Department of Oral Biological and Medical Science, the University of British Columbia, 2199 Wesbrook Mall, Vancouver, BC, Canada.
J Dent Res. 2012 Jan;91(1):52-7. doi: 10.1177/0022034511425676. Epub 2011 Oct 11.
Subgroups of patients with oral pre-malignant lesions (OPLs) are at extremely high risk for developing invasive cancer in spite of surgical excision. The objective of this study was to evaluate the utility of specific genes and their associated centromeres as markers to stratify OPLs for their cancer risk. Samples used in this study included 35 oral dysplasia with known outcome and 20 normal oral mucosa. Of the dysplasias, 20 were from an ongoing longitudinal study showing progression. The remaining 15 cases (2 of which progressed) were chosen from the population-based, provincial BC Oral Biopsy Service (OBS). Copy number alterations at EGFR, CEP7, CCND1, and CEP11 were evaluated by fluorescent in situ hybridization (FISH). There was no significant difference in demographics between progressors and non-progressors. Specific FISH profiles at these genes and their corresponding centromeres were associated with progression. High gene gain of CCND1 was associated with an 8-fold elevated risk of progression compared with those with no gain in time-to-progression analysis. Numerical alterations of EGFR and CCND1 and their centromeres might be an effective means for identifying OPLs at risk. Future studies will expand on this analysis and set the stage for application of this approach in routine clinical practice.
尽管手术切除，口腔癌前病变（OPL）患者亚组仍存在极高的发展为浸润性癌症的风险。本研究的目的是评估特定基因及其相关着丝粒作为标记物，对 OPL 进行癌症风险分层的效用。本研究使用的样本包括 35 例已知结局的口腔发育异常和 20 例正常口腔黏膜。其中 20 例发育异常来自正在进行的纵向研究，显示有进展。其余 15 例（其中 2 例进展）是从基于人群的省级 BC 口腔活检服务（OBS）中选择的。通过荧光原位杂交（FISH）评估 EGFR、CEP7、CCND1 和 CEP11 的拷贝数改变。进展者和非进展者之间在人口统计学方面没有显著差异。这些基因及其相应着丝粒的特定 FISH 图谱与进展相关。与无进展时间分析中无 CCND1 基因获得的患者相比，CCND1 基因获得高表达与进展风险增加 8 倍相关。EGFR 和 CCND1 及其着丝粒的数值改变可能是识别高危 OPL 的有效方法。未来的研究将在此基础上进一步扩展，并为该方法在常规临床实践中的应用奠定基础。
