title: The role of beta-catenin signaling in the malignant potential of cystitis glandularis.
abstract: OBJECTIVE
  Chronic inflammation is a risk factor for malignant transformation in the bladder. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) is a mediator of such inflammation that induces nuclear localization of the adherens junction component beta-catenin. This mechanism has a key role in the initiation and progression of the premalignant lesion Barrett's metaplasia of the esophagus. Cystitis glandularis is a metaplastic lesion of the bladder urothelium occurring in the presence of chronic inflammation and in up to 13% of asymptomatic bladders. Two subtypes are described (typical and intestinal/colonic) with uncertain malignant potential. Etiologically and histologically cystitis glandularis mimics Barrett's metaplasia. We investigated the roles of beta-catenin and TNFalpha in cystitis glandularis.
  
  
  METHODS
  Immunohistochemistry and immunofluorescence were used to demonstrate the expression and localization of E-cadherin, beta-catenin and TNFalpha in 9 sections of typical cystitis glandularis and 4 of intestinal/colonic cystitis glandularis. Appropriate controls were used for all experiments.
  
  
  RESULTS
  Immunohistochemistry demonstrated normal membranous expression of E-cadherin and beta-catenin in all cystitis glandularis sections with increased TNFalpha expression. Immunofluorescence showed nuclear localization of beta-catenin in the intestinal/colonic subtype only, which was not observed in typical cystitis glandularis.
  
  
  CONCLUSIONS
  The presence of nuclear beta-catenin suggests that intestinal/colonic cystitis glandularis shares the same signaling pathway with the premalignant lesion Barrett's metaplasia of the esophagus and the intestinal/colonic subtype of cystitis glandularis may have the potential to progress to malignancy. This finding has important implications for the management of this lesion.
authors.affiliation: Epithelial Laboratory, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, UK.
authors.forename: R T
authors.initials: RT
authors.lastname: Bryan
authors.forename: J H
authors.initials: JH
authors.lastname: Nicholls
authors.forename: R F
authors.initials: RF
authors.lastname: Harrison
authors.forename: J A
authors.initials: JA
authors.lastname: Jankowski
authors.forename: D M A
authors.initials: DM
authors.lastname: Wallace
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002467:Cell Nucleus / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology; D003556:Cystitis / Q000473:pathology / Q000503:physiopathology*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D018450:Disease Progression; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D008679:Metaplasia; D008856:Microscopy, Fluorescence; D011230:Precancerous Conditions / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000503:physiopathology*; D019459:Urothelium / Q000473:pathology; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin