Aberrant gene expression in epithelial cells of mixed odontogenic tumors

Comparative investigations of odontogenic cells in normally forming teeth a nd tumors may provide insights into the mechanisms of the differentiation p rocess. The present study is devoted to late phenotypic markers of amelobla st and odontoblast cells, i.e., proteins involved in biomineralization. The in situ expression of amelogenins, keratins, collagens type III and IV, vi mentin, fibronectin, osteonectin, and osteocalcin was performed on normal a nd tumor odontogenic human cells. The pattern of protein expression showed some similarities between ameloblasts and odontoblasts present in normally developing human teeth and cells present in neoplastic tissues of ameloblas tic fibroma, ameloblastic fibro-odontomas, and complex odontomas. Amelogeni ns (for ameloblasts) and osteocalcin (for odontoblasts) were detected in ce lls with well-organized enamel and dentin, respectively. In contrast, "mixe d" cells located in epithelial zones of mixed odontogenic tumors coexpresse d amelogenins and osteocalcin, as shown by immunostaining. The presence of osteocalcin transcripts was also demonstrated by in situ hybridization in t hese cells. Keratins and vimentin were detected in the same epithelial zone s. Tumor epithelial cells were associated with various amounts of polymorph ic matrix (amelogenin- and osteocalcin-immunoreactive), depending on the ty pes of mixed tumors. No osteocalcin labeling was found in epithelial tumors . This study confirms that the differentiation of normal and tumor odontoge nic cells is accompanied by the expression of some common molecules. Furthe rmore, the gene products present in normal mesenchymal cells were also show n in odontogenic tumor epithelium. These data may be related to a tumor-spe cific overexpression of the corresponding genes transcribed at an undetecta ble level during normal development and/or to an epithelial-mesenchymal tra nsition proposed to occur during normal root formation. A plausible explana tion for the results is that the odontogenic tumor epithelial cells are rec apitulating genetic programs expressed during normal odontogenesis, but the tumor cells demonstrate abnormal expression patterns for these genes.