REVIEW ARTICLE: Current concepts of ameloblastoma pathogenesis

Abstract

Ameloblastoma is a locally destructive and invasive tumour that can recur despite adequate surgical removal. Molecular studies have offered interesting findings regarding ameloblastoma pathogenesis. In the present review, the following topics are discussed regarding its molecular nature: clonality, cell cycle proliferation, apoptosis, tumour suppressor genes, ameloblastin and other enamel matrix proteins, osteoclastic mechanism and matrix metalloproteinases and other signalling molecules. It is clear from the literature reviewed that translational studies are necessary to identify prognostic markers of ameloblastoma behaviour and to establish new diagnostic tools to the differential diagnosis of unicystic from multicystic ameloblastoma. Finally, molecular biology studies are also important to develop more effective alternative approaches to the treatment of this aggressive odontogenic tumour.

Molecular etiopathogenesis of ameloblastoma – current concepts revisited

“…Toyosawa et al, (2000) reported potential mutations in ameloblast transcript although these mutations may not be primarily related to the development of AB. [3] Perdigao et al, (2004) also found an association of mutation in amleoblastin gene in epithelial odontogenic tumors. The exact mechanism of tumor formation in mutant mice is unclear but due to defi ciency of ameloblastin there may be deregulation of ameloblast diff erentiation which might be the likely cause of the tumor.…”

“…The exact mechanism of tumor formation in mutant mice is unclear but due to defi ciency of ameloblastin there may be deregulation of ameloblast diff erentiation which might be the likely cause of the tumor. [3] Molecules Involved In Cell Cycle Proliferation Ki-67 Florescu et al, (2012) in their study observed an increased expression of Ki-67 in peripheral cells of tumor islands when compared to the central cells suggesting that the peripheral cells are more proliferative. Ki-67 indices were similar in both UA and SA, despite some diff erence in various subtypes: highest values in the luminal UA which could be attributed to the presence of less number of stellate reticulum-like cells when compared to other subtypes, and consequently, most of the cells counted corresponded to basal, and parabasal layers which are more prone to be positive.…”

“…Increased apoptotic cell death in keratinizing cells in acanthomatous AB, granular cells in granular cell AB variants and neoplastic cells of ameloblastic carcinoma was found suggesting their role in cytodiff erentiation and malignant transformation of odontogenic epithelium. [3] Luo et al, (2006) studied the expression of the Fas/FasL and concluded that it might have a role in the disposal of terminally diff erentiated or degenerative tumor cells in ABs. Many studies conducted on apoptosis demonstrated that anti-apoptotic proteins (bcl-2) and cell proliferation markers (Ki-67) were expressed in the peripheral basal cell layers of ABs, which might be the reason for their progression.…”

“…However, the sequence of events remains unknown. [3] Stem Cell Related Molecules Kumamoto et al, (2010) analyzed the expression of stem cell related molecules (Bmi-1, CD133, and ATP-binding cassette subfamily G member 2 [ABCG2]) in ameloblastic tumors and in tooth germs. Positive expression of CD133 and Bmi-1 was observed in odontogenic epithelial cells adjacent to basement membrane in tooth germs, ABs, and metastasizing ABs, and most of the neoplastic cells in clear cell odontogenic carcinomas and ameloblastic carcinomas showed reactivity for CD133 and Bmi-1.…”

Surgical management of an odontogenic tumor in a banded Gila monster (Heloderma suspectum cinctum) with a novel herpesvirus

“…Similarly, evaluation of an aspirate and incisional biopsy in the present case was more consistent with squamous cell carcinoma. Incisional biopsies are not always accurate and cases may require examination of multiple sections from different areas within the tumor for diagnosis (Gomes et al 2010). In the case of odontogenic tumors, however, the progression and management are similar for most variations.…”