METHODS: In tooth germs and epithelial
odontogenic tumors, immunoreactivity for HGF and
TGF-beta was detected in both epithelial and mesenchymal cells, while expression of their receptors was found only in epithelial cells. In tooth germs and main types of
ameloblastomas, HGF and
TGF-beta reactivity was marked in epithelial cells near the basement membrane, and their receptors were diffusely positive in most epithelial cells. In subtypes of
ameloblastomas, reduced expression of HGF, c-Met and
TGF-beta and increased reactivity for
TGF-beta receptors were detected in keratinizing cells in acanthomatous
ameloblastomas, and granular cells in granular cell
ameloblastomas demonstrated little or no expression of HGF,
TGF-beta or their receptors. As compared with main types of
ameloblastomas, basal cell
ameloblastomas showed high HGF reactivity, and desmoplastic
ameloblastomas exhibited elevated reactivity for
TGF-beta and its receptors. Neoplastic cells in CEOTs, AOTs and COCs showed reactivity for HGF,
TGF-beta and their receptors. Elevated HGF and
TGF-beta reactivity was found in pseudoglandular cells in AOTs, and high expression of their receptors was noted in ghost cells in COCs. Metastasizing
ameloblastomas showed similar expression patterns of HGF,
TGF-beta and their receptors to those of benign
ameloblastomas, while CCOTs and ameloblastic
carcinomas had increased HGF expression and low reactivity for
TGF-beta and its receptors as compared with benign
ameloblastomas.
CONCLUSIONS: 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.