高与低风险部位口腔癌前损伤的LOH比较

A Comparison of LOH Pattern of Oral Premalignant Lesions at Low-Risk Sites with Those at High-Risk Sites

目的:检测高、低风险部位的不同程度口腔癌前损伤(轻度、中度、重度不典型增生或原位癌)的3p, 9p,17p染色体臂微卫星DNA杂和性缺失(LOH)频率和模式。方法:用PCR 微卫星分析法检测和比较了65例 高风险部位和50例低风险部位的口腔早期和后期不典型增生组织于3p,9p,17p上的11个微卫星位点的LOH 频率和模式。结果:高风险部位(H)早期不典型增生的LOH频率显著高于低风险部位(L),3p:H=48%,L= 23%(P=0.0340);9p:H=56%,L=23%(P=0.0030);17p:H=33%,L=10%(P=0.0155),1个以上染色体 的LOH结果:H=43%,L=10%(P=0.0010)。高、低风险部位后期不典型增生均表现高频率LOH,无损伤部位 差异,3p:H=52%,L=33%(P=0.4440);9p:H=83%,L=70%(P=0.6456);17p:H=68%,L=80%(P= 0.6808),1个以上染色体的LOH,H=73%,L=67%(P=1.0000)。结论:高风险部位早期不典型增生的LOH 频率的增加可能是恶变风险增加的原因之一;后期不典型增生已经发生了许多足以导致恶变的LOH,以致部位 的差异无统计学意义。研究结果提示用分子生物学方法协同组织病理学标准预测癌前损伤尤其早期不典型增 生的恶变风险更为可靠。

Objective: To explore the frequency and pattern of loss of heterozygosity of microsatellite DNA (LOH) in chromosomal arms of 3p, 9p, and 17p in different degrees of oral premalignant lesions (mild, moderate, and severe dysplasia/CIS) at both low and high-risk sites. Methods: Microdissected archival paraffin tissues of 65 dysplasias from high-risk sites and 50 dysplasias from low-risk sites were examined and compared using a total of 11 microsatellite markers located on chromosome arms: 3p, 9p, and 17p. Results: Early lesions from high-risk sites (H) contained a significantly higher frequency of LOH than those from low-risk sites (L): on 3p, H=48%, L=23% (P<0.05); on 9p, H=56%, L=23% (P<0.01); on 17p, H=33%, L=10% (P<0.05); for allelic loss at more than one arm, H=43%, L=10% (P<0.01). Allelic loss in late lesions showed a similar high frequency of LOH regardless of location. The frequency of loss was as follows: on 3p, H=52%, L=33% (P>0.05); on 9p, H=83%, L=70% (P>0.05); on 17p, H=68%, L=80% (P>0.05); for allelic loss at more than one arm, H=73%, L=67% (P>0.05). Conclusions: The results suggest that the increased allelic loss in early dysplasia from high-risk sites may be partly responsible for its increased malignant risk. But, this difference was not seen in late dysplasia, suggesting that much of the allelic loss required for malignant transformation is already present in such lesions, consistent with the fact that these lesions have a high probability of becoming invasive regardless of site. This study supports the use of molecular methods to assist pathologists in differentiating of premalignant lesions, especially those at low-risk sites, which only infrequently develop to cancer.