title: Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett's esophagus, dysplasia and adenocarcinoma.
abstract: BACKGROUND
  Toll-like receptors (TLRs) recognize microbial and endogenous ligands and have already shown to play a role in esophageal cancer. In this study, we evaluated especially TLRs that sense bacterial cell wall components in Barrett's esophagus, dysplasia and esophageal adenocarcinoma.
  
  
  METHODS
  TLRs 1, 2, 4 and 6 were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal dysplasia (n = 30) or adenocarcinoma (n = 99). Structures and lesions were evaluated including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37), and esophageal adenocarcinoma (n = 99).
  
  
  RESULTS
  We found TLR1, TLR2, TLR4 and TLR6 expression in all lesions. TLR expression increased in Barrett's mucosa and dysplasia. There was profound increase of TLR expression from gastric- to intestinal-type columnar epithelium. In cancers, high nuclear and cytoplasmic staining of TLR4 associated with metastatic disease and poor prognosis.
  
  
  CONCLUSIONS
  TLR1, TLR2, TLR4 and TLR6 are upregulated during malignant changes of esophageal columnar epithelium. Increased TLR4 expression associates with advanced stage and poor prognosis in esophageal adenocarcinoma.
authors.affiliation: Department of Pathology, University of Oulu, 90014 Oulu, Finland.|Department of Surgery, University of Oulu, 90014 Oulu, Finland.|Medical Research Center Oulu, 90014 Oulu, Finland.|Oulu University Hospital, 90029 Oulu, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Huhta
authors.affiliation: Department of Pathology, University of Oulu, 90014 Oulu, Finland.|Department of Surgery, University of Oulu, 90014 Oulu, Finland.|Medical Research Center Oulu, 90014 Oulu, Finland.|Oulu University Hospital, 90029 Oulu, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Helminen
authors.affiliation: Department of Surgery, University of Oulu, 90014 Oulu, Finland.|Department of Anatomy and Cell Biology, University of Oulu, 90014 Oulu, Finland.|Medical Research Center Oulu, 90014 Oulu, Finland.|Oulu University Hospital, 90029 Oulu, Finland.
authors.forename: Petri P
authors.initials: PP
authors.lastname: Lehenkari
authors.affiliation: Department of Surgery, University of Oulu, 90014 Oulu, Finland.|Medical Research Center Oulu, 90014 Oulu, Finland.|Oulu University Hospital, 90029 Oulu, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Saarnio
authors.affiliation: Department of Pathology, University of Oulu, 90014 Oulu, Finland.|Medical Research Center Oulu, 90014 Oulu, Finland.|Oulu University Hospital, 90029 Oulu, Finland.
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
authors.affiliation: Department of Pathology, University of Oulu, 90014 Oulu, Finland.|Department of Surgery, University of Oulu, 90014 Oulu, Finland.|Medical Research Center Oulu, 90014 Oulu, Finland.|Oulu University Hospital, 90029 Oulu, Finland.
authors.forename: Joonas H
authors.initials: JH
authors.lastname: Kauppila
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D051194:Toll-Like Receptor 1 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051216:Toll-Like Receptor 6 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495368:TLR6 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6
keywords: Toll-like receptor 1; Toll-like receptor 2; Toll-like receptor 4; Toll-like receptor 6; esophageal adenocarcinoma