COX-2, VEGF expression in gastric carcinoma and metastatic lymph nodes and their relation with angiogenesis

Purpose:Cyclooxygenase is a key enzyme in prostaglandin biosynthesis. COX-2 is induced by mitogens, cytokines and growth factors and is primarily responsible for prostaglandins produced in inflammatory sites. Recent studies have demonstrated that COX-2 could affect carcinogenesis via several different mechanisms, including cell proliferation, apoptosis, modulation of the immune system, angiogenesis and adhesion to the extracellular matrix.VEGF, the most well-characterized potent angiogenic-mitogenic factor for endothelial cells which is closely associated with neovascularization in cancers. The expression of VEGF is shown to be induced by hypoxia, growth factors, mutation of tumor supressor genes and decrease in pH. VEGF has been regarded as a general endothelial growth factor acting on all processes of angiogenesis such as extravasation, proliferation, migration, tube formation and differantion of endothelial cells. High levels of expression of VEGF and their receptors are found in many solid tumors including breast, colon, ovary, cervix, kidney, gastric and non-small cell lung carcinoma VEGF expression in cancers are associated with poor prognosis.In recent years, it is found out that angiogenesis is also an important prognostic indicator for gastric carcinoma. Angiogenesis is a basic process in reproduction, development and repair. Physiologic angiogenesis is kept under control strictly. Pathologic angiogenesis seen in neoplastic cases is the constant growth of blood vessels, that is, uncontrolled neovascularization. Microvessel density (MVD) is regarded as a surrogate marker for angiogenesis and has been used for tumor prognosis.Material and Methods:In this study, COX-2, VEGF expression and MVD grade that was identified by antibodies against CD34 were investigated immunohistochemically in 33 patients with gastric carcinoma. Their relation with clinicopathological parameters and prognosis were determined.Results:The expression of COX-2 protein was %96,9 in normal mucosa and %87,8 in gastric carcinoma. Although COX-2 expression in mucosa was higher than in carcinoma, the difference was not statistically significant. The COX-2 positivity rates in the lymph nodes were significantly higher in patients with vascular invasion (p<0,01).The expression of VEGF protein was %100 in normal mucosa and %93,9 in gastric carcinoma. VEGF levels in normal mucosa were significantly higher than in carcinoma (p=0,05).The results of CD34 staining were similar. MVD grade in mucosa was significantly higher than in gastric carcinoma (p<0,01). MVD values were significantly higher in poorly differentiated carcinomas carcinoma than in well differentiated and moderately differentiated carcinoma (p<0,05).There was no association between COX-2, VEGF expression and MVD grade. There was no correlation between COX-2, VEGF, CD34 expression (MVD grade) and clinicopathological parameters such as age, tumor dimension, grade, lymph node metastasis, depth of invasion, vascular invasion and alterations of adjacent mucosa. Also no significant relation was detected between COX-2, VEGF expression and MVD grade in metastatic lymph nodes.Conclusion:Our results suggest that the density of microvessels in gastric carcinoma may correlate with tumour grade, but the precise roles of COX-2 and VEGF in gastric cancers is not yet fully understood. Futher studies with large case series are needed to clarify importance of COX-2, VEGF and MVD in progress of cancers and their relation with each other.