Vascular Endothelial Growth Factor-A Expression Is Associated with Subsequent Recurrence in the Liver During Long-Term Follow-Up of Colorectal Cancer Patients in Dukes C

Background We aimed to determine the subgroup of patients with colorectal cancer, in which expression of vascular endothelial growth factor-A (VEGF-A) affects their prognosis strongly. Methods 119 paraffin embedded specimens of colorectal cancer were investigated by staining with a monoclonal antibody against VEGF-A as well as basic fibroblast growth factor (FGF2), CD34 and p53, which was compared with the pattern of liver metastasis or recurrence and overall survival. Results VEGF-A positive ratio was higher in patients with liver metastasis at diagnosis (45% of 46) or recurrence in the liver during follow-up (39% of 33) than without liver metastasis or recurrence in the liver (16% of 40 patients) (P0.001). Moreover, the risk of recurrence in the liver during long-term follow-up was significantly increased by VEGF-A production only in patients with Dukes C (N46) [odds ratio (OR)22.4; 95% confidence interval (CI): 4.6‐108], but not in Dukes B (N24). In multiple logistic regression analysis using variables of age, gender, expression of FGF2, CD34, p53, stage of lymph node metastasis, and lymph/vascular vessel invasion in pathological specimen, expression of VEGF-A was sole significant factor (OR43.5; 95%CI: 4.2‐448). In Kaplan-Meier survival curves, 5-year survival in VEGF-A positive and negative patients belong to Dukes C was 68% and 93% (log-rank test: P0.05), respectively. Hazard ratio of VEGF-A adjusted by age and gender was 4.3; 95%CI: 1.2‐15.5. Conclusions These results suggest that patients with Dukes C colorectal cancer and VEGF-A positive in tumor specimen may have a higher risk of recurrence in the liver during long term follow-up.