title: Paracrine loops of keratinocyte stimulation in cholesteatoma tissue: an immunofluorescence, transmission electron microscopy, and molecular study.
abstract: OBJECTIVE
  In relation to the keratinocyte growth factor (KGF) expression in cholesteatoma tissue, the inflammatory infiltrate present in this disease could play a relevant role in the paracrine stimulation of keratinocytes.
  
  
  BACKGROUND
  Cholesteatoma is a temporal bone pathologic disease characterized by active proliferation of epithelial cells, with progressive growth and involvement of the neighboring middle/inner ear structures. The pathogenetic mechanism underlying the hyperproliferation of keratinocytes is not yet fully clarified. It has been suggested that keratinocyte proliferation and migration could be mediated by several autocrine and paracrine growth factors and their receptors. A previous study has reported that the expression of KGF receptor is increased in more differentiated areas of the cholesteatoma tissue, whereas the expression of the epidermal growth factor receptor is associated with proliferative and migratory areas of the lesion.
  
  
  METHODS
  Fresh cholesteatoma samples were collected during surgical procedures. Serial cryosections were examined by conventional hematoxylin and eosin or by immunofluorescence with antipancytokeratin antibodies. The ultrastructural features were analyzed by transmission electron microscopy. The expression of KGF, K1, and filaggrin in the samples was evaluated by quantitative reverse transcription-polymerase chain reaction and correlated with the dermal degree of inflammatory infiltrate and the presence of stromal cells.
  
  
  RESULTS
  Increased expression of KGF was associated with strong levels of the inflammatory infiltrate.
  
  
  CONCLUSIONS
  These results would suggest that KGF up-modulation is a consequence of fibroblast stimulation by inflammatory cells and that this paracrine loop could be responsible not only for the hyperproliferation of keratinocytes in cholesteatoma tissue but also for the deregulation of epidermal differentiation.
authors.affiliation: Department of Clinical and Molecular Medicine, Cellular Diagnostic Unit, II Medical School Sapienza University, Sant'Andrea Hospital, Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: d'Alessandro
authors.forename: Salvatore
authors.initials: S
authors.lastname: Raffa
authors.forename: Carmelo
authors.initials: C
authors.lastname: Murè
authors.forename: Daniela
authors.initials: D
authors.lastname: Kovacs
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Torrisi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Barbara
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D018424:Cholesteatoma, Middle Ear / Q000235:genetics / Q000473:pathology*; D004247:DNA / Q000235:genetics; D017931:DNA Primers; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000096:biosynthesis / Q000235:genetics; D005347:Fibroblasts / Q000473:pathology; D000091344:Filaggrin Proteins; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000096:biosynthesis / Q000235:genetics; D015603:Keratinocytes / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D019899:Paracrine Communication / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000473:pathology
chemical_list: D017931:DNA Primers; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D051523:Fibroblast Growth Factor 7; D012313:RNA; D004247:DNA