[Loss of heterozygosity analysis of microsatellites on multiple chromosome regions in dysplasia 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 microsatellites 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 heterozygosity 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.

[Study on human papillomavirus infection and loss of heterozygosity of microsatellite in esophageal cancer].

OBJECTIVE: To investigate the relationship between the loss of heterozygosity(LOH) at 14 microsatellites in esophageal cancer and human papillomavirus (HPV) infection. METHODS: HPV-16,18 DNA was examined in 112 tumor specimens using fluorescence quantitative PCR. 112 tumor specimens and their matched blood DNAs were analyzed for LOH at 14 microsatellites by PCR and fluorescence-based DNA sequencing technology. The frequencies of LOH at 14 microsatellites were compared between HPV positive and negative specimens. RESULTS: High frequency of LOH was observed among chromosome arms 3p, 9p, 13q, 17p and 17q. The frequency of LOH was significantly higher at loci D13S260 and D6S497 in HPV positive specimens, comparing with HPV negative ones. CONCLUSION: The findings regarding loci with allele loss indicated that widespread chromosome instability might have existed in esophageal cancer. HPV positive specimens with higher frequency of LOH than negative ones at locus D13S260 and D6S497 suggesting that the target of HPV in esophageal cancer might serve as candidate genes at these two loci. In addition,this result also indicated that HPV might be a high-risk factor for esophageal cancer in Sichuan area with a high incidence of this cancer.