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

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

Author information

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

PMID:
29800747
DOI:
10.1016/j.jtho.2018.05.013
[Indexed for MEDLINE]
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