title: Increased permeability of the epithelium of middle ear cholesteatoma.
abstract: OBJECTIVE
  We investigated the electrical impedance of and the expressions of tight junction molecules in the cholesteatoma epithelium to provide supporting evidence for the acid lysis theory of bone resorption in middle ear cholesteatoma.
  
  
  METHODS
  Study subjects were patients with primary acquired middle ear cholesteatoma and those with non-cholesteatomatous chronic otitis media who underwent tympanomastoidectomy. The electrical impedance of the cholesteatoma epithelium was measured during tympanomastoidectomy by loading alternating currents of 320 Hz and 30.7 kHz. The expressions of tricellulin (MARVELD2), claudin-1 (CLDN1) and claudin-3 (CLDN3) were examined by fluorescence immunohistochemistry and quantitative reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  The electrical impedance of the cholesteatoma epithelium was significantly lower than that of the post-auricular skin and external auditory canal skin at both 320 Hz and 30.7 kHz. Immunoreactivity for MARVELD2, CLDN1 and CLDN3 was localised mainly in the granular layer, and to lesser degree, in the horny and spinous layers in both the cholesteatoma tissue and post-auricular skin. Fluorescence intensity was moderate for MARVELD2, weak for CLDN1 and strong for CLDN3. The expressions of MARVELD2, CLDN1 and CLDN3 mRNA were significantly lower in the cholesteatoma tissue than in the post-auricular skin.
  
  
  CONCLUSIONS
  These results indicate the increased permeability of the cholesteatoma epithelium and suggest that this change is, at least partially, dependent on the decrease in the expressions of the tight junction molecules. This evidence supports the acid lysis hypothesis of bone resorption in cholesteatoma.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Occupational and Environmental Health, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Koizumi
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Ohbuchi
authors.forename: T
authors.initials: T
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Hashida
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D001862:Bone Resorption; D016022:Case-Control Studies; D018424:Cholesteatoma, Middle Ear / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism*; D062465:Claudin-3 / Q000235:genetics / Q000378:metabolism*; D017097:Electric Impedance; D004848:Epithelium / Q000378:metabolism*; D006801:Humans; D062794:MARVEL Domain Containing 2 Protein / Q000235:genetics / Q000378:metabolism*; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; D012333:RNA, Messenger