Cyclooxygenase-2 Expression in Helicobacter pylori-Associated Premalignant and Malignant Gastric Lesions

Abstract

Expression of cyclooxygenase-2 (COX-2) in various stages of the Helicobacter pylori-associated gastric carcinogenesis pathway has not been elucidated. We investigated the distribution and intensity of COX-2 expression in premalignant and malignant gastric lesions, and monitored the changes after H. pylori eradication. Gastric biopsies from H. pylori-infected patients with chronic active gastritis, gastric atrophy, intestinal metaplasia (IM), gastric adenocarcinoma, and noninfected controls were studied. Expression of COX-2 was evaluated by immunohistochemistry and in situ hybridization. Endoscopic biopsies were repeated 1 year after successful eradication of H. pylori in a group of IM patients for comparing COX-2 expression and progression of IM. In all H. pylori-infected patients, COX-2 expression was predominantly found in the foveolar and glandular epithelium and, to a lesser extent, in the lamina propria. In the noninfected group, only 35% of cases demonstrated weak COX-2 expression. Intensity of COX-2 was not significantly different between the chronic active gastritis, gastric atrophy, IM, and gastric adenocarcinoma groups. In 17 patients with IM, COX-2 expressions in the epithelial cells and stromal cells were reduced 1 year after H. pylori eradication. However, the changes in COX-2 expression did not correlate with progression/regression of IM. Both premalignant and malignant gastric lesions demonstrate strong COX-2 expression. Successful eradication of H. pylori leads to down-regulation of COX-2 expression but failed to reverse IM at 1 year.

Increased expression of survivin in gastric cancer patients and in first degree relatives

“…While p53 and bcl-2 are involved in the modulation of cell progression and viability, the role of other mediators of apoptosis has not been examined yet. Previously, we have demonstrated COX-2 up-regulation in gastric cancer and pre-neoplastic gastric lesions that may play contribute to the carcinogenesis process (Sung et al, 2000;Leung et al, 2001). Overexpression of COX-2 in intestinal epithelial cells results in inhibition of apoptosis (Tsujii and DuBois, 1995), which is similar to the action of survivin.…”

“…Increased cyclo-oxygenase-2 (COX-2) expression has been demonstrated in the process of gastric carcinogenesis (Ristimaki et al, 1997;Sung et al, 2000;Leung et al, 2001). Considerable evidence suggests that the increase in tumorigenic potential of COX-2 expressing cells is related to the resistance to apoptosis (Tsujii and DuBois, 1995).…”

NF-κB signaling, liver disease and hepatoprotective agents

“…NO generated by iNOS is converted to reactive nitrogen species, which can exert oncogenic effects including direct DNA damage, oncogenic mutations, inhibition of apoptosis and may also promote angiogenesis (Jaiswal et al, 2001). H. pylori infection is also known to induce the expression of the proinflammatory cyclooxygenase 2 (COX-2) enzyme (Salvemini et al, 1993;Ristimaki et al, 1997;Sung et al, 2000). COX-2 expression is usually undetectable in most normal tissues, but is induced rapidly during an inflammatory reaction (Smith et al, 1996;Turini and DuBois, 2002).…”

Wnt signaling and gastrointestinal tumorigenesis in mouse models

“…Based on such an 'indirect' mechanism hypothesis, we have focused on the role of prostaglandin (PG) E 2 in earlier stages of gastric carcinogenesis. It is known that Helicobacter infection induces COX-2 and microsomal prostaglandin E synthase (mPGES)-1 in the gastric mucosa (Sung et al, 2000;Oshima et al, 2004). COX-2 is induced also in gastric cancer tissues (Ristimaki et al, 1997).…”