Expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) inversely correlates with tumor progression in gastric adenomas and carcinomas.

Abstract

PURPOSE: The expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), one of TGF-beta superfamily gene, is reported to be responsible for NSAID-induced apoptosis. We analyzed NAG-1 expression in gastric cancer and adenoma to find out its clinical implication.

METHODS: Immunostaining was performed using standard procedures with antibody to NAG-1 on gastric tissue microarrays of tissue specimens obtained by gastrectomy. The immunoreactivity of normal and tumor tissues was graded as no, weak, moderate, and strong expression.

RESULTS: The NAG-1 expression was stronger in intestinal metaplasia and adenoma than normal gastric epithelium. 47 (74.6%) of 63 normal gastric epithelium showed no or weak expression, but 33 (56.9%) of 58 and 13 (86.7%) of 15 intestinal metaplsia and adenoma showed moderate or strong expression. Only NAG-1 expression in diffuse type gastric cancer was weaker than in normal gastric tissue. Compared to intestinal metaplasia, both intestinal and diffuse type gastric cancer showed weaker expression. The intensity of NAG-1 expression inversely correlated with tumor differentiation and T and N stage status. While only 1 (2.2%) of 45 T1 stage cases lacked NAG-1 expression, 27 (45.8%) of 59 T3 stage cases lacked NAG-1 expression. Likewise, in N0 stage tumors only 10 (15.4%) of 65 cases lacked NAG-1 expression, but 17 (63.0%) of 27 N3 cases lacked NAG-1 expression.

CONCLUSIONS: The NAG-1 was expressed strongly in intestinal metaplasia and adenoma, and inversely correlated to tumor stages. This interesting finding may provide new targets for chemoprevention and future development of drugs.