Expression of inducible nitric oxide synthase and cyclooxygenase-2 in angiogenesis and clinical outcome of human gastric cancer

Abstract

It has been recognized that inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) produce important endogenous factors of human tumors such as nitric oxide (NO) and prostaglandins, which is involved in the process of carcinogenesis and tumor progression. This study aimed to evaluate the association of clinicopathologic factors, microvessel density, and patient survival with the expression of iNOS and COX-2 in patients with gastric adenocarcinoma. Seventy-nine specimens, resected from patients with gastric adenocarcinoma, were investigated by immunohistochemical stain against iNOS and COX-2. Microvessels were stained using anti-CD34 antibody and counted as microvessel density. Positive iNOS and COX-2 expressions were significantly correlated with microvessel density by multivariate analysis, respectively (P = 0.0127 vs. P = 0.0214). There was significant difference among the four groups (both iNOS and COX-2 positive, iNOS positive only, COX-2 positive only, and both negative) in serosal invasion (P = 0.038), lymph node metastasis (P = 0.038), Helicobacter pylori infection (P = 0.025), vascular invasion (P = 0.035), and microvessel density (P = 0.019). In patients with gastric cancer that co-expressed iNOS and COX-2, prognosis was significantly poorer than in those that expressed either iNOS or COX-2, or did not express both of them (P = 0.01738). The Cox proportional hazard regression analysis indicated that iNOS expression, vascular invasion, serosal invasion, and microvessel density are independent prognostic factors for patients with gastric cancer. iNOS and COX-2 expression of gastric cancer are related to tumor angiogenesis, tumor progression, and patient survival in human gastric cancer.