HIF-1α, VEGF, and EGFR: contributing factors in the pathogenesis of necrotizing sialometaplasia

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.

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.

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.

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.