Migaldi M, Sartori G, Rossi G, Cittadini A, Sgambato A
Dipartimento Misto di Anatomia Patologica e di Medicina Legale, Sezione di Anatomia Patologica, University of Modena and Reggio Emilia, Modena, Italy.
Oral Oncol. 2008 Jan;44(1):50-60. doi: 10.1016/j.oraloncology.2006.12.004. Epub 2007 Feb 16.
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.
成釉细胞瘤是最常见的牙源性肿瘤。它可呈现多种组织学模式，具有很强的浸润潜能和高复发率。微卫星序列突变是肿瘤转化的一个标志，但关于它们在成釉细胞瘤发生发展中的作用知之甚少。在本研究中，从24例成釉细胞瘤的激光显微切割样本中提取DNA，并分析22个微卫星位点的状态。评估微卫星改变的发生情况和模式，以缺失或长度变异的形式，并将其与Ki67标记指数及其他临床病理参数相关联。还评估了这些改变的预后意义。高Ki67表达与较短的无病生存期显著相关（对数秩检验p = 0.003）。在所分析的所有（100%）成釉细胞瘤中均观察到至少一个所选位点的改变，每个肿瘤平均有4个微卫星改变。最常改变的微卫星是D9S747和D11S488（42%）。分析的所有其他位点在不到40%的病例中发生改变，其中一些位点（D3S1312、D3S1300、IFNA、D9S164、D13S176和TP53）在所分析的任何成釉细胞瘤中均未显示改变。未观察到微卫星改变的发生与其他参数之间的关系，如患者年龄和性别、肿瘤大小、位置和组织类型。微卫星改变在显示高Ki67标记指数的肿瘤中更频繁发生（p = 0.03），在单变量分析中是疾病复发风险增加的预测指标（对数秩检验p = 0.039）。这些发现表明微卫星改变在成釉细胞瘤中是常见事件。它们还表明，评估肿瘤细胞增殖活性和微卫星改变可能有助于对成釉细胞瘤进行预后分层，并预测这些肿瘤的临床行为。
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