title: PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project.
abstract: The Blueprint Programmed Death Ligand 1 (PD-L1) Immunohistochemistry (IHC) Assay Comparison Project is an industrial-academic collaborative partnership to provide information on the analytical and clinical comparability of four PD-L1 IHC assays used in clinical trials.
  
  
  
  A total of 39 NSCLC tumors were stained with four PD-L1 IHC assays (22C3, 28-8, SP142, and SP263), as used in the clinical trials. Three experts in interpreting their respective assays independently evaluated the percentages of tumor and immune cells staining positive at any intensity. Clinical diagnostic performance was assessed through comparisons of patient classification above and below a selected expression cutoff and by agreement using various combinations of assays and cutoffs.
  
  
  
  Analytical comparison demonstrated that the percentage of PD-L1-stained tumor cells was comparable when the 22C3, 28-8, and SP263 assays were used, whereas the SP142 assay exhibited fewer stained tumor cells overall. The variability of immune cell staining across the four assays appears to be higher than for tumor cell staining. Of the 38 cases, 19 (50.0%) were classified above and five (13%) were classified below the selected cutoffs of all assays. For 14 of the 38 cases (37%), a different PD-L1 classification would be made depending on which assay/scoring system was used.
  
  
  
  The Blueprint PD-L1 IHC Assay Comparison Project revealed that three of the four assays were closely aligned on tumor cell staining whereas the fourth showed consistently fewer tumor cells stained. All of the assays demonstrated immune cell staining, but with greater variability than with tumor cell staining. By comparing assays and cutoffs, the study indicated that despite similar analytical performance of PD-L1 expression for three assays, interchanging assays and cutoffs would lead to "misclassification" of PD-L1 status for some patients. More data are required to inform on the use of alternative staining assays upon which to read different specific therapy-related PD-L1 cutoffs.
authors.affiliation: Medicine and Pathology, University of Colorado Cancer Center, Aurora, Colorado; International Association for the Study of Lung Cancer, Aurora, Colorado. Electronic address: Fred.Hirsch@ucdenver.edu.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
authors.affiliation: Personal Genome Diagnostics, Baltimore, Maryland.
authors.forename: Abigail
authors.initials: A
authors.lastname: McElhinny
authors.affiliation: Dako North America, Agilent Technologies, Carpinteria, California.
authors.forename: Dave
authors.initials: D
authors.lastname: Stanforth
authors.affiliation: Ventana Medical Systems, Inc., Roche Tissue Diagnostics, Tucson, Arizona.
authors.forename: James
authors.initials: J
authors.lastname: Ranger-Moore
authors.affiliation: Dako North America, Agilent Technologies, Carpinteria, California.
authors.forename: Malinka
authors.initials: M
authors.lastname: Jansson
authors.affiliation: Dako North America, Agilent Technologies, Carpinteria, California.
authors.forename: Karina
authors.initials: K
authors.lastname: Kulangara
authors.affiliation: Ventana Medical Systems, Inc., Roche Tissue Diagnostics, Tucson, Arizona.
authors.forename: William
authors.initials: W
authors.lastname: Richardson
authors.affiliation: Ventana Medical Systems, Inc., Roche Tissue Diagnostics, Tucson, Arizona.
authors.forename: Penny
authors.initials: P
authors.lastname: Towne
authors.affiliation: Dako North America, Agilent Technologies, Carpinteria, California.
authors.forename: Debra
authors.initials: D
authors.lastname: Hanks
authors.affiliation: Ventana Medical Systems, Inc., Roche Tissue Diagnostics, Tucson, Arizona.
authors.forename: Bharathi
authors.initials: B
authors.lastname: Vennapusa
authors.affiliation: Ventana Medical Systems, Inc., Roche Tissue Diagnostics, Tucson, Arizona.
authors.forename: Amita
authors.initials: A
authors.lastname: Mistry
authors.affiliation: American Association for Cancer Research, Washington, DC; Genentech, Washington, DC.
authors.forename: Rasika
authors.initials: R
authors.lastname: Kalamegham
authors.affiliation: Development, Oncology and Pharmacodiagnostics, Bristol-Myers Squibb Company, Princeton, New Jersey.
authors.forename: Steve
authors.initials: S
authors.lastname: Averbuch
authors.affiliation: Development, Oncology and Pharmacodiagnostics, Bristol-Myers Squibb Company, Princeton, New Jersey.
authors.forename: James
authors.initials: J
authors.lastname: Novotny
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey.
authors.forename: Eric
authors.initials: E
authors.lastname: Rubin
authors.affiliation: Merck & Co., Inc., Kenilworth, New Jersey.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Emancipator
authors.affiliation: Genentech, Oncology Biomarkers Development, South San Francisco, California; Corvus Pharmaceuticals, Burlingame, California.
authors.forename: Ian
authors.initials: I
authors.lastname: McCaffery
authors.affiliation: Genentech, Oncology Biomarkers Development, South San Francisco, California.
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Williams
authors.affiliation: AstraZeneca, Cambridge, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Walker
authors.affiliation: Carolinas Pathology Group, Carolinas HealthCare System, Charlotte, North Carolina.
authors.forename: John
authors.initials: J
authors.lastname: Longshore
authors.affiliation: Department of Pathology, University Health Network, Princess Margaret Cancer Centre and University of Toronto, Ontario, Canada.
authors.forename: Ming Sound
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: Department of Pathology, Aberdeen University Medical School and Aberdeen Royal Infirmary, Aberdeen, Scotland.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Kerr
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D001681:Biological Assay / Q000379:methods*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor
keywords: Immunohistochemistry; Immunotherapy; Lung cancer; PD-L1 assays