Expression of COX‐2, mPGE‐synthase 1 , MDR‐1 (P‐gp), and Bcl‐x L : a molecular pathway of H pylori ‐related gastric carcinogenesis

• Published in: The Journal of pathology Vol. 202; no. 3; pp. 305 - 312
• Main Authors: Nardone, Gerardo, Rocco, Alba, Vaira, Dino, Staibano, Stefania, Budillon, Alfredo, Tatangelo, Fabiana, Sciulli, Maria G., Perna, Federico, Salvatore, Gaetano, Di Benedetto, Maria, De Rosa, Gaetano, Patrignani, Paola
• Format: Journal Article
• Language: English
• Published: 01.03.2004
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.1512

Abstract Helicobacter pylori up‐regulates cyclo‐oxygenase‐2 (COX‐2) expression, which in turn is involved in tumourigenesis. Recently, a causal link between COX‐2 and multidrug resistance 1 ( MDR‐1 ) gene expression, implicated in cancer chemoresistance, has been demonstrated. Thus, the expression of COX‐2 and the downstream enzyme involved in PGE 2 biosynthesis, microsomal PGE‐synthase 1 (mPGES 1 ), was correlated with P‐gp, the product of MDR‐1 , and the anti‐apoptotic protein, Bcl‐x L , in gastric biopsies from patients with H pylori infection and in patients with gastric cancer. In a retrospective analysis of endoscopic and pathology files, 40 H pylori ‐negative patients ( Hp −), 50 H pylori ‐positive patients who responded to eradication therapy ( Hp +R), 84 H pylori ‐positive patients who did not respond to eradication therapy ( Hp +NR), and 30 patients with gastric cancer (18 intestinal and 12 diffuse types) were selected. COX‐2, mPGES 1 , P‐gp, and Bcl‐x L were detected by immunohistochemistry. COX‐2, mPGES 1 , P‐gp, and Bcl‐x L expression was undetectable in gastric mucosa from Hp − patients. By contrast, COX‐2 and mPGES 1 expression was detected in 42% and 44% of Hp +R patients, respectively, and in up to 66% (range 63–66%) of Hp +NR patients ( p < 0.05). The expression of COX‐2 and mPGES 1 correlated significantly ( p < 0.0001) with that of P‐gp and Bcl‐x L . High levels of COX‐2, mPGES 1 , P‐gp, and Bcl‐x L expression were found in intestinal‐type gastric cancer samples. In conclusion, H pylori ‐dependent induction of COX‐2 and mPGES 1 is associated with enhanced production of P‐gp and Bcl‐x L that may contribute to gastric tumourigenesis and resistance to therapy. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.