Promoter methylation of several tumor suppressor genes in human gastric adenocarcinoma

Abstract

To study the promoter methylation of several tumor suppressor genes in human gastric foveolar epithelia (GFE) of chronic gastritis, adjacent GFE of gastric adenocarcinoma (GAC) and GAC. Methylation specific PCR (MSP) technique was used to examine the promoter methylation of 4 tumor suppressor genes (E-cadherin, hMLH1, APC, and MGMT) in 106 paraffin-embedded specimens of GAC, including tumor tissues and adjacent GFE, and 16 paraffin-embedded specimens of GFE of chronic gastritis. Immunohistochemistry was used to detect the protein expression of E-cadherin (E-CD) in 46 out of the 106 cases of GAC. The promoter methylation rates of tumor suppressor genes in the GAC tissue were 72.6% (77/106), significantly higher than that in the adjacent GFE (44.3%, 47/106) and the GFE of chronic gastritis (12.5%, 2/16, P < 0.01). The promote methylation rate of tumor suppressor genes in the GAC Laurén diffuse type was 80.6% (50/62), significantly higher than that of the GAC of intestinal type (61.4%, 27/44, P < 0.01). The rates of promoter methylation was significantly associated with depth of penetration, pTNM staging and degree of differentiation in GAC (all P < 0.05), but was no significantly associated with age, gender, Ming's classification and local lymph node metastasis (all P > 0.05). The rate of loss of E-CD protein expression or heterogeneously reduction of E-CD protein expression in the specimens of GAC with promoter methylation was 90.9% (20/22), significantly higher than that in the specimens of GAC without promoter methylation (9/24, 37.5%, P < 0.01). Promoter methylation of above tumor suppressor genes is seldom found in the GFE of chronic gastritis, frequently found in the adjacent GFE of GAC, but very commonly in GAC. Promoter methylation may be an early event in the carcinogenesis of GAC. E-CD gene promoter methylation is closely related to loss or heterogeneously reduction of E-CD protein expression.