title: Investigation of PD-L1 Biomarker Testing Methods for PD-1 Axis Inhibition in Non-squamous Non-small Cell Lung Cancer.
abstract: Inhibitors of the programmed cell death 1 (PD-1) signaling axis have recently demonstrated efficacy and are rapidly being incorporated into the treatment of non-small cell lung cancers (NSCLCs). Despite clear benefits to certain patients, the association of these responses with a predictive biomarker remains uncertain. Several different biomarkers have been proposed, with differing results and conclusions. This study compares multiple methods of biomarker testing for treatment of NSCLCs with PD1-axis inhibitors. Tissue microarrays of matched primary and metastatic NSCLCs were used to compare four different PD-1 ligand (PD-L1) IHC techniques, as well as RNA ISH. Additional cases with whole genome and transcriptome data were assessed for molecular correlates of PD-L1 overexpression. Eighty cases were included in the IHC study. Multiple IHC methodologies showed a high rate of agreement (Kappa = 0.67). When calibrated to RNA expression, agreement improved significantly (Kappa = 0.90, p=0.0049). PD-L1 status of primary and metastatic tumors was discordant in 17 (22%) cases. This study suggests that different IHC methodologies for PD-L1 assessment provide slightly different results. There is significant discordance between the PD-L1 status of primary tumors and lymph node metastases. RNA ISH may be a useful adjunct to complement PD-L1 IHC testing.
authors: Department of Pathology, Abbotsford Regional Hospital and Cancer Centre, British
  Columbia, Canada (BSS)
authors: Brandon S
authors: BS
authors: Sheffield
authors: PhenoPath Laboratories, Seattle, Washington (RF, CJ, AMG)
authors: Regan
authors: R
authors: Fulton
authors: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada (BSS, SEK, SZ, SY);
authors: Steve E
authors: SE
authors: Kalloger
authors: Trev and Joyce Deeley Research Centre BC Cancer ,Agency, Vancouver, British Columbia, Canada(KM, BHN)
authors: Katy
authors: K
authors: Milne
authors: BC Cancer Agency, Vancouver, British Columbia, CanadaDivision of Medical Oncology ,BC Cancer Agency, Vancouver, British Columbia, Canada(GG, JL, CH),
authors: Georgia
authors: G
authors: Geller
authors: BC Cancer Agency, Vancouver, British Columbia, CanadaCanada's Michael Smith Genome Sciences Centre ,BC Cancer Agency, Vancouver, British Columbia, Canada (MJ, EZ, EP, SJMJ, MAM)
authors: Martin
authors: M
authors: Jones
authors: PhenoPath Laboratories, Seattle, Washington (RF, CJ, AMG)
authors: Celine
authors: C
authors: Jacquemont
authors: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada (BSS, SEK, SZ, SY);
authors: Susanna
authors: S
authors: Zachara
authors: BC Cancer Agency, Vancouver, British Columbia, CanadaCanada's Michael Smith Genome Sciences Centre ,BC Cancer Agency, Vancouver, British Columbia, Canada (MJ, EZ, EP, SJMJ, MAM)
authors: Eric
authors: E
authors: Zhao
authors: BC Cancer Agency, Vancouver, British Columbia, CanadaCanada's Michael Smith Genome Sciences Centre ,BC Cancer Agency, Vancouver, British Columbia, Canada (MJ, EZ, EP, SJMJ, MAM)
authors: Erin
authors: E
authors: Pleasance
authors: BC Cancer Agency, Vancouver, British Columbia, CanadaDivision of Medical Oncology ,BC Cancer Agency, Vancouver, British Columbia, Canada(GG, JL, CH),
authors: Janessa
authors: J
authors: Laskin
authors: BC Cancer Agency, Vancouver, British Columbia, CanadaCanada's Michael Smith Genome Sciences Centre ,BC Cancer Agency, Vancouver, British Columbia, Canada (MJ, EZ, EP, SJMJ, MAM)
authors: Steven J M
authors: SJ
authors: Jones
authors: BC Cancer Agency, Vancouver, British Columbia, CanadaCanada's Michael Smith Genome Sciences Centre ,BC Cancer Agency, Vancouver, British Columbia, Canada (MJ, EZ, EP, SJMJ, MAM)
authors: Marco A
authors: MA
authors: Marra
authors: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada (BSS, SEK, SZ, SY);
authors: Stephen
authors: S
authors: Yip
authors: Trev and Joyce Deeley Research Centre BC Cancer ,Agency, Vancouver, British Columbia, Canada(KM, BHN)
authors: Brad H
authors: BH
authors: Nelson
authors: PhenoPath Laboratories, Seattle, Washington (RF, CJ, AMG)
authors: Allen M
authors: AM
authors: Gown
authors: BC Cancer Agency, Vancouver, British Columbia, CanadaDivision of Medical Oncology ,BC Cancer Agency, Vancouver, British Columbia, Canada(GG, JL, CH),
authors: Cheryl
authors: C
authors: Ho
authors: Department of Laboratory Medicine and Pathology , BC Cancer Agency, Vancouver, British Columbia, Canada(DNI)
authors: Diana N
authors: DN
authors: Ionescu
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D002138:Calibration; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000592:standards; D008175:Lung Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D012313:RNA / Q000032:analysis; D012189:Retrospective Studies
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012313:RNA
keywords: NSCLC; PD-1; PD-L1; biomarker; immunotherapy; lung cancer; non–small cell lung carcinoma