PD-L1 testing of non-small cell lung cancer using different antibodies and platforms: a Swiss cross-validation study

• Published in: Virchows Archiv : an international journal of pathology 2019-07, Vol.475 (1), p.67-76
• Main Authors: Savic, Spasenija, Berezowska, Sabina, Eppenberger-Castori, Serenella, Cathomas, Gieri, Diebold, Joachim, Fleischmann, Achim, Jochum, Wolfram, Komminoth, Paul, McKee, Thomas, Letovanec, Igor, Jasarevic, Zerina, Rössle, Matthias, Singer, Gad, von Gunten, Michael, Zettl, Andreas, Zweifel, Roland, Soltermann, Alex, Bubendorf, Lukas
• Format: Article
• Language: English
• Subjects: Antibodies; Antibodies - immunology; Assaying; Automation, Laboratory; B7-H1 Antigen - analysis; Biomarkers, Tumor - analysis; Carcinoma, Non-Small-Cell Lung - chemistry; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - pathology; Humans; Immunohistochemistry; Immunohistochemistry - instrumentation; Immunohistochemistry - methods; Immunohistochemistry - standards; Lung cancer; Lung Neoplasms - chemistry; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Medicine; Medicine & Public Health; Monoclonal antibodies; Non-small cell lung carcinoma; Observer Variation; Original Article; Pathology; PD-L1 protein; Pembrolizumab; Platforms; Predictive Value of Tests; Reproducibility of Results; Staining; Switzerland; Targeted cancer therapy; Tissue Array Analysis
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-019-02582-0

With the approval of pembrolizumab for first- and second-line treatment of PD-L1+ non-small cell lung cancer (NSCLC), PD-L1 testing by immunohistochemistry (IHC) has become a necessity. However, the DAKO autostainer ASL48 for the FDA approved DAKO 22C3 pharmDx assay is not broadly available in Switzerland and other parts of Europe. The primary goal of this study was to cross-validate the 22C3 anti-PD-L1 antibody on Benchmark Ultra (VBMU) and Leica Bond (LBO) immunostainers. IHC protocols were developed for 22C3 on both platforms with the 22C3phDx using ASL48 as reference. A tissue microarray (TMA) was constructed from 23 NSCLC specimens with a range of PD-L1 staining results. Empty TMA sections and the 22C3 antibody were distributed to 16 participants for staining on VBMU (8 centers) and/or LBO (12 centers) using the centrally developed protocols. Additionally the performance of the Ventana SP263 assay was tested in five centers. IHC scoring was performed centrally. Categorical PD-L1 staining (0–49% vs. 50–100%) did not significantly differ between centers using VBMU, whereas data from LBO were highly variable ( p