Expression of cell cycle and apoptosis-related proteins in sporadic odontogenic keratocysts and odontogenic keratocysts associated with the nevoid basal cell carcinoma syndrome

Odontogenic keratocysts are occasionally (4-5%) associated with the nevoid basal cell carcinoma syndrome, a pleiotropic, autosomal disorder presenting a spectrum of developmental abnormalities and a predisposition for the dev elopment of different neoplasms. The aim of this study was to establish whe ther keratocysts showing clinically aggressive behavior associated with nev oid basal cell carcinoma syndrome reflect differences in cellular prolifera tion rate and/or in the expression of oncoproteins and tumor suppressor gen es. For this reason, formalin-fixed paraffin-embedded sections of odontogen ic keratocysts associated with the nevoid basal cell carcinoma syndrome (16 cases) and sporadic odontogenic keratocysts (16 cases) were compared for e xpression of proliferating cell nuclear antigen (PCNA) and p53, bcl-2, and bcl-1 (cyclin D1) once-proteins. Most of the epithelial lining of odontogen ic keratocysts associated with the nevoid basal cell carcinoma syndrome sho wed nuclear immunopositivity for p53 protein and overexpression of cyclin D 1 with various degrees of staining intensity. All sporadic odontogenic kera tocysts were negative for p53 and cyclin D1. The expressions of bcl-2 oncop rotein were found to be substantially similar between the two groups of les ions, with a cytoplasmic immunopositivity localized only in the resting res erve basal layer of the epithelium. PCNA expression showed no statistically significant difference between the two groups of lesions. In conclusion, t he finding of cyclin D1 and p53 overexpression in odontogenic keratocysts a ssociated with the nevoid basal cell carcinoma syndrome could be considered a hallmark of a mutated cellular phenotype, thus leading to the hypothesis that their aggressive clinical behavior could be due to a dysregulation of the expression of cyclin D1 and p53 proteins, involved in a check-point co ntrol of cellular proliferation.