Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, New Territories, Hong Kong.
State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, New Territories, Hong Kong.
Mod Pathol. 2018 Sep;31(9):1381-1390. doi: 10.1038/s41379-018-0053-3. Epub 2018 Apr 30.
Immune checkpoint blockade targeting the PD-1/PD-L1 axis has recently demonstrated efficacy and promise in cancer treatment. Appropriate biomarker selection is therefore essential for improving treatment efficacy. However, the establishment of PD-L1 assay in pathology laboratories is complicated by the presence of multiple testing platforms using different scoring systems. Here we assessed the PD-L1 expression in 713 consecutive non-small cell lung carcinomas by four commercially available PD-L1 immunohistochemical assays, namely, 22C3, 28-8, SP142 and SP263. The analytical performances of the four assays and diagnostic performances across clinically relevant cutoffs were evaluated. The prevalence of PD-L1 (22C3) expression was 21% with a ≥50% cutoff and 56% with a ≥1% cutoff. High PD-L1 expression (using a ≥50% cutoff) was significantly associated with male sex (P = 0.001), ever smoking history (P < 0.001), squamous cell carcinoma (P = 0.001), large cell carcinoma (P < 0.001), lymphoepithelioma-like carcinoma (P = 0.006), sarcomatoid carcinoma (P < 0.001), mutant KRAS (P = 0.005) and wild-type EGFR (P = 0.003). Elevated PD-L1 expression was also significantly associated with shorter survival in patients with adenocarcinoma (log-rank P = 0.026) and remained an independent prognostic factor by multivariable analysis. Among the four assays, 22C3, 28-8 and SP263 were highly concordant for tumor cell scoring. With a cutoff of ≥50% (i.e., the threshold for first-line patient selection), inter-rater agreement was high among the three assays with percentage agreement >97%. In conclusion, three PD-L1 assays showed good analytical performance and a high agreement with each other, but not all cases were correctly classified using the same clinical cutoff. Further studies comparing the predictive value of these assays are required to address the interchangeability of these assays for clinical use.
免疫检查点阻断针对 PD-1/PD-L1 轴在癌症治疗中最近显示出疗效和前景。因此，适当的生物标志物选择对于提高治疗效果至关重要。然而，由于存在使用不同评分系统的多种检测平台，病理实验室中 PD-L1 检测的建立较为复杂。在这里，我们通过四种市售的 PD-L1 免疫组化检测（22C3、28-8、SP142 和 SP263）评估了 713 例连续的非小细胞肺癌中的 PD-L1 表达。评估了四种检测方法的分析性能和临床相关截止值下的诊断性能。PD-L1（22C3）表达的患病率为 21%，截断值为≥50%；56%，截断值为≥1%。高 PD-L1 表达（使用≥50%截断值）与男性（P=0.001）、吸烟史（P<0.001）、鳞状细胞癌（P=0.001）、大细胞癌（P<0.001）、淋巴上皮样癌（P=0.006）、肉瘤样癌（P<0.001）、突变型 KRAS（P=0.005）和野生型 EGFR（P=0.003）显著相关。在腺癌患者中，高 PD-L1 表达与生存时间缩短显著相关（对数秩检验 P=0.026），且多变量分析仍为独立预后因素。在四种检测中，22C3、28-8 和 SP263 对肿瘤细胞评分高度一致。使用≥50%（即一线患者选择的阈值）的截止值，三种检测之间的观察者间一致性较高，百分比一致性>97%。总之，三种 PD-L1 检测均表现出良好的分析性能，彼此之间具有高度一致性，但并非所有病例均使用相同的临床截止值进行正确分类。需要进一步研究这些检测的预测价值，以解决这些检测在临床应用中的可互换性。
