Expression of Cyclooxygenase-2 (COX-2) in Helicobacter Pylori Premalignant and Malignant Gastric Lesion, the Association with Tumor Angiogenesis.

Abstract

AbstractBackground: Cyclooxygenase-2 (Cox-2) is a central mediator in inflammation and cancer. Expression of the Cox-2 gene is up-regulated in the gastric mucosa during H. pylori infection.Vascular endothelial growth factor (VEGF) has a potent angiogenic activity and cyclooxygenase-2 (COX-2) promotes angiogenesis by modulated production of angiogenic factors including VEGF.Aim: investigate the distribution and intensity of COX-2 and VEGF expression in premalignant and malignant gastric lesions with H. pylori.Material and Methods: Gastric biopsies from patients with chronic active gastritis and gastric adenocarcinoma, and control group were studied. Immunohistochemical analysis was used to examine the expression of COX-2 and VEGF in 81 cases of patients, including 30 cases with chronic gastritis infected with H. pylori, 51 cases of gastric cancer, 42 cases from GC have H. pylori and 30 cases with normal mucosa and none infected with H. pylori as control group.Results: In H. pylori-infected patients, COX-2 expression was predominantly found in the epithelium and, to a lesser extent, in the lamina propria. In the non infected group, few cases demonstrated weak COX-2 expression. Intensity of COX-2 was significantly different between the chronic active gastritis, gastric adenocarcinoma groups and control group. The positive rate of COX-2 was increased from chronic gastritis (60%), to gastric cancer (88.09%) in patients with H. pylori, compared with negative ones (22.58%). COX-2 was expressed in 23 of 24 intestinal types and in 14 of 18 diffuse types' carcinomas. The negative VEGF carcinomas have turned positive for COX-2 only for 76.92% of the cases. Different from those, the positive VEGF carcinomas have associated COX-2 immunoreactivity in 93.10% of the cases. Conclusions: These results suggest that COX-2 may play an important role in carcinogenesis by stimulating tumor angiogenesis. Also, show a relation between the expressions of COX-2 and VEGF in gastric carcinomas and the value significantly higher in the positive COX-2 carcinomas, suggesting an intense angiogenesis activity in that group of tumors.Keywords: Gastric cancer, Cox-2, H. pylori, tumor angiogenesis, VEGF