title: Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  To investigate the expression and prognostic role of programmed death ligand-1 (PD-L1) in locally advanced esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  A total of 200 patients with ESCC who underwent radical esophagectomy with standard lymphadenectomy as the initial definitive treatment in Seoul National University Hospital from December 2000 to April 2013 were eligible for this analysis. Tissue microarrays were constructed by collecting tissue cores from surgical specimens, and immunostained with antibodies directed against PD-L1, p16, and c-Met. Medical records were reviewed retrospectively to assess clinical outcomes. Patients were divided into two groups by PD-L1 status, and significant differences in clinicopathologic characteristics between the two groups were assessed.
  
  
  RESULTS
  Tumor tissues from 67 ESCC patients (33.5%) were PD-L1-positive. Positive p16 expression was observed in 21 specimens (10.5%). The H-score for c-Met expression was ≥ 50 in 42 specimens (21.0%). Although PD-L1-positivity was not significantly correlated with any clinical characteristics including age, sex, smoking/alcoholic history, stage, or differentiation, H-scores for c-Met expression were significantly associated with PD-L1-positivity (OR = 2.34, 95%CI: 1.16-4.72,P= 0.017). PD-L1 expression was not significantly associated with a change in overall survival (P= 0.656). In contrast, the locoregional relapse rate tended to increase (P= 0.134), and the distant metastasis rate was significantly increased (HR = 1.72, 95%CI: 1.01-2.79,P= 0.028) in patients with PD-L1-positive ESCC compared to those with PD-L1-negative ESCC.
  
  
  CONCLUSIONS
  PD-L1 expression is positively correlated with c-Met expression in ESCC. PD-L1 may play a critical role in distant failure and progression of ESCC.
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Ryul
authors.initials: R
authors.lastname: Kim
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Bhumsuk
authors.initials: B
authors.lastname: Keam
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Dohee
authors.initials: D
authors.lastname: Kwon
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Chan-Young
authors.initials: CY
authors.lastname: Ock
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Miso
authors.initials: M
authors.lastname: Kim
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Hak Jae
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Park
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Kang
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Young Tae
authors.initials: YT
authors.lastname: Kim
authors.affiliation: Ryul Kim, Chan-Young Ock, Miso Kim, Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, South Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D016629:Esophagectomy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019859:Proto-Oncogene Proteins c-met
keywords: Esophageal neoplasm; Prognosis; Programmed death ligand-1 protein; c-Met protein; p16INK4A protein