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To evaluate theprognostic significances of p53, hypoxia-inducible factor 1a (HIF-1a), and vascular endothelial growth factor (VEGF) expression in colorectal cancer.Tumour tissues of 311 colorectal carcinomas where a potentially curative resection was performed were assessed immunohistochemically using monoclonal antibodies against p53, HIF-1a, and VEGF. Clinicopathological relationships, disease-free and overall survival rates were evaluated with regard to p53, HIF-1a, and VEGF expression. The median follow-up was 48 months, and the median age was 60 (range 22-82) years.The rates found of p53, HIF-1a, and VEGF were 42.4%, 63.0%, and 56.6%, respectively. HIF-1a expression was correlated significantly with the expression of VEGF (P = 0.040) and depth of invasion (P = 0.019). Positive relationships were detected between the expressions of VEGF and vascular invasion (P = 0.037) and CEA (P = 0.005). p53 expression was associated with vascular invasion (P = 0.011) and CEA (P = 0.026). Multivariate analysis demonstrated that stage and CEA were associated independently with disease-free survival (P = 0.006, P < 0.001, respectively) and overall survival (P = 0.001, P = 0.003, respectively). HIF-1a was independently associated with unfavourable overall survival (P = 0.002), but p53 and VEGF were not related toprognosis.HIF-1a expression in tumour tissue is associated with angiogenesis and poor overall survival in colorectal cancer patients.