Expression of nuclear factor-kappa B and target genes in gastric precancerous lesions and adenocarcinoma: Association with Helicobactor pylori cagA (+) infection

摘要

AIM: To examine the expression of nuclear factor kappaB (NF-κB) and its target genes in intestinal metaplasia (IM), dysplasia (DYS) and gastric carcinoma (GC) infected with Helicobacter pylori (H pylori) and to investigate the mechanism underlying H pylori cytotoxin associated gene A (cag A) infection leading to gastric adenocarcinoma. METHODS: Expressions of NF-κB/p65 and its target genes: c-myc, cyclinDl and bcl-xl were immunohistochemically examined in 289 cases of gastric biopsy and resection specimens from patients with IM, DYS and GC infected with H pylori. H pylori in the above mentioned tissues was detected by Warthin-Starry stain and rapid urease tests. IgG antibody to cagA in sera of the patients was measured by ELISA. RESULTS: The positive rates of NF-κB/p65 were significantly higher in groups with cagA of IMI-Ⅱ(28/33), IM Ⅲ(48/52), DYSI(27/31), DYS Ⅱ-Ⅲ(28/32), GC(35/40) than in groups without cagA of IMI-Ⅱ(4/17), IMIⅡ(3/20), DYSI(3/20), DYSⅡ-Ⅲ(6/21), GC(10/23). The expressions of c-myc, cyclinD1, and bcl-xl were significantly higher in groups with cagA of IM Ⅲ(47/52, 49/52, 46/52), DYSII-Ⅲ(29/32, 26/32, 25/32) than in groups without cagA of IM Ⅲ(8/20, 7/20, 5/20), DYSII-Ⅲ(10/21, 8/21, 3/21), which were in conformity with the expression of NF-κB in IM Ⅲ, and DYSII-Ⅲ. A significantly higher expression level of NF-κB/p65, c-myc, cyclinD1 and bcl-xl was detected in intestinal type GC(27/28, 18/28, 22/28, 24/28) than in diffuse type GC(8/12, 3/12, 3/12, 6/12), respectively. CONCLUSION: There may be two different molecular mechanisms in the occurrence of intestinal and diffuse type gastric carcinomas. Intestinal type gastric carcinoma is strongly associated with high expression of c-myc, cyclinD1 and bcl-xl through NF-κB/p65 activated by H pylori cagA. Inhibiting the activity of NF-KB is an effective and promising way to prevent intestinal type gastric carcinoma.