Immunohistochemical expression of the cyclooxygenase-2 (COX-2) in gastric cancer. The correlations with the tumor angiogenesis and patients' survival.

INTRODUCTION: The mechanisms by which COX-2 contributes to the carcinogenesis are not known until present. It seems that the COX-2 enzyme stimulates the cell proliferation, inhibits the apoptosis, increases the malignant cells' invasiveness and induces the angiogenesis by elaborating some angiogenic factors.

MATERIAL AND METHODS: In the present study, we intend to evaluate the immunohistochemical expression of COX-2 in gastric carcinomas, keeping track of the correlations between the clinicopathologic factors, the tumor angiogenesis (evaluated by microvascular density--MVD--determination and by VEGF expression) and the patients' survival. In addition, we have tracked the immunoreactions' positivation in the peritumoral mucosa with various lesions, with the purpose to establish the contribution of COX-2 to the gastric carcinogenesis during the pre-invasive stages. A prospective study was realized, regarding the evolution and aggressiveness of the gastric cancer, with a duration of five years, 61 patients operated of gastric cancer being included.

RESULTS: The COX-2 immunoreactions have been significantly more frequent noticed in the gastric carcinomas included in the study (57.4%) and in the epithelial dysplasia areas adjacent to the carcinomas of intestinal type (35.5% of the cases), than in the normal peritumoral mucosa (4.9%) (p<0.001 ES). The COX-2 immunoreactions have turned positive more frequently in gastric carcinomas of intestinal type (68.4%), in comparison to the carcinomas of diffuse type (29.4%) (p<0.001 ES). The COX-2 expression is significantly correlated with the invasion level, the presence of the metastases in the regional lymph nodes and the pTNM stage, but without influencing the prognosis of the gastric cancer patients. The negative VEGF carcinomas have turned positive for COX-2 only for 19% of the cases. Different from those, the positive VEGF carcinomas have associated COX-2 immunoreactivity in 77.5% of the cases.

CONCLUSIONS: The results obtained are suggestive for the predominant expression of COX-2 in the carcinomas of intestinal type and its precursory lesions. Our results show a tight correlation between the immunohistochemical expressions of COX-2 and VEGF in gastric carcinomas (r = 0.562, p < 0.001 ES) and also a MVD average value significantly higher in the positive COX-2 carcinomas, suggesting an intense angiogenesis activity in that group of tumors (p < 0.001 ES).