Microvessel Density, Cyclo-Oxygenase 2 Expression, K-Ras Mutation and P53 Overexpression in Colonic Cancer

Background: Tumour angiogenesis, cyclo-oxygenase (COX) 2 expression, K- ras mutation and p53 overexpression are commonly involved in colorectal tumorigenesis, but their interrelationship and clinicopathological effects remain inconclusive. Methods: Clinicopathological data from 114 consecutive patients with primary stage III colorectal cancer were evaluated prospectively. Microvessel density ( MVD) of the tumour was defined by counting the number of microvessels in hotspots, visualized by inummocytochemical staining of endothelial CD34. K-ras mutation was analysed by the restriction enzyme cleavage method. COX-2 expression and p 53 overexpression were determined by immunocytochemistry. Results: Increased MVD in hotspots was significantly associated with COX-2 expression (P < 0.001), K-ras mutation (P = 0.007) and p53 overexpression (P = 0.006 ). COX-2 expression was not associated with either K-ras mutation or p53 overexpression. Clinicopathologically, greater MVD and COX -2 expression were significantly associated with vascular invasion of cancer cells (MVD, P = 0.027 and COX-2 expression, P = 0.006), but p53 overexpression and K-ras mutation were not. Multivariate analysis indicated that greater MVD (P = 0.002) and p53 overexpression (P = 0.016) were significant independent predictors of tumour recurrence, whereas COX- 2 expression (P = 0.634) and K-ras mutation (P = 0.356) were not. Conclusion : Tumour angiogenesis may be associated with tumour metastasis and is significantly influenced by K-ras mutation , p53 overexpression and COX-2 expression in patients with colonic cancer