title: Development of a Prototype Immunohistochemistry Assay to Measure Programmed Death Ligand-1 Expression in Tumor Tissue.
abstract: BACKGROUND
  - With the abundance of therapeutics targeted against programmed death receptor-1 and its ligand (PD-L1) that are currently approved or in clinical development, there is interest in identifying those patients most likely to respond to these drugs. Expression of PD-L1 may be an indicator of an initial and robust inflammatory response to the presence of tumor cells. Therefore, tumors that express PD-L1 may be the most likely to respond to therapies that interrupt the negative feedback mechanism that leads to PD-L1 upregulation.
  
  
  OBJECTIVE
  - To develop a prototype immunohistochemistry assay using the anti-PD-L1 antibody clone 22C3.
  
  
  METHODS
  - The assay was developed and optimized using commercially available reagents and archival tumor-bank tissue.
  
  
  RESULTS
  - The optimized immunohistochemistry method had high precision and reproducibility. Using the prototype assay in 142 non-small cell lung cancer and 79 melanoma archival tumor-bank tissue samples, PD-L1 staining was observed at the plasma membrane of nucleated tumor and nontumor cells and, in some cases, as a distinct lichenoid pattern at the tumor-stroma border. Using a preliminary scoring method, 56% (80 of 142) of non-small cell lung cancer and 53% (42 of 79) of melanoma samples were defined as PD-L1+based on a modified H-score of 1 or more or the presence of a distinctive staining pattern at the tumor-stroma interface.
  
  
  CONCLUSIONS
  - The immunohistochemistry assay using the anti-PD-L1 antibody 22C3 merits further investigation in clinical trials and prevalence assessments to further understand the prognostic and predictive value of PD-L1 expression in cancer.
authors: From the Departments of Molecular Biomarkers and Diagnostics (Drs Dolled-Filhart, Pierce, Weiner, Wu, and Emancipator) and Profiling and Expression (Dr Yearley), Merck & Co, Inc, Kenilworth, New Jersey; the Departments of Early Clinical & Translational Research, Clinical Histochemistry (Dr Locke), Research and Clinical Client Services (Dr Murphy), and Operations and Client Services (Dr Lynch), QualTek Molecular Laboratories, Newtown, Pennsylvania; and the Department of Pathology, Eisenhower Medical Center, Rancho Mirage, California (Dr Frisman). Dr Locke is now with Bristol-Myers Squibb, Princeton, New Jersey; Dr Pierce is now with OncoSec Medical, Inc, San Diego, California; Dr Weiner is now with Daiichi Sankyo, Edison, New Jersey; and Dr Wu is currently at Janssen Research & Development, Spring House, Pennsylvania.
authors: Marisa
authors: M
authors: Dolled-Filhart
authors: Darren
authors: D
authors: Locke
authors: Tiffany
authors: T
authors: Murphy
authors: Frank
authors: F
authors: Lynch
authors: Jennifer H
authors: JH
authors: Yearley
authors: Dennis
authors: D
authors: Frisman
authors: Robert
authors: R
authors: Pierce
authors: Russell
authors: R
authors: Weiner
authors: Dianna
authors: D
authors: Wu
authors: Kenneth
authors: K
authors: Emancipator
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000918:Antibody Specificity; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016466:CHO Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells; D003412:Cricetulus; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014015:Tissue Banks
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D009363:Neoplasm Proteins; D011994:Recombinant Proteins