Immunohistochemical assessment of hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CA IX) in ameloblastomas

Objective: To investigate roles of hypoxia-related proteins in odontogenic tumors, we analyzed the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α) and carbonic anhydrase IX (CA IX) and compared with angiogenesis. Methods: 10 dental follicles and 67 ameloblastomas were immunohistochemically examined with antibodies against HIF-1α CA IX, and CD34. Results: Immunohistochemical reactivity for HIF-1α and CA IX was detected in odontogenic epithelial cells, as well as in several macrophages and fibroblasts, in dental follicles and ameloblastomas. HIF-1α was positive in 8 of 10 dental follicles, 45 of 48 primary ameloblastomas, and all 19 recurrent ameloblastomas. Increased HIF-1α reactivity was often found in keratinizing cells in acanthomatous ameloblastomas. Immunoreactivity for CA IX was detected in all samples of dental follicles and primary and recurrent ameloblastomas. CA IX reactivity was significantly higher in ameloblastomas than in dental follicles, in solid ameloblastomas than in unicystic ameloblastomas, and in follicular ameloblastomas than in plexiform ameloblastomas. Acanthomatous ameloblastomas showed increased CA IX reactivity around keratinizing areas, while granular cell ameloblastomas showed increased reactivity in peripheral non-granular cells. Microvessel density (MVD) of CD34-positive capillaries in solid ameloblastomas was significantly higher than in unicystic ameloblastomas. MVD tended to be greater in follicular ameloblastomas than in plexiform ameloblastomas, in granular cell ameloblastomas than in other subtypes of ameloblastomas, and in mural unicystic ameloblastomas than in other types of unicystic ameloblastomas. Conclusions: Our data suggest that hypoxia-related molecules and angiogenesis play a role in tumorigenesis, tissue structuring, cell differentiation, and prognosis of ameloblastomas in the intraosseous microenvironment.