title: Relation of epidermal growth factor receptor expression to goblet cell hyperplasia in nasal polyps.
abstract: BACKGROUND
  Because the epidermal growth factor receptor (EGFR) system regulates mucin production in airway epithelium, we hypothesized a role for this system in mucus hypersecretion that occurs in nasal polyposis.
  
  
  OBJECTIVE
  We examined the relationship between goblet cell hyperplasia, EGFR expression, and inflammatory mediators produced by eosinophils and neutrophils in nasal polyp tissues.
  
  
  METHODS
  Nasal polyp tissue samples from 8 patients and nasal turbinate biopsy specimens from 6 normal control subjects were examined for alcian blue/PAS staining, mucin MUC5AC (MUC5AC), and EGFR immunoreactivity and EGFR gene expression (in situ hybridization). We also examined the role of eosinophils and neutrophils in goblet cell hyperplasia.
  
  
  RESULTS
  In control nasal mucosa alcian blue/periodic acid-Schiff- and MUC5AC-stained areas were 18.40% +/- 1.31% and 21.89% +/- 1.43%, respectively. In polyps the alcian blue/periodic acid-Schiff- and MUC5AC-stained areas were 51.30% +/- 5.85% and 52.07% +/- 6.58%, which was significantly larger than that found in control subjects (each comparison, P <.01). Four of 6 control specimens expressed EGFR messenger RNA and protein weakly in the epithelium. In polyps 4 of 8 specimens expressed EGFR gene and EGFR protein strongly; the EGFR-stained area was greater in hyperplastic than in pseudostratified epithelium. TNF-alpha immunoreactivity, expressed in eosinophils, was increased in EGFR-positive polyps compared with EGFR-negative polyps, suggesting a role for TNF-alpha in EGFR expression. Neutrophils were increased in the epithelium of EGFR-positive compared with EGFR-negative polyps, suggesting a role for these cells in mucin expression and in goblet cell degranulation.
  
  
  CONCLUSIONS
  These data suggest a role for EGFR cascade in the regulation of goblet cell mucins in nasal polyps. Proof of concept will require clinical studies using selective EGFR inhibitors.
authors.affiliation: Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California San Francisco, San Francisco, CA 94143-0130, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Burgel
authors.forename: E
authors.initials: E
authors.lastname: Escudier
authors.forename: A
authors.initials: A
authors.lastname: Coste
authors.forename: T
authors.initials: T
authors.lastname: Dao-Pick
authors.forename: I F
authors.initials: IF
authors.lastname: Ueki
authors.forename: K
authors.initials: K
authors.lastname: Takeyama
authors.forename: J J
authors.initials: JJ
authors.lastname: Shim
authors.forename: A H
authors.initials: AH
authors.lastname: Murr
authors.forename: J A
authors.initials: JA
authors.lastname: Nadel
mesh_terms: D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D020397:Goblet Cells / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D009077:Mucins / Q000235:genetics; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology*; D009504:Neutrophils / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: D009077:Mucins; D014409:Tumor Necrosis Factor-alpha; D066246:ErbB Receptors