Immunohistochemical analysis of apoptosis-related factors (Fas, Fas ligand, caspase-3 and single-stranded DNA) in ameloblastomas

Background: To clarify the possible role of apoptotic cell death in oncogenesis and cytodifferentiation of odontogenic epithelium, apoptosis-related factors - Fas, Fas ligand (FasL), caspase-3 and single-stranded DNA (ssDNA) - were analyzed in ameloblastomas as well as in tooth germs. Methods: Specimens of 5 tooth germs, 29 benign ameloblastomas and 5 malignant ameloblastomas were examined by immunohistochemistry using anti-Fas, FasL, caspase-3 and ssDNA polyclonal antibodies. Results: Immunoreactivity for Fas and FasL was detected in normal and neoplastic odontogenic epithelial cells. Fas expression in ameloblastomas was slightly lower than that in tooth germs, whereas FasL expression was similar in tooth germs and ameloblastomas. Malignant ameloblastomas showed downregulation of Fas expression and upregulation of FasL expression, as compared with benign ameloblastomas, indicating escape from cell death attack by immune cells. Immunoreactivity for caspase-3 was detected chiefly in cells neighboring the basement membrane in tooth germs and ameloblastomas. Expression of caspase-3 and Fas tended to be low in basal cell ameloblastomas and high in desmoplastic ameloblastomas, as compared with other variants of ameloblastomas. Caspase-3 expression was more intense in malignant ameloblastomas than in tooth germs and benign ameloblastomas. Apoptotic bodies reactive with anti-ssDNA antibody were detected in normal and neoplastic odontogenic epithelial cells detached from the basement membrane. Keratinizing cells in acanthomatous ameloblastomas and granular cells in granular cell ameloblastomas showed increased numbers of apoptotic bodies and increased expression of Fas and caspase-3, as compared with other neoplastic cells. Apoptotic reactions in malignant ameloblastomas were less frequent than in benign ameloblastomas, indicating abnormal regulation of cell turnover in odontogenic epithelial cells. Conclusion: These apoptosis-related factors were detected in various patterns in normal and neoplastic odontogenic epithelium, suggesting that these factors might be associated with oncogenesis and cytodifferentiation of epithelial odontogenic tumors.