Angiogenesis (the growth of new blood vessels) is important for tumour invasion and metastasis in order for a tumour to grow beyond a few millimetres in size. Vascular endothelial growth factor (VEGF) is thought to be the predominant angiogenic factor in colorectal and other cancers. As a result, numerous studies have looked at VEGF expression in colorectal cancer patients and several therapeutic agents have been trialled that target the VEGF pathway.
VEGF levels were determined in 100 paired tumour and normal colorectal tissue samples (1998-2001) and 75 pre-operative plasma samples (2000-2002) by ELISA. Tissue (pg/mg protein) and plasma VEGF levels (pg/ml) were correlated with the tumour pathology. Survival analysis was performed for disease-free and overall 15-year survival (Kaplan Meier, p < 0.05). The study had ethics approval.
VEGF levels were significantly up-regulated in colorectal tumour tissue compared to normal tissue. The median VEGF levels were 288 (range, 30-4,156) pg/mg protein for tumour, 38 (0-833) for normal colon and 90 (0-1,262) pg/ml for pre-operative plasma samples. Tumour levels of VEGF correlated with the tumour depth, differentiation and whether the tumour had undergone lymphatic invasion e.g. well differentiated, 230 (79-1,348), moderate 392 (30-4,156) and poorly differentiated 685 (88-2,612)pg/mg protein. Plasma VEGF levels significantly correlated with tumour differentiation and vascular invasion,e.g. 211 (14-889) vascular invasion and 80 (0-785)pg/ml, no vascular invasion. The 15-year survival status for patients with tissue samples was 30% were alive and well, 1% was alive with recurrence and 69% had died. For the 75 plasma patients; 27% patients were alive and well with the remaining 67% having died. VEGF levels in plasma but not tissue samples significantly correlated with both disease-free and overall 15-year survival, with patients with low plasma VEGF levels having a better survival outcome (p < 0.05, Kaplan Meier).
VEGF levels in both colorectal tumour tissue and pre-operative plasma samples correlated with the tumour pathology. However, only pre-operative plasma VEGF levels correlated with disease-free and overall 15-year survival.
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