groupe PATTERN, Fondation Synergie Lyon Cancer, Lyon, France; Department of Biology and Pathology, Gustave Roussy, Villejuif, France.
Department of Biopathology, Centre Léon Bérard, Lyon, France.
出版信息
Ann Oncol. 2018 Apr 1;29(4):953-958. doi: 10.1093/annonc/mdy014.
BACKGROUND
Various programed death ligand 1 (PD-L1) immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small-cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDTs).
METHODS
IHC with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark Ultra (2 centers) platforms. For each matching platform, 22C3, 28-8 and SP263 assays were performed. For nonmatching platforms and other antibodies, LDTs were developed in each center. A total of 35 stainings were performed for each case across different platforms and antibodies. PD-L1 staining was assessed in tumor cells and immune cells by seven trained thoracic pathologists. For statistical analysis, 1%, 50% and 1%, 5%, 10% expression thresholds were used for tumor cells and immune cells, respectively.
RESULTS
28-8, 22C3 and SP263 assays were highly concordant for tumor cells staining across the five Dako or Ventana platforms. Among 27 LDTs developed in 7 centers on Dako, Ventana and Leica platforms, 14 (51.8%) demonstrated similar concordance when compared with reference assays for tumor cell staining. Clone SP263 achieved the highest concordance rate across all platforms. Lower concordance was observed for immune cells staining when using a four categories scale.
CONCLUSION
28-8, 22C3 and SP263 assays had close analytical performance for tumor cell staining across seven centers. Some LDTs on Dako, Ventana and Leica platforms achieved similar concordance, but caution is warranted for their validation. These LDTs will be further validated in order to provide recommendations for the use of assays and LDT for PD-L1 testing in NSCLC.
背景
为了使非小细胞肺癌（NSCLC）中的程序性死亡配体 1（PD-L1）检测标准化并广泛应用，我们开展了一项多中心研究，比较了 PD-L1 标准化检测方法和实验室开发的检测方法（LDT）。
方法
在 7 家中心的 41 例 NSCLC 手术标本上，使用 Dako Autostainer Link 48（3 家中心）、Leica Bond（2 家中心）或 Ventana BenchMark Ultra（2 家中心）平台，同时进行了五种抗 PD-L1 单克隆抗体（28-8、22C3、E1L3N、SP142 和 SP263）的免疫组化检测。对于每个匹配平台，我们进行了 22C3、28-8 和 SP263 检测。对于非匹配平台和其他抗体，在每个中心开发了 LDT。对于每个病例，我们在不同的平台和抗体上共进行了 35 次染色。7 位胸部病理学家对肿瘤细胞和免疫细胞的 PD-L1 染色进行了评估。对于统计分析，我们分别使用肿瘤细胞和免疫细胞的 1%、50%和 1%、5%、10%表达阈值。
结果
在五个 Dako 或 Ventana 平台上，28-8、22C3 和 SP263 检测方法在肿瘤细胞染色方面具有高度一致性。在 7 家中心开发的 27 种 Dako、Ventana 和 Leica 平台上的 LDT 中，14 种（51.8%）在肿瘤细胞染色方面与参考检测方法具有相似的一致性。克隆 SP263 在所有平台上的一致性率最高。当使用四级分类法时，免疫细胞染色的一致性较低。
结论
在七个中心，28-8、22C3 和 SP263 检测方法在肿瘤细胞染色方面具有密切的分析性能。Dako、Ventana 和 Leica 平台上的一些 LDT 具有相似的一致性，但需要对其进行验证。这些 LDT 将进一步验证，以便为 NSCLC 中 PD-L1 检测的检测方法和 LDT 的使用提供建议。
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