SUMMARY
Introduction: The aims of this study were to investigate theimmunohistochemical expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor-C (VEGF-C), theircorrelation with lymphangiogenesis, angiogenesis and clinicopathologicalsignificance in human gastric cancer.Material and methods: Tissue samples of gastric cancer of 60patients, who underwent Billroth II resection, were analyzed.The expression of COX-2 and VEGF-C proteins was calculatedusing a semi-quantitative immunoreactive score method.Quantitative analysis of lymphangiogenesis and angiogenesiswas performed according to the method described by Weidner.Lymphangiogenesis was evaluated by immunostaining withD2-40. Angiogenesis was assessed by CD105 immunostaining.Results: There was a statistically significant difference in themean values of COX-2 (p< 0.01) and VEGF-C (p< 0.05) betweengastric cancer samples and in control samples. Angiogenesiswas significantly higher in neoplastic tissue then in control group(p<0.001). Expression of COX-2 showed a significant positivelinear correlation with angiogenesis (p<0.05). However, COX-2did not correlate with VEGF-C or lymphangiogenesis. There wasan association between VEGF-C and lymphangiogenesis, butwithout statistical significance. Lymphangiogenesis significantlycorrelated with lymph node metastasis (p=0.007). Expression ofCOX-2 showed significant correlation with type of Bormann’sclassification (p=0.019) and depth of invasion (p=0.03).Conclusions: The tumor cells are the major source of COX-2and VEGF-C in gastric carcinomas. Their correlation did notshow that COX-2 overexpression promotes tumor lymphangiogenesisthrough augmentation of VEGF-C. The results of thisstudy suggest that neoangiogenesis is a dominant process duringtumor progression, whereas lymphangiogenesis plays an importantrole in lymph node metastasis.Keywords: angiogenesis, CD105, COX-2, D2-40, gastric cancer,lymphangiogenesis, VEGF-C