PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project

Ming Sound Tsao, Keith M. Kerr, Mark Kockx, Mary-Beth Beasley, Alain C. Borczuk, Johan Botling, Lukas Bubendorf, Lucian Chirieac, Gang Chen, Teh-Ying Chou, Jin-Haeng Chung, Sanja Dacic, Sylvie Lantuejoul, Mari Mino-Kenudson, Andre L. Moreira, Andrew G. Nicholson, Masayuki Noguchi, Giuseppe Pelosi, Claudia Poleri, Prudence A. RussellJennifer Sauter, Erik Thunnissen, Ignacio Wistuba, Hui Yu, Murry W. Wynes, Melania Pintilie, Yasushi Yatabe, Fred R. Hirsch

Research output: Contribution to journalArticleAcademicpeer-review


Objectives: The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples. Methods: BP2 were conducted using 81 lung cancer specimens of various histological and sample types, stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10); the slides were evaluated by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by using digital images, and samples prepared for cytological examination. PD-L1 expression was assessed for percentage (tumor proportional score) of tumor cell (TC) and immune cell areas showing PD-L1 staining, with TCs scored continuously or categorically with the cutoffs used in checkpoint inhibitor trials. Results: The BP2 results showed highly comparable staining by the 22C3, 28-8 and SP263 assays; less sensitivity with the SP142 assay; and higher sensitivity with the 73-10 assay to detect PD-L1 expression on TCs. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient [ICC] = 0.86–0.93), poor reliability in IC PD-L1 scoring (overall ICC = 0.18–0.19), and good agreement in assessing PD-L1 status on cytological cell block materials (ICC = 0.78–0.85). Conclusion: BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.
Original languageEnglish
Pages (from-to)1302-1311
JournalJournal of Thoracic Oncology
Issue number9
Publication statusPublished - 2018

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