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Differential Assessment of Vascular Survival Ability and Tumor Angiogenic Activity in Colorectal Cancer

Departments of Pathology [A. G., E. S.], Surgery [G. M., A. P., C. M., C. S.], and Radiotherapy/Oncology [M. I. K.], Democritus University of Thrace, Alexandroupolis 68100, Greece

Background: The process of new vessel formation during neoplastic transformation and growth (neoangiogenesis) comprises proliferation, sprouting, and migration of endothelial cells within normal tissues adjacent to the tumor. These new vessels are directed toward the tumor invading edge and provide the bed for the subsequent growth of new tumor layers. We previously showed various degrees of decreasing vascular density in tumor layers once these lose contact with the normal tissue. This suggests that, apart from angiogenic factors, vascular survival factors contribute equally to the structure of the tumoral vasculature. This "vascular survival" potential can be assessed by comparatively examining the vascular density in peripheral and inner tumor areas.

Experimental Design: Using immunohistochemistry with the anti-CD31 monoclonal antibody, we assessed the tumor angiogenic activity (TAA) and vascular survival ability (VSA) in a sample of 242 patients with Dukes’ stage A (90 patients), B (73 patients), and C (79 patients) colorectal cancer treated with surgery alone.

Results: Overall, High TAA and VSA were significantly related with poor prognosis (P = 0.03; hazard ratio, 1.9 and P = 0.001; hazard ratio, 2.7, respectively). In multivariate analysis, VSA was revealed as the most potent and independent prognostic factor (P = 0.0001; t ratio, 4.5), followed by vascular invasion (P = 0.0001; t ratio, 4.4) and stage (P = 0.01; t ratio, 2.5). Tumors with high TAA and high VSA had a significantly higher risk to develop liver metastasis (P = 0.0003).

Conclusions: Assessment of VSA in addition to TAA provides additional important prognostic information in patients with colorectal cancer and can be a useful tool in the recruitment of patients who would benefit from angiostatic versus angiotoxic therapies.

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