Vascular endothelial growth factor (VEGF) is the most potent angiogenic pro
tein known, and is elevated in serum of colorectal cancer patients. We unde
rtook four studies to determine the efficacy of pre-operative serum VEGF as
a staging tool and a predictor of curative resection, recurrence and outco
me in colorectal cancer. Serum VEGF was assayed by quantitative ELISA. One-
hundred eight patients with colorectal cancer and 136 normal control were r
ecruited. ANOVA demonstrated a significant difference between the Dukes sta
ges (P=0.007), T stages (P=0.001) and Union Internationale Contre Le Cancer
(UICC) stages (P=0.001). In metastatic and node-positive disease, pre-oper
ative serum VEGF was elevated compared with metastatic-free (P=0.03) and: n
ode-negative disease (P=0.008) and controls (P<0.0005). Ninety-four patient
s undergoing colonic resections (67 curative, 15 palliative and 12 benign)
were recruited. Curative resections had a significant fall in post-operativ
e VEGF levels compared with preoperative serum VEGF (P<0.0005). There was n
o fall in palliative (P=0.32) and benign (P=0.28) groups. Ninety-one patien
ts who had undergone curative resections were recruited. Using multivariate
logistic: regression analysis, pre-operative serum VEGF was the most impor
tant prognostic factor regardless of nodal status and adjuvant chemotherapy
, and was superior to nodal status in predicting outcome (P=0.0001). During
follow-up of 79 patients after curative resections, serum VEGF was equally
distributed in disease free patients regardless of their Dukes' stage. Lev
els of serum VEGF above 347 pg/mL (mean + 2 SD of normal control) accuratel
y detected the metastases (P<0.0001) with sensitivity of 79% and specificit
y of 80%. These studies lead us to conclude that pre-operative serum VEGF h
as the potential to be used as a diagnostic tool for disease stages, to pre
dict oncological clearance of colorectal resection, and is a powerful predi
ctor of outcome and disease recurrence. These data support the use of pre-o
perative serum VEGF as a potential tumor marker in colorectal cancer.