Reduced expression of the TSP1 gene and its association with promoter hypermethylation in gastric carcinoma

Thrombospondin-1 (TSP1) is a potent peptide shown in some tumor systems to be linked with angiogenesis. Epigenetic alteration of TSP1 has been reported in various primary tumors. However, the expression pattern of TSP1 has not been characterized in gastric carcinoma. We measured levels of TSP1 mRNA expression using quantitative RT-PCR in 30 gastric carcinomas and 10 nonneoplastic mucosae. In addition, we examined the correlation of the levels of TSP1 mRNA expression levels with promoter methylation status of TSP1 monitored by methylation-specific PCR as well as p53 mutation status detected by PCR-single-strand conformation polymorphism. Promoter hypermethylation of the TSP1 gene was found in 10 (33%) of 30 gastric carcinomas, and TSP1 mRNA expression levels were associated with promoter hypermethylation of TSP1 (p = 0.017; Mann-Whitney U test). p53 mutation was found in 5 (17%) of 30 gastric carcinomas, however, TSP1 mRNA expression was not associated with p53 mutation status (p = 0.858; Mann-Whitney U test). There was no correlation between TSP1 mRNA expression levels and T grade, N grade, tumor stage, or histological type. Our results suggest that transcriptional inactivation of TSP1 by aberrant DNA methylation of the promoter region may participate partly in stomach carcinogenesis through TSP1 downregulation.