Tumor cell proliferation and microsatellite alterations in human ameloblastoma

Ameloblastoma is the most common odontogenic tumor. It can exhibit a variety of histological patterns, a great infiltrative potential and a high recurrence rate. Mutations in microsatellite sequences are a hallmark of neoplastic transformation but little is known about their role in ameloblastoma development. In this study DNA was extracted from laser-microdissected samples of 24 ameloblastomas and was analyzed for the status of 22 microsatellite loci. The occurrence and the pattern of microsatellite alterations, in form of loss or length variation, was evaluated and correlated with the Ki67 labeling index and with other clinicopathologic parameters. The prognostic significance of these alterations was also evaluated. High Ki67 expression was significantly associated with a shorter disease-free survival (p=0.003 by log-rank test). Alterations of at least one of the selected loci was observed in all (100%) the ameloblastomas analyzed with a mean of 4 altered microsatellites for each tumor. The microsatellites most frequently altered were D9S747 and D11S488 (42%). All the other loci analyzed were altered in less than 40% of cases and some of them (D3S1312, D3S1300, IFNA, D9S164, D13S176 and TP53) did not show alterations in any of the ameloblastomas analyzed. No relationship was observed between the occurrence of microsatellite alterations and other parameters, such as patients age and gender, tumor size, localization and histotype. The occurrence of microsatellite alterations was more frequent in tumors displaying a high Ki67 labeling index (p=0.03) and in a univariate analysis was predictor of an increased risk of disease recurrence (p=0.039 by log-rank test). These findings demonstrate that microsatellite alterations are frequent event in ameloblastomas. They also suggest that evaluation of tumor cells proliferative activity and microsatellite alterations may be helpful to stratify ameloblastomas prognostically and to predict the clinical behavior of these tumors