title: Relationship of tumor PD-L1 expression with EGFR wild-type status and poor prognosis in lung adenocarcinoma.
abstract: BACKGROUND
  Programmed death-ligand 1 is an immune modulator that promotes immunosuppression by binding to programmed death-1 of T-lymphocytes. Whereas programmed death-ligand 1 expression has been shown to be associated with the clinical response to anti-programmed death-ligand 1 antibody, the association of tumor programmed death-ligand 1 expression with clinicopathological/molecular features and with prognosis remains inconclusive in lung adenocarcinoma. We therefore examined the association of programmed death-ligand 1 expression with the clinicopathological/molecular features and prognosis of lung adenocarcinoma.
  
  
  METHODS
  Using tissue microarrays of 268 consecutive cases of lung adenocarcinoma, we evaluated programmed death-ligand 1 expression by immunohistochemistry. We examined the association of programmed death-ligand 1 expression with clinicopathological and molecular features. We also examined the prognostic association of programmed death-ligand 1 expression, using the log-rank test as well as Cox proportional hazards regression models to compute the mortality hazard ratio (HR).
  
  
  RESULTS
  Programmed death-ligand 1 immunoreactivity (at least 5% of the tumor cells) was observed in 43 (16%) of 268 cases of lung adenocarcinoma. Programmed death-ligand 1 positivity was associated with less tumor differentiation (P < 0.0001) and EGFR wild-type status (P = 0.0008). In a multivariable logistic regression analysis, less tumor differentiation was independently associated with programmed death-ligand 1 positivity (multivariable odds ratio, 6.54; 95% confidence interval [CI], 2.37-23.3; P = 0.0001). Programmed death-ligand 1 positivity was associated with a poor prognosis for lung cancer-specific survival (log-rank, P = 0.019; HR, 1.73; 95% CI, 1.06-2.72; P = 0.030) and overall survival (log-rank, P = 0.0014; HR, 1.88; 95% CI, 1.25-2.74).
  
  
  CONCLUSIONS
  Our study demonstrated that programmed death-ligand 1 positivity in lung adenocarcinoma was associated with less tumor differentiation and EGFR wild-type status, as well as a poor prognosis.
authors: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research , Tokyo.
authors: Kentaro
authors: K
authors: Inamura
authors: Translational Medicine & Clinical Pharmacology Department, Daiichi Sankyo Co., Ltd., Tokyo.
authors: Yusuke
authors: Y
authors: Yokouchi
authors: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research , Tokyo Department of Integrated Pulmonology, Tokyo Medical and Dental University, Tokyo.
authors: Rie
authors: R
authors: Sakakibara
authors: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research , Tokyo.
authors: Maki
authors: M
authors: Kobayashi
authors: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research , Tokyo.
authors: Sophia
authors: S
authors: Subat
authors: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research , Tokyo.
authors: Hironori
authors: H
authors: Ninomiya
authors: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research , Tokyo.
authors: Hiroko
authors: H
authors: Nagano
authors: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research , Tokyo.
authors: Kimie
authors: K
authors: Nomura
authors: Thoracic Oncology Center, The Cancer Institute Hospital, Japanese Foundation for Cancer Research , Tokyo, Japan.
authors: Sakae
authors: S
authors: Okumura
authors: Division of Pathology, The Cancer Institute; Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research , Tokyo ishikawa@jfcr.or.jp.
authors: Yuichi
authors: Y
authors: Ishikawa
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D040081:Protein Array Analysis
chemical_list: D060890:B7-H1 Antigen; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: PD-L1; driver mutation; immune checkpoint; lung cancer; outcome