title: PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma.
abstract: OBJECTIVE
  Immune checkpoint blockade using inhibitors of programmed death-1 have shown promise in early phase clinical trials in NSCLC and programmed death-ligand 1 (PD-L1) tumoral expression could potentially be a useful predictive marker. Data reporting the prevalence of PD-L1 expression in NSCLC and clinicopathologic associations is very limited. We sought to determine the frequency of PD-L1 expression in NSCLC and investigate associations with clinicopathologic features and patient outcome.
  
  
  METHODS
  PD-L1 expression was analyzed using immunohistochemistry (Merck; clone 22C3) in 678 stages I-III NSCLC and 52 paired nodal metastases using tissue microarrays. Tumors with ≥50% cells showing positive membrane staining were considered to have high expression of PD-L1.
  
  
  RESULTS
  PD-L1 expression of any intensity was identified in 32.8% of cases. High PD-L1 expression was found in 7.4% of NSCLC. Squamous cell carcinomas (8.1%) and large cell carcinomas (12.1%) showed high PD-L1 expression more commonly than adenocarcinomas (5.1%) but this was not statistically significant (p=0.072). High PD-L1 expression was associated with younger patient age and high tumor grade (p<0.05). There was no association with gender, tumor size, stage, nodal status, EGFR or KRAS mutation status. In multivariate analysis, patients with high PD-L1 expression had significantly longer overall survival (p<0.05).
  
  
  CONCLUSIONS
  PD-L1 is expressed at high levels in a significant proportion of NSCLC and appears to be a favorable prognostic factor in early stage disease. As there are potential sampling limitations using tissue microarrays to assess heterogeneously expressed biomarkers, and as the results may differ in advanced stage disease, further studies are recommended.
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; School of Medicine, The University of Western Sydney, Sydney, NSW, Australia. Electronic address: wendy.cooper@sswahs.nsw.gov.au.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Cooper
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Thang
authors.initials: T
authors.lastname: Tran
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia.
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Vilain
authors.affiliation: Melanoma Institute Australia, Sydney, NSW, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Madore
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Selinger
authors.affiliation: School of Medicine, The University of Western Sydney, Sydney, NSW, Australia; Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, NSW, Australia; UNSW Medicine, UNSW Australia, Sydney, NSW, Australia.
authors.forename: Maija
authors.initials: M
authors.lastname: Kohonen-Corish
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia; Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, NSW, Australia; Macarthur Cancer Therapy Centre, Campbelltown Hospital, Sydney, NSW, Australia.
authors.forename: PoYee
authors.initials: P
authors.lastname: Yip
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Medical Genomics, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Kinghorn Cancer Centre and Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: O'Toole
authors.affiliation: Sydney Cardiothoracic Surgeons, Royal Prince Alfred Medical Centre, Sydney, NSW, Australia.
authors.forename: Brian C
authors.initials: BC
authors.lastname: McCaughan
authors.affiliation: Merck & Co. Inc., Whitehouse Station, NJ, USA.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Yearley
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Horvath
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Kao
authors.affiliation: Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, Sydney, NSW, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Boyer
authors.affiliation: Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, University of Sydney, Sydney, NSW, Australia; Melanoma Institute Australia, Sydney, NSW, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Biomarker; Immunohistochemistry; Immunotherapy; Lung cancer; NSCLC; Programmed death-ligand 1