Clinical significance of urinary vascular endothelial growth factor and microvessel density in patients with renal cell carcinoma

Objectives. To investigate the urinary vascular endothelial growth factor (VEGF) levels from patients with renal cell carcinoma (RCC). Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. VEGF is thought to exert potent angiogenic activity. Methods. Urine samples were obtained before radical nephrectomy from 27 patients with RCC and 10 control subjects with no evidence of cancer or inflammatory disease. VEGF was measured by enzyme-linked immunosorbent assay in the urine and corrected according to the 24-hour urine concentration of creatinine. The microvessel density was measured by immunohistochemical staining with CD31 monoclonal antibody. Nuclear morphometry was performed by photomicroscopy. Results. The corrected urinary VEGF levels in patients with RCC were much higher than those in the normal control group ( P = 0.039) and were more elevated in patients with higher stages of RCC (Stages III and IV versus Stages I and II; P = 0.024). A tendency was also noted for the VEGF levels to be higher according to cell grade. However, no statistical correlation was found between the corrected urinary VEGF and age, sex, tumor size, cell type, microvessel density, platelet count, or hemoglobin. The nuclear area was higher with more advanced-stage tumors ( P = 0.043) and tended to increase according to the tumor cell grade. Conclusions. The results of this study indicate that urinary VEGF levels are increased in patients with RCC. However, they may not reflect the underlying angiogenic activity, and it may be that other angiogenic factors play a more prominent role.