[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.