title: Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer.
abstract: BACKGROUND
  Recent clinical trials have shown that immune-checkpoint blockade yields a clinical response in a subset of individuals with advanced nonsmall-cell lung cancer (NSCLC). We examined whether the expression of programmed death-ligand 1 (PD-L1) is related to clinicopathologic or prognostic factors in patients with surgically resected NSCLC.
  
  
  METHODS
  The expression of PD-L1 was evaluated by immunohistochemical analysis in 164 specimens of surgically resected NSCLC. Cell surface expression of PD-L1 in NSCLC cell lines was quantified by flow cytometry.
  
  
  RESULTS
  Expression of PD-L1 in tumor specimens was significantly higher for women than for men, for never smokers than for smokers, and for patients with adenocarcinoma than for those with squamous cell carcinoma. Multivariate analysis revealed that the presence of epidermal growth factor receptor gene (EGFR) mutations and adenocarcinoma histology were significantly associated with increased PD-L1 expression in a manner independent of other factors. Cell surface expression of PD-L1 was also significantly higher in NSCLC cell lines positive for activating EGFR mutations than in those with wild-type EGFR. The EGFR inhibitor erlotinib downregulated PD-L1 expression in the former cell lines but not in the latter, suggesting that PD-L1 expression is increased by EGFR signaling conferred by activating EGFR mutations. A high level of PD-L1 expression in resected tumor tissue was associated with a significantly shorter overall survival for NSCLC patients.
  
  
  CONCLUSIONS
  High expression of PD-L1 was associated with the presence of EGFR mutations in surgically resected NSCLC and was an independent negative prognostic factor for this disease.
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume.
authors.forename: K
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors.forename: K
authors.initials: K
authors.lastname: Ota
authors.affiliation: Department of Diagnostic Pathology, Kurume University Hospital, Kurume.
authors.forename: A
authors.initials: A
authors.lastname: Kawahara
authors.affiliation: Biostatistics Center, Kurume University, Kurume.
authors.forename: S
authors.initials: S
authors.lastname: Hattori
authors.affiliation: Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors.forename: E
authors.initials: E
authors.lastname: Iwama
authors.affiliation: Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors.forename: T
authors.initials: T
authors.lastname: Harada
authors.affiliation: Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
authors.forename: K
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Surgery, Kurume University School of Medicine, Kurume.
authors.forename: S
authors.initials: S
authors.lastname: Takamori
authors.affiliation: Department of Diagnostic Pathology, Kurume University Hospital, Kurume.
authors.forename: M
authors.initials: M
authors.lastname: Kage
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume.
authors.forename: T
authors.initials: T
authors.lastname: Hoshino
authors.affiliation: Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Center for Clinical and Translational Research, Kyushu University Hospital, Fukuoka, Japan. Electronic address: okamotoi@kokyu.med.kyushu-u.ac.jp.
authors.forename: I
authors.initials: I
authors.lastname: Okamoto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR-TKI; PD-L1; activating EGFR mutation; immunohistochemistry; nonsmall-cell lung cancer