Detection of cell cycle-related factors in ameloblastomas

To determine whether cell cycle regulation or alteration plays a role in oncogenesis and cytodifferentiation of odontogenic epithelium, cell cycle-related factors, including cyclin D1, p16^INK4a, p21^WAF1/Cip1 and p27^Kip1 proteins, DNA topoisomerase IIα and histone H3 mRNA, were examined in 8 tooth germs and 31 ameloblastomas. Cyclin D1 was expressed in epithelial cells near the basement membrane in tooth germs and ameloblastomas, suggesting that this protein participates in cell proliferation in odontogenic epithelium. Immunoreactivity for p16 protein was observed in most epithelial cells in tooth germs and ameloblastomas. Expression of p21 protein was detected in most epithelial cells in tooth germs and ameloblastomas but not in keratinizing or granular cells in variants of ameloblastomas. Expression of p27 protein was chiefly found in central polyhedral cells and keratinizing cells in tooth germs and ameloblastomas. These cyclin-dependent kinase inhibitors were well preserved in ameloblastomas as compared with tooth germs, suggesting that the odontogenic epithelium is strictly regulated by these factors. The cell cycle phase/cellular proliferation markers, DNA topoisomerase IIα and histone H3 mRNA, were localized in scattered epithelial cells attached to the basement membrane in tooth germs and ameloblastomas.