Expression of apoptosis-related proteins in various cellular components of ameloblastomas

Objectives:The present study was to evaluate the expression pattern of apoptosis-related proteins in different histologic subtypes and various cellular components of ameloblastomas. Methods: By immunohistochemical method, expression of Fas, Fas-ligand (FasL), caspase-3, Bcl-2 and Ki67 were examined in 39 cases of ameloblastoma (27 follicular and 12 plexiform ameloblastomas). Staining intensity of Fas, FasL, caspase-3 and Bcl-2 in the four types of tumor cellular components, i.e. peripheral columnar basal cells of tumor nests, central stellate reticulum-like cells, foci of squamous and granular cells was scored using a semi-quantitative scale, and comparisons were made statistically. Apoptotic cells were examined in 11 cases of ameloblastoma (9 follicular and 2 plexiform tumors) using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method (TUNEL). Results: Expression of pro-apoptotic proteins, Fas, FasL and caspase-3 was detected in majority of the cases, with a similar pattern showing strong staining in the foci of squamous metaplasia and granular cells usually situated in the central area of tumor islands, irrespective of histologic subtypes. In contrast, expression of anti-apoptotic protein, Bcl-2 and proliferating marker Ki67 were predominantly seen in the peripheral basal cell layer of tumor islands. There were significant differences in the staining intensity of Fas, caspase-3 and Bcl-2 among the four types of tumor cells. In general, apoptotic cells detected by TUNEL were scanty in ameloblastomas and almost exclusively found in the foci of squamous and granular cells. Conclusion: The present study demonstrated the differential expression of apoptosis-related proteins in various cellular components of ameloblastomas, with pro-apoptotic proteins and apoptotic cells being closely associated with squamous metaplasia and granular transformation of the tumor cells. These results suggest that Fas-FasL induced apoptotic cell death may function in the disposal of terminally differentiated or degenerative tumor cells in ameloblastomas.