Are hypoxia-related proteins associated with the invasiveness of glandular odontogenic cysts? A multicenter study

Abstract

Objective The study aimed to investigate the expression of hypoxia markers associated with invadopodia in glandular odontogenic cysts and to explore an association between this expression with the aggressive biological behaviour of this odontogenic cyst. Design Immunohistochemistry was employed to assess the expression of hypoxia-inducible factor 1 alpha (HIF-1α), notch homologous protein of the neurogenic locus 1 (NOTCH-1), disintegrin and metalloproteinase-12 (ADAM-12), and heparin-binding epidermal growth factor (HB-EGF) in 17 samples of glandular odontogenic cysts, 10 samples of calcifying odontogenic cysts, and 10 samples of dental follicles. Results The glandular odontogenic cyst samples exhibited increased expression of HIF-1α, NOTCH-1, ADAM-12 and HBEGF proteins compared with calcifying odontogenic cyst and dental follicle samples. HIF-1α demonstrated localization primarily within the nuclei of cystic epithelial cells of the glandular odontogenic cyst. NOTCH-1 and ADAM-12 exhibited expression in the cytoplasm and nuclei of epithelial and mucous cells of the glandular odontogenic cyst, of whereas HB-EGF was predominantly expressed in the cytoplasm. Weak labeling of these proteins was observed in the odontogenic epithelium of the calcifying odontogenic cyst and dental follicle samples. Conclusions The hypoxia-related signaling proteins are overexpressed in glandular odontogenic cyst when compared with calcifying odontogenic cyst and dental follicle. The reported aggressiveness of glandular odontogenic cyst can be partially explained by the expression of these proteins.