Cyclooxygenase-2 Expression Is Associated with Vascular Endothelial Growth Factor-C and Lymph Node Metastases in Human Prostate Cancer

Abstract

Recent observations suggest an implication of cyclooxygenase-2 (COX-2) in tumor lymphangiogenesis through an upregulation of vascular endothelial growth factor-C (VEGF-C) expression. However, it is unclear whether COX-2 is also associated with VEGF-C expression, tumor lymphangiogenesis and lymph node metastasis in human prostate cancer. COX-2 and VEGF-C expression were examined in tumor tissues from 58 prostate cancer patients using immunohistochemical staining. We also analyzed the association of COX-2 and VEGF-C expression with tumor lymphangiogenesis quantified as lymphatic vessel density (LVD), lymph node metastasis, and patients' biochemical progression-free survival (b-PFS). High expression of either COX-2 or VEGF-C was correlated with tumor lymphangiogenesis and lymph node metastasis, as well as poor b-PFS. Moreover, a strong correlation was found between expression of COX-2 and VEGF-C (r = 0.631, p <0.001). COX-2 is positively associated with VEGF-C expression, tumor lymphangiogenesis and lymphatic metastasis in prostate cancer. These findings suggest that COX-2 may play a pivotal role in lymphangiogenesis and lymph node metastasis of prostate cancer via the regulation of VEGF-C expression.