The expression of COX-2 and VEGF-C in gastric cancer: correlation with lymphangiogenesis, angiogenesis and clinicopathological parameters
Introduction: The aims of this study were to investigate the immunohistochemical expression of cyclooxygenase-2 (COX- 2) and vascular endothelial growth factor-C (VEGF-C), their correlation with lymphangiogenesis, angiogenesis and clinicopathological significance in human gastric cancer. Material and methods: Tissue samples of gastric cancer of 60 patients, who underwent Billroth II resection, were analyzed. The expression of COX-2 and VEGF-C proteins was calculated using a semi-quantitative immunoreactive score method. Quantitative analysis of lymphangiogenesis and angiogenesis was performed according to the method described by Weidner. Lymphangiogenesis was evaluated by immunostaining with D2-40. Angiogenesis was assessed by CD105 immunostaining. Results: There was a statistically significant difference in the mean values of COX-2 (p< 0.01) and VEGF-C (p< 0.05) between gastric cancer samples and in control samples. Angiogenesis was significantly higher in neoplastic tissue then in control group (p<0.001). Expression of COX-2 showed a significant positive linear correlation with angiogenesis (p<0.05). However, COX-2 did not correlate with VEGF-C or lymphangiogenesis. There was an association between VEGF-C and lymphangiogenesis, but without statistical significance. Lymphangiogenesis significantly correlated with lymph node metastasis (p=0.007). Expression of COX-2 showed significant correlation with type of Bormann’s classification (p=0.019) and depth of invasion (p=0.03). Conclusions: The tumor cells are the major source of COX-2 and VEGF-C in gastric carcinomas. Their correlation did not show that COX-2 overexpression promotes tumor lymphangiogenesis through augmentation of VEGF-C. The results of this study suggest that neoangiogenesis is a dominant process during tumor progression, whereas lymphangiogenesis plays an important role in lymph node metastasis. Keywords: angiogenesis, CD105, COX-2, D2-40, gastric cancer, lymphangiogenesis, VEGF-C