食管鳞状细胞癌及癌前病变组织中多个染色体区域微卫星杂合性缺失的研究

目的 探讨与食管癌早期癌变的发生、发展密切相关的分子变化,寻找早期诊断的分子标记.方法 采用PCR荧光测序仪凝胶电泳分别检测34例食管癌患者手术切除的鳞状细胞癌(SCC)组织、癌前病变组织及匹配的外周血样本中16个微卫星位标的杂合性缺失状况.将轻、中度不典型增生定义为低级别不典型增生(LGD),将重度不典型增生归为高级别不典型增生(HGD).比较不同病理形态组织中16个位标的杂合缺失率.结果 16个位标的总体缺失率随组织形态的严重程度而升高,LGD中缺失率(9.8%)低于HGD(48.6%)和SCC(58.5%,P＜0.01).有8个位标,即D3S1597、D3S2452、D3S1285、D4S174、D5S2501、D9S125、D13S153和D17S786,在LGD中已呈现杂合性缺失;另发现4例患者的HGD和SCC样本分别在D3S2452、D4S174、D9S125及D17S261处出现了杂合性缺失的逆转.结论 食管鳞状上皮从不典型增生至癌变的过程中需要一系列分子变化的积累;针对某些位标的杂合性缺失分析将有助于食管癌的早期诊断;食管癌的发生可能存在遗传异质性.

Loss of heterozygosity analysis of microsatellites on multiple chromosome regions in dysplasla and squamous cell carcinoma of esophagus

Objective To investigate the molecular alterations related to the carcinogenesis of esophageal squamous cell carcinoma (SCC), and also to find some molecular markers for the early detection of this cancer.Methods The resected tumor specimens and dysplasia tissues from 34 patients with esophageal cancer as well as their matched blood DNAs were analyzed for loss of heterozygosity (LOH) at 16 micresatcilites by using PCR and fluorescence-based DNA sequencing technology. Mild and moderate dysplasia was classified as light-grade dysplasia (LGD), and severe dysplasia as high-grade dysplasia (HGD).The frequencies of LOH at 16 microsatellites were compared between tissue specimens with different histological diagnosis.Results The total frequency of LOH for 16 microsatellites increased significantly in more severe lesions.There was significant difference in the frequency of LOH among LGD and HGD as well as SCC.A total of eight loci (D3S1597, D3S2452, D3S1285, D4S174, D5S2501,D9S125, D13S153 and D17S786) presented LOH in LGD samples.A reversion from LOH to retain of hetorozygosity was observed at loci D3S2452, D4S174, D9S125 and D17S261 respectively when compared HGD with SCC samples obtained from 4 patients.Conclusions An accumulation of molecular alterations would be needed during the carcinogenesis of esophageal cancer.LOH analysis at some specific loci would be helpful for the early detection of esophageal cancer.The genetic heterogeneity possibly exists in the tumorigenesis of esophageal cancer.