Ilié Marius, Ngo-Mai Mélanie, Long-Mira Elodie, Lassalle Sandra, Butori Catherine, Bence Coraline, Hamila Marame, Hofman Véronique, Hofman Paul
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Hospital University Federation OncoAge, Université Côte d'Azur; Institute for Research on Cancer and Aging in Nice (Inserm U1081 and CNRS 7284), Université Côte d'Azur; Hospital-Integrated Biobank (BB-0033-00025), Pasteur Hospital, Université Côte d'Azur;
Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Hospital University Federation OncoAge, Université Côte d'Azur.
J Vis Exp. 2018 Sep 25(139):58082. doi: 10.3791/58082.
Pembrolizumab monotherapy has been approved for the first- and second-line treatment of patients with PD-L1-expressing advanced non-small cell lung cancer (NSCLC). Testing for PD-L1 expression with the PD-L1 immunohistochemistry (IHC) 22C3 companion diagnostic assay, which gives a tumor proportion score (TPS), has been validated on tumor tissue. We developed an optimized laboratory-developed test (LDT) that uses the 22C3 antibody (Ab) concentrate on a widely available IHC autostainer for biopsy and cytology specimens. The PD-L1 TPS was evaluated with 120 paired whole-tumor tissue sections and biopsy samples and with 70 paired biopsy and cytology samples (bronchial washes, n = 40; pleural effusions, n = 30). The 22C3 Ab concentrate-based LDT showed a high concordance rate between biopsy (100%) and cytology (95%) specimens when compared to PD-L1 IHC expression determined using the PD-L1 IHC 22C3 companion assay at both TPS cut points (≥1%, ≥50%). The optimized LDT presented here, using the 22C3 Ab concentrate to determine the PD-L1 expression in both tumor tissue and in cytology specimens, will expand the ability of laboratories worldwide to assess the eligibility of patients with NSCLC for treatment with pembrolizumab monotherapy in a reliable and reproducible manner.
帕博利珠单抗单药疗法已被批准用于治疗表达PD-L1的晚期非小细胞肺癌（NSCLC）患者的一线和二线治疗。使用PD-L1免疫组织化学（IHC）22C3伴随诊断检测法检测PD-L1表达，该检测法可得出肿瘤比例评分（TPS），已在肿瘤组织上得到验证。我们开发了一种优化的实验室自建检测方法（LDT），该方法使用22C3抗体（Ab）浓缩液，通过广泛使用的免疫组织化学自动染色仪对活检和细胞学标本进行检测。对120对全肿瘤组织切片和活检样本以及70对活检和细胞学样本（支气管灌洗样本40例，胸腔积液样本30例）进行了PD-L1 TPS评估。在两个TPS切点（≥1%，≥50%）下，与使用PD-L1 IHC 22C3伴随检测法确定的PD-L1 IHC表达相比，基于22C3 Ab浓缩液的LDT在活检标本（100%）和细胞学标本（95%）之间显示出较高的一致性率。本文介绍的优化LDT，使用22C3 Ab浓缩液来确定肿瘤组织和细胞学标本中的PD-L1表达，将以可靠且可重复的方式扩展全球实验室评估NSCLC患者接受帕博利珠单抗单药治疗资格的能力。
