Prognostic Significance of VEGF Expression Evaluated by Quantitative Immunohistochemical Analysis in Colorectal Cancer

Background: The prognostic value of vascular endothelial growth factor (VEGF) expression in colorectal cancer is still unclear, as shown by the discordant results still reported in the literature. The aim of the study was to examine the expression of VEGF in colorectal adenocarcinomas and investigate its prognostic relevance.

Materials And Methods: VEGF expression was investigated by immunohistochemistry performed on tissue microarrays, in a series of 117 colorectal cancer specimens. The VEGF staining intensity in the cytoplasm of tumor cells was quantified using a semi-automated computerized image analysis and correlated with various clinicopathological characteristics and survival.

Results: All tumors evaluated showed expression of VEGF, which were further divided into 49 high expression and 68 low expression tumors by their staining intensity. In tumors with lymph node metastasis, the intensity of staining of VEGF was more intense than in those without (P < 0.0001). Furthermore, the intensity of VEGF staining was more intense in Stage III tumors than those in Stage I/II (P < 0.0001). The mean number of involved lymph nodes in tumors with high VEGF staining intensity was significantly greater than in those with low staining intensity (P = 0.031). Survival analysis showed a significant correlation between high levels of VEGF staining intensity and poor disease-specific survival (P < 0.0001), with independent prognostic significance in multivariate analysis (RR = 3.5, P < 0.0001). In addition, patients with Stage II disease and high staining intensity of VEGF had a significantly worse disease-specific survival than those with low staining intensity (P = 0.001).

Conclusions: VEGF expression in colorectal cancer seems to be an independent prognostic marker of tumor behavior and may be useful to identify patients with unfavorable clinical outcome.