title: Toll-like receptor 9 is a novel biomarker for esophageal squamous cell dysplasia and squamous cell carcinoma progression.
abstract: BACKGROUND
  Stimulation of Toll-like receptor 9 (TLR9) has been linked to invasion in various cancer cells in vitro. We investigated TLR9 expression in normal, dysplastic and malignant esophageal squamous epithelium.
  
  
  METHODS
  TLR9 expression was analyzed by immunohistochemistry in 46 cases of esophageal squamous cell carcinoma, including 12 cases with adjacent squamous dysplasia and 24 cases with normal esophageal epithelium. TLR9 expression was compared with tumor grade, stage, proliferation, apoptosis and vascular density.
  
  
  RESULTS
  In normal esophageal squamous epithelium, TLR9 staining intensity decreased linearly from the basal layers to the superficial layers (p < 0.001). Strong TLR9 expression was detected across full thickness of high-grade dysplasia, the intensity clearly differing from the normal squamous epithelium and squamous cell carcinoma (p < 0.001). All squamous cell carcinomas exhibited TLR9 expression that was positively associated with a high grade (p < 0.05), the presence of lymph node metastases (p < 0.05) and previously undetected distant metastases (p < 0.05).
  
  
  CONCLUSIONS
  Expression of TLR9 in the basal parts of normal esophageal epithelium suggests a role related to cell proliferation and differentation. TLR9 upregulation detected in dysplastic epithelium and in disseminated carcinomas indicates that this protein may serve as a novel marker for esophageal squamous dysplasia and carcinoma with metastatic potential.
authors.affiliation: Department of Surgery, University of Oulu, Oulu, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Takala
authors.forename: Joonas H
authors.initials: JH
authors.lastname: Kauppila
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.forename: Katri S
authors.initials: KS
authors.lastname: Selander
authors.forename: Katri S
authors.initials: KS
authors.lastname: Vuopala
authors.forename: Petri P
authors.initials: PP
authors.lastname: Lehenkari
authors.forename: Juha
authors.initials: J
authors.lastname: Saarnio
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
mesh_terms: D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D003937:Diagnosis, Differential; D018450:Disease Progression; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004935:Esophageal Diseases / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004947:Esophagus / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D011230:Precancerous Conditions; D011379:Prognosis; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D051217:Toll-Like Receptor 9