Vascular endothelial growth factor and soluble Tie-2 receptor in colorectal cancer: associations with disease recurrence.

Aims: A delicate balance exists between pro-angiogenic factors and anti-angiogenic factors to regulate the process of angiogenesis. To investigate the relationship of VEGF-A with other angiogenic factors and to determine their clinical usefulness.

Methods: Venous blood was obtained from 47 patients with CRC prior to curative resections. VEGF-A, sVEGFR-1, sTie-2 receptor, and TNF-alpha levels in serum were measured concurrently with quantitative ELISA. The median follow-up term for patients without cancer death was 29 months (range 20-35).

Results: Both serum TNF-alpha activity and sVEGFR-1 was detectable in 17% and 74% of CRC patients, respectively. Univariate analysis demonstrated that the disease free survival was significantly associated with the tumour location (P=0.031), T category (P=0.006), TNF-alpha activity (P=0.0008), sTie-2 receptor (P=0.012) and VEGF-A (P<0.00001). From the survival analysis, a higher serum VEGF-A and sTie-2 receptor level is associated with an earlier development of metastases. Using multivariate Cox's regression analysis, the only independent predictors of outcome were sTie-2 receptor (P=0.038) and VEGF-A (P=0.006).

Conclusions: sTie-2 receptor and VEGF-A appear to associate independently with the development of metastases, with VEGF-A being the most powerful predictor of outcome. These data also suggest that measurement of pre-operative sTie-2 receptor and VEGF-A is superior to determining VEGF-A alone with regards to predictive value.