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 Russell; Jennifer Sauter; Erik Thunnissen; Ignacio Wistuba; Hui Yu; Murry W Wynes; Melania Pintilie; Yasushi Yatabe; Fred R Hirsch

doi:10.1016/j.jtho.2018.05.013

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

J Thorac Oncol. 2018 Sep;13(9):1302-1311. doi: 10.1016/j.jtho.2018.05.013. Epub 2018 May 22.

Authors

Ming Sound Tsao¹, Keith M Kerr², Mark Kockx³, Mary-Beth Beasley⁴, Alain C Borczuk⁵, Johan Botling⁶, Lukas Bubendorf⁷, Lucian Chirieac⁸, Gang Chen⁹, Teh-Ying Chou¹⁰, Jin-Haeng Chung¹¹, Sanja Dacic¹², Sylvie Lantuejoul¹³, Mari Mino-Kenudson¹⁴, Andre L Moreira¹⁵, Andrew G Nicholson¹⁶, Masayuki Noguchi¹⁷, Giuseppe Pelosi¹⁸, Claudia Poleri¹⁹, Prudence A Russell²⁰, Jennifer Sauter²¹, Erik Thunnissen²², Ignacio Wistuba²³, Hui Yu²⁴, Murry W Wynes²⁵, Melania Pintilie²⁶, Yasushi Yatabe²⁷, Fred R Hirsch²⁸

Affiliations

¹ Department of Pathology, University Health Network/Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
² Department of Pathology, Aberdeen Royal Infirmary, Aberdeen University Medical School, Aberdeen, Scotland, United Kingdom.
³ HistoGeneX, Antwerp, Belgium.
⁴ Department of Pathology, Mount Sinai Medical Center, New York, New York.
⁵ Department of Pathology, Weill Cornell Medicine, New York, New York.
⁶ Department of Immunology Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
⁷ Institute of Pathology, University Hospital Basel, Pathologie, Basel, Switzerland.
⁸ Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
⁹ Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
¹⁰ Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Republic of China.
¹¹ Department of Pathology and Respiratory Center, Seoul National University Bundang Hospital, Seongnam city, Gyeonggi-do, Republic of Korea.
¹² Department of Pathology University of Pittsburgh, Pittsburgh, Pennsylvania.
¹³ Department of Biopathology, Centre Léon Bérard, Lyon, France.
¹⁴ Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
¹⁵ New York University Langone Health, Department of Pathology, New York, New York.
¹⁶ Department of Histopathology, Royal Brompton and Harefield National Health Service Foundation Trust and National Heart and Lung Institute, Imperial College, London, United Kingdom.
¹⁷ Department of Pathology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
¹⁸ Department of Oncology and Hemato-Oncology, University of Milan, and Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Gruppo, MultiMedica, Milan, Italy.
¹⁹ Office of Pathology Consultants, Buenos Aires, Argentina.
²⁰ St, Vincent's Pathology, Fitzroy, Victoria, Australia.
²¹ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
²² Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands.
²³ Department of Translational Molecular Pathology, M. D. Anderson Cancer Center, Houston, Texas.
²⁴ University of Colorado Anschutz Medical Campus, Aurora, Colorado.
²⁵ International Association for the Study of Lung Cancer, Aurora, Colorado.
²⁶ Department of Biostatistics, University Health Network, Princess Margaret Cancer Centre Toronto, Ontario, Canada.
²⁷ Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.
²⁸ University of Colorado Anschutz Medical Campus, Aurora, Colorado; International Association for the Study of Lung Cancer, Aurora, Colorado. Electronic address: Fred.Hirsch@ucdenver.edu.

Abstract

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.

Keywords: Checkpoint inhibitors; Companion diagnostics; Complementary diagnostics; Cytology; Immunooncology; Pathology.

Publication types

Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

B7-H1 Antigen / immunology*
Humans
Immunohistochemistry / methods*

Substances

B7-H1 Antigen
CD274 protein, human

Grants and funding

P30 CA008748/CA/NCI NIH HHS/United States