title: PD-L1 Expression by Two Complementary Diagnostic Assays and mRNA In Situ Hybridization in Small Cell Lung Cancer.
abstract: Therapeutic antibodies to immune checkpoints show promising results. Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand, blocks the cancer immunity cycle by binding the PD-L1 receptor (programmed death 1). We investigated PD-L1 protein expression and messenger RNA (mRNA) levels in SCLC.
  
  
  
  PD-L1 protein expression and mRNA levels were determined by immunohistochemistry (IHC) with SP142 and Dako 28-8 PD-L1 antibodies and in situ hybridization in primary tumor tissue microarrays in both tumor cells and tumor-infiltrating immune cells (TIICs) obtained from a limited-disease SCLC cohort of 98 patients. An additional cohort of 96 tumor specimens from patients with extensive-disease SCLC was assessed for PD-L1 protein expression in tumor cells with Dako 28-8 antibody only.
  
  
  
  The overall prevalence of PD-L1 protein expression in tumor cells was 16.5%. In the limited-disease cohort, the prevalences of PD-L1 protein expression in tumor cells with SP142 and Dako 28-8 were 14.7% and 19.4% (tumor proportion score cutoff ≥1%) and PD-L1 mRNA ISH expression was positive in 15.5% of tumor samples. Increased PD-L1 protein/mRNA expression was associated with the presence of more TIICs (p < 0.05). The extensive-disease cohort demonstrated a 14.9% positivity of PD-L1 protein expression in tumor cells with Dako 28-8 antibody.
  
  
  
  A subset of SCLCs is characterized by positive PD-L1 and/or mRNA expression in tumor cells. Higher PD-L1 and mRNA expression correlate with more infiltration of TIICs. The prevalence of PD-L1 in SCLC is lower than that published for NSCLC. The predictive role of PD-L1 expression in SCLC treatment remains to be established.
authors.affiliation: Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Hui
authors.initials: H
authors.lastname: Yu
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Cory
authors.initials: C
authors.lastname: Batenchuk
authors.affiliation: Radiation Oncology Center NU-Med, Elblag, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Badzio
authors.affiliation: Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Pathology, Moffitt Cancer Center, Tampa, Florida.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Boyle
authors.affiliation: Department of Pathomorphology, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Czapiewski
authors.affiliation: Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Chan
authors.affiliation: Department of Biostatisitics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Xian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biostatisitics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Gao
authors.affiliation: Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Kim
authors.initials: K
authors.lastname: Ellison
authors.affiliation: Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Kowalewski
authors.affiliation: Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Rivard
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Rafal
authors.initials: R
authors.lastname: Dziadziuszko
authors.affiliation: Department of Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Institute, Shanghai, People's Republic of China.
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Florida Cancer Specialists and Research Institute, Ocala, Florida.
authors.forename: Maen
authors.initials: M
authors.lastname: Hussein
authors.affiliation: Texas Oncology, Tyler, Texas.
authors.forename: Donald
authors.initials: D
authors.lastname: Richards
authors.affiliation: Cancer Care Centers of South Texas, San Antonio, Texas.
authors.forename: Sharon
authors.initials: S
authors.lastname: Wilks
authors.affiliation: Clopton Clinic, Jonesboro, Arkansas.
authors.forename: Marc
authors.initials: M
authors.lastname: Monte
authors.affiliation: Institute for Translational Oncology Research of Greenville Health System, Greenville, South Carolina.
authors.forename: William
authors.initials: W
authors.lastname: Edenfield
authors.affiliation: Blue Ridge Cancer Care, Blacksburg, Virginia.
authors.forename: Jerome
authors.initials: J
authors.lastname: Goldschmidt
authors.affiliation: The Center for Cancer and Blood Disorders, Fort Worth, Texas.
authors.forename: Ray
authors.initials: R
authors.lastname: Page
authors.affiliation: Texas Oncology-Wichita Falls, Texoma Cancer Center, Wichita Falls, Texas.
authors.forename: Brian
authors.initials: B
authors.lastname: Ulrich
authors.affiliation: Oncology Hematology Care, Cincinnati, Ohio.
authors.forename: David
authors.initials: D
authors.lastname: Waterhouse
authors.affiliation: Biostats Solutions, Frederick, Maryland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Close
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.affiliation: Bristol-Myers Squibb, Princeton, New Jersey.
authors.forename: Kimary
authors.initials: K
authors.lastname: Kulig
authors.affiliation: Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Electronic address: Fred.Hirsch@ucdenver.edu.
authors.forename: Fred R
authors.initials: FR
authors.lastname: Hirsch
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization / Q000379:methods*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics*; D012189:Retrospective Studies; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: IHC; PD-L1; SCLC; mRNA in situ hybridization