title: The clinicopathological significance of Lgr5 expression in lung adenocarcinoma.
abstract: BACKGROUND
  The leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), also known as Gpr49, has been identified as a marker of crypt basal columnar stem cells along the gastrointestinal tract and of bulge stem cells in the hair follicle. The aims of this study were to immunohistochemically examine Lgr5 expression in surgically resected non-small cell lung carcinomas (NSCLC), and evaluate the relationships between Lgr5 expression and the clinicopathological parameters and prognosis of patients.
  
  
  METHODS
  Lgr5 expression was immunohistochemically studied in 266 consecutive resected NSCLCs, and its associations with clinicopathological parameters including TTF-1 and CDX-2 expressions were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of Lgr5 expression on survival.
  
  
  RESULTS
  Lgr5 was detected only in tumors with adenocarcinoma histology, and 16 cases were judged as positive. Among lung adenocarcinomas, Lgr5 expression was significantly associated with a larger tumor size (> 5 cm) (P = 0.033), higher pathological TNM stage of the disease (stage II and III) (P = 0.025), TTF-1-negative adenocarocinoma (P = 0.042), and poorer prognosis (P = 0.026). However, Lgr5 expression was not an independent predictor of poorer survival after controlling for clinicopathological factors.
  
  
  CONCLUSIONS
  The present study reveals that Lgr5 is expressed in a subset of lung adenocarcinoma, and its expression is related to some clinicopathological parameters and a poorer prognosis, although further studies are required to clarify the biological function of Lgr5 in lung adenocarcinoma.
authors.affiliation: Department of Respiratory Medicine, School of Medicine, Kitasato University, Kanagawa, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ryuge
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sato
authors.forename: Shi-Xu
authors.initials: SX
authors.lastname: Jiang
authors.forename: Guoqin
authors.initials: G
authors.lastname: Wang
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Ryo
authors.initials: R
authors.lastname: Nagashio
authors.forename: Ken
authors.initials: K
authors.lastname: Katono
authors.forename: Akira
authors.initials: A
authors.lastname: Iyoda
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Satoh
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Masuda
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D014157:Transcription Factors; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled; C504003:TTF1 protein, human; D014157:Transcription Factors
keywords: CSC; Cancer stem cell; EREG; HR; Immunohistochemistry; Lgr5; Lung adenocarcinoma; NSCLC; Prognostic marker; TRU; cancer stem cell; epiregulin; hazard ratio; leucine-rich repeat-containing G-protein-coupled receptor 5; non-small cell lung cancer; p-TNM; pathological TNM; terminal respiratory unit