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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 3 7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 ,2 2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 2 2 % ,重度不典型增生 (HGD)为 15 %和 3 3 % ,ESCC为 3 5 %和 64 %。LGD与HGD比较有非常显著性差异 (P =0 .0 2 ,P =0 .0 0 1,P =0 .0 0 7) ;HGD与ESCC比较无显著性差异。其中的 10个标志物 (D3S45 45 ,D 5S2 5 0 1,D8S110 6,D 9S1118,D 9S910 ,D13S14 93 ,D 13S894,D 13S796,D15S65 5 ,D 17S13 0 3 )分别在 1例以上的癌前病变中出现等位缺失。结论 LOH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。
Objective To investigate the relationship between early lesions and genetic changes in esophageal squamous cell carcinoma (ESCC) and to screen and evaluate microsatellite markers that may serve as indicators for early diagnosis and early-warning of esophageal cancer. Methods Sixteen isotope-labeled microsatellite markers with high frequency heterozygosity loss (LOH) in invasive esophageal squamous cell carcinoma were selected and analyzed by laser capture microdissection (LCM) to analyze 37 cases of esophageal biopsy. There were genetic changes in the degree of lesions, including 15 cases of dysplasia and 22 cases of ESCC. Results The incidences of LOH frequency and microsatellite instability (MSI) of 16 microsatellite markers were: mild atypical hyperplasia (LGD) was 2% and 22%, and severe dysplasia (HGD) was 15%. 3 3%, ESCC is 35% and 64%. There was a significant difference between LGD and HGD (P = 0.02, P = 0.010, P = 0.007); there was no significant difference between HGD and ESCC. Among them, 10 markers (D3S45 45, D5S2 5 0, D8S110 6, D 9S1118, D 9S910, D13S14 93, D 13S894, D 13S796, D15S65 5, D 17S13 0 3) were more than 1 case of precancerous Alleles are missing in the lesion. Conclusion The frequency of LOH and MSI increased with the histological severity of the lesion, and the allele deletion was higher in the detection of precancerous lesions. The occurrence and progression of esophageal cancer are closely related to genetic instability. This molecular change can be detected by esophagoscopic biopsy. Microsatellite markers may be useful markers for the early diagnosis of esophageal cancer.