Notch Expression Patterns and Ameloblastoma Phenotypes

Background: Notch gene family encodes four receptors (Notch1-4) that are involved in diverse processes including odontogenesis. Dysregulation of this signaling pathway has been implicated in tumorigenesis but its role during the development and progression of ameloblastoma remains unclear. Objective: To explore the existence of a correlation between Notch expression and ameloblastoma phenotypes. Methods: Notch receptors (1, 2, 3 and 4) and ligands (Jagged1, 2 and Delta1) were examined immunohistochemically in unicystic (UA, n=22), solid/multicystic (SA, n=23) and recurrent ameloblastoma (RA, n=19). Results: Notch4 showed high expression in SA (n=19/23; 82.6%) compared to UA (n=1/22; 4.5%) or RA (n=10/19; 52.6%) (p<0.05) suggesting positive correlation between Notch4 signaling pathway and ameloblastomas with a solid/multicystic phenotype. Underexpression of Notch ligands (Jagged1 and Delta1) compared to their receptors (Notch1, 3 and 4) (p<0.05), and nonreactivity for Notch2 and Jagged2 in all 3 subsets suggests that ameloblastoma tumor epithelium belongs to an earlier stage of cellular differentiation (equivalent to the inner enamel epithelium of the developing tooth germ) before lineage commitment. Conclusions: Present findings suggest that Notch signaling molecules play differing roles in the acquisition of different ameloblastoma phenotypes.