Expression of MMPs and TIMPs was considered to be associated with interactions between epithelial cells and mesenchymal components in normal and neoplastic odontogenic tissues; these molecules might play a role in regulation of tumor progression in ameloblastomas as well as regulation of developmental processes in tooth germs.

We conclude that COCs with various histological features have neoplastic potential and may not be separate entities within the same histological spectrum.

Diverse types of epithelial odontogenic tumors express amelogenin and CK19, suggesting that these tumors have ameloblastic differentiation or odontogenic epithelial properties.

Immunohistochemical localization of HGF, TGF-beta and their receptors in tooth germs and epithelial odontogenic tumors supports the hypothesis that HGF and TGF-beta act on epithelial cells via paracrine and autocrine mechanisms. Altered expression of the agents in these epithelial odontogenic tumors, especially subtypes of ameloblastomas, AOTs and COCs, suggests that HGF and TGF-beta signaling might affect differentiation of neoplastic odontogenic epithelial cells. Activated HGF/c-Met pathway and reduced TGF-beta signaling in CCOTs and ameloblastic carcinomas may be associated with the malignant potential of these epithelial odontogenic tumors.

Benign mixed and mesenchymal odontogenic tumors (ameloblastic fibroma, ameloblastic fibrodentinoma, ameloblastic fibro-odontomas, odontogenic fibroma and odontogenic myxoma) were immunohistochemically examined using antibodies against amelogenin, cytokeratin 19, bcl-2, hepatocyte growth factor (HGF), c-Met, transforming growth factor-b (TGF-b), TGF-b receptors and Ki-67 to know cytodifferentiation, epithelial-mesenchymal interaction and proliferative activity. Expression of amelogenin was detected in odontogenic epithelial cells and enamel matrices in ameloblastic fibro-odontomas, and cytokeratin 19 was expressed in odontogenic epithelial cells, indicating odontogenic epithelial properties. Expressions of bcl-2, HGF, TGF-b, TbR I and TbR II were detected in odontogenic epithelial and mesenchymal cells in mixed and mesenchymal odontogenic tumors, while expression of c-Met was detected in odontogenic epithelial cells. Odontogenic epithelial and mesenchymal cells sporadically showed positive reactions for Ki-67 in mixed and mesenchymal odontogenic tumors, and no apparent differences were obtained among these tumors or between the components. Conclusion: Immunohistochemical localization of HGF, TGF-b and their receptors suggests that these growth factor signaling are effective in the epithelial component in paracrine and autocrine manner in mixed and mesenchymal odontogenic tumors. These results of growth factor signaling suggest that certain epithelial-mesenchymal interactions are related to neoplastic cell growth in these tumors.