Clinicopathologic significance of p53, hypoxia-inducible factor 1 alfa, and vascular endothelial growth factor expression in colorectal cancer.

Abstract

3609 Background: Hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) are correlated with angiogenesis and involved in tumor growth and metastases. P53 gene mutation is well established pathways in carcinogenesis and related to angiogenesis. The aim of this study was to evaluate the prognostic significances of the expressions of p53, HIF- 1α, and VEGF in colorectal cancer. Methods: The tumor tissues of 311 patients with colorectal carcinoma that underwent potentially curative resection were investigated immunohistochemically using monoclonal antibodies against p53, HIF-1α, and VEGF. Clinical information and disease-free survival and overall survival were evaluated with respect to the expressions of p53, HIF-1α, and VEGF. Results: Median follow-up duration was 48 months, and median patient age was 60 ± 11 years (range 22-82). Positivity rates of p53, HIF-1α, and VEGF were 42.4%, 63.0%, and 56.6%, respectively. HIF-1α expression in tumor tissue was found to be significantly correlated with the expression of VEGF (p = 0.040), and depth of invasion (p = 0.019). Positive relationships were found between the expressions VEGF and vascular invasion (p = 0.037), and CEA (p = 0.005), p53 expression was related to vascular invasion (p = 0.011), and CEA (p = 0.026). Univariate analysis showed that stage (p < 0.001), vascular invasion (p < 0.001), CEA (p < 0.001), and HIF-1α expression (P = 0.033) were associated with disease free survival. Stage (p < 0.001), vascular invasion (p = 0.010), CEA (p < 0.001), histological grade (p = 0.038), and HIF-1α expression (p = 0.001) were significant variables affecting overall survival. Multivariate analysis showed that stage and CEA were independently associated with disease free survival (p = 0.006, p < 0.001, respectively), and overall survival (p = 0.001, p = 0.003, respectively). HIF- 1α was independently associated with a poor overall survival (p = 0.002), however, p53 and VEGF were not found to be related to prognosis. Conclusions: HIF-1α expression in tumor tissue is associated with angiogenesis and a poor overall survival in colorectal cancer patients. No significant financial relationships to disclose.