title: High Frequency of Programmed Death-ligand 1 Expression in Emphysematous Bullae-associated Lung Adenocarcinomas.
abstract: Emphysematous bullae (EB) are known to be associated with a high incidence of lung cancer; however, the reason for this has yet to be elucidated. The objective of the present study was to clarify the prevalence of programmed death-ligand-1 (PD-L1) expression in EB-associated lung adenocarcinomas.
  
  
  
  A total of 369 patients with resected lung adenocarcinoma whose preoperative computed tomography findings were available for the examination of EB were analyzed for PD-L1 expression by immunohistochemistry and evaluated to determine the association between PD-L1 expression and EB-related adenocarcinomas.
  
  
  
  Among 369 patients, EB and cancer adjoining EB (Ca-ADJ) were identified in 81 (22.0%) and 50 (13.6%) patients, respectively. EB and Ca-ADJ were significantly associated with male gender, a smoking habit, a decreased forced expiratory volume in 1 second, a relatively higher tumor grade, advanced T status and stage, the presence of pleural and vessel invasion, invasive pathologic subtypes, and wild-type epidermal growth factor receptor. Seventy patients (19.0%) were positive for PD-L1 expression, whereas the remaining 299 patients (81.0%) were negative. Thirty-six (44.4%) and 29 (58.0%) of 81 and 50 patients with EB and Ca-ADJ, respectively, were positive for PD-L1 expression, which was shown to be significant by the Fisher exact test (P < .001 and P < .001, respectively). Among the 81 lung adenocarcinomas with EB, Ca-ADJ was significantly associated with PD-L1 expression (P = .021). In a multivariate analysis, the presence of Ca-ADJ was found to be an independent predictor of PD-L1 expression.
  
  
  
  EB-associated lung adenocarcinomas express PD-L1 protein more frequently than those without EB.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: gouji104kawa@gmail.com.
authors.forename: Gouji
authors.initials: G
authors.lastname: Toyokawa
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takada
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Okamoto
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kozuma
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Haratake
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shinkichi
authors.initials: S
authors.lastname: Takamori
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Akamine
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Katsura
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Shoji
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D001768:Blister / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011656:Pulmonary Emphysema / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D012189:Retrospective Studies; D012737:Sex Factors; D012907:Smoking; D014057:Tomography, X-Ray Computed
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D066246:ErbB Receptors
keywords: Emphysematous bullae; Lung adenocarcinoma; Programmed death-ligand 1; Surgery