食管鳞癌及癌前病变活检组织的微卫星改变

目的 探讨食管鳞状细胞癌（ESCC）早期病变与遗传学改变之间的关系，筛选和评价可能作为食管癌早期诊断预警指标的微卫星标志物。方法 选用曾被证实在浸润性食管鳞癌表现高频率杂合性缺失（LOH）的16个同位素标记微卫星标志物，应用激光捕获显微切割技术（LCM）分析37例食管镜活检组织不同程度病变存在的遗传学改变，包括15例不典型增生，22例ES-CC。结果 16个微卫星标志物LOH频率和微卫星不稳定性（MSI）发生率分别为：轻度不典型增生（LGD）为2%和22%，重度不典型增生（HGD）为15%和33%，ESCC为35%和64%，LGD与HGD比较有非常显著性差异（P=0.02,P=0.001,P=0.007)；HGD与ESCC比较无显著性差异。其中的10个标志物（D3S4545，D5S2501，D8S1106，D9S1118，D9S910，D13S1493，D13S894，D13S796，D15S655，D17S1303）分别在1例以上的癌前病变中出现等位缺失。结论 LDH和MSI的发生频率均随病变的组织学严重程度而增高，且等位缺失在食管癌前病变检出率较高，食管癌的发生和进展与基因不稳定性密切相关，这种分子改变能够通过食管镜活检组织检测。微卫星标志物可能成为食管癌早期诊断的有用标志物。

Microsatellite Alterations in Esophageal Precursor Lesion and Squamous Cell Carcinoma from Endoscopic Biopsies

Objective To evaluate the relationship between the early esophageal cancer and precursor lesions with genetics changes,and to look for potential early detection microsatellite markers.Methods By means of Laser capture micro dissection(LCM),16 polymorphic radio labeled microsatellite markers were selected to represent the marker loci identified as having the highest frequencies of loss of heterozygosity(LOH) in invasive ESCC,37 cases,including 15 dysplasia of the esophagus and 22 invasive ESCC,were studie.Results Allelic loss was seen in 2% of the markers in patients with low grade dysplasia(LGD),15% with high grade dysplasia(HGD),and 35% with ESCC.The difference between LGD vs HGD vs ESCC,and HGD vs ESCC were all statistically significant( P =0.02, P =0.001, P =0.007);The frequency of microsatellite instability(MSI) was 22% for LGD,33% for HGD,and 64% for ESCC,but no statistically difference was shown.Ten different markers(D3S4545,D5S2501,D8S1106,D9S1118,D9S910,D13S1493,D13S894,D13S796,D15S655 and D17S1303) showed allelic loss in one or more of the premalignant lesions tested.Conclusion The total frequency of allelic loss and microsatellite instability both increase with increasing histomorphologic disease severity,and allelic loss is common in premaligment lesions.Our findings indicate that the development of ESCC is associated with genetic instability that can be detected in endoscopic biopsies of recognized precursor lesions.The instability may be a basis for future screening as early detection markers and likely will be useful in the early predisposition for ESCC.