title: HIF-1α, VEGF, and EGFR: contributing factors in the pathogenesis of necrotizing sialometaplasia.
abstract: OBJECTIVE
  Necrotizing sialometaplasia (NS) is an uncommon reactive lesion involving the minor salivary glands. This study aimed to investigate the expression of hypoxia-inducible factor alpha (HIF-1α), vascular endothelial growth factor (VEGF), and epithelial growth factor receptor (EGFR) in the pathogenesis of NS.
  
  
  METHODS
  Paraffin-embedded tissue sections from 10 cases of NS were immunohistochemically stained for HIF-1α, VEGF, and EGFR. A semiquantitative morphometric analysis was performed and compared with normal palatal salivary glands and traumatic ulcerations.
  
  
  RESULTS
  Hypoxia-inducible factor alpha staining was observed in most elements of the affected area, the acini and ducts of the involved salivary glands as well as in the inflammatory infiltrate, the endothelial cells, and stromal cells. HIF-1α was almost absent in the control glands (P < 0.0001). VEGF staining was positive in the stromal capillaries and in the inflammatory infiltrate. The expression was higher in cases of NS compared with the normal salivary glands (P < 0.001). EGFR was expressed in the surface epithelium, the pseudo-epitheliomatous hyperplasia, and the islands of squamous metaplasia. VEGF expression in traumatic ulcerations was lower than that in cases of NS.
  
  
  CONCLUSIONS
  This study provides molecular evidence to the role of hypoxia in NS; HIF-1α, the main regulator of hypoxia, was expressed in the infarcted salivary glands, EGFR in the metaplastic epithelium and VEGF in the stromal capillaries, all three components are the key factors induced by hypoxia.
authors.affiliation: Department of Oral Pathology & Oral Medicine, Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: I
authors.initials: I
authors.lastname: Allon
authors.forename: I
authors.initials: I
authors.lastname: Kaplan
authors.forename: D M
authors.initials: DM
authors.lastname: Allon
authors.forename: H
authors.initials: H
authors.lastname: Vered
authors.forename: B
authors.initials: B
authors.lastname: Shlomi
authors.forename: A
authors.initials: A
authors.lastname: Hirshberg
mesh_terms: D000328:Adult; D000368:Aged; D066246:ErbB Receptors / Q000502:physiology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D012469:Salivary Glands / Q000737:chemistry; D012797:Sialometaplasia, Necrotizing / Q000209:etiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: epithelial growth factor receptor (EGFR); hypoxia; hypoxia-inducible factor alpha (HIF-1α); necrotizing sialometaplasia; vascular endothelial growth factor (VEGF)