Abstract
Background: Angiogenesis plays an important role in progression of colorectal carcinoma (CRC). Evidence from preclinical and clinical studies indicates that vascular endothelial growth factor (VEGF) is the predominant angiogenic factor in CRC. Indeed, VEGF is expressed in approximately 50% of CRCs, with minimal to no expression in normal colonic mucosa and adenomas. In this study, the expression of VEGF-1 was examined in stage I-IV CRCs to determine its clinicopathological correlates, and association with the response to treatment and disease outcome. Patients and Methods: The present series consisted of tissue samples obtained from 360 patients with stage I, II, III, or IV CRC who had undergone large bowel resection during 1981-1990 at Turku University Hospital. Archival paraffin-embedded CRC tissue samples were used to build up tissue microarray (TMA) blocks and VEGF-1 expression was assessed immunohistochemically using an automated staining system. Three different grading systems were applied to evaluate the expression of VEGF-1. Results: Seventy percent of patients with stage IV CRC had positive VEGF-1 expression, while 50% and 47%, respectively of patients with stage H and III CRC had positive VEGF-1 expression (p=0.005). VEGF-1 expression in the left colon and rectum was significantly higher than that in the right colon (61% vs. 45%, respectively) (p=0.006). Significant statistical correlation (p=0.04) was found between VEGF-1 and 10-year disease-specific survival: patients who died of the disease more frequently had a VEGF-1-expressing tumour than did those who survived for 10 years. Conclusion: Quantification of VEGF-I expression seems to provide valuable prognostic information in CRC, particularly in selecting those patients at high risk for disease progression who are likely to benefit from adjuvant therapy.