EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AND ITS RECEPTOR, KDR, CORRELATES WITH VASCULARITY, METASTASIS, AND PROLIFERATION OF HUMANCOLON-CANCER

We studied the correlation between expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bPGF), and their receptors with vascularity, metastasis, and proliferative index of hu man colon cancers. Immunohistochemical analyses using antibodies again st VEGF, bFGF, their receptors (KDR, flt-1, bek, and flg), factor VIII , and proliferating cell nuclear antigen were carried out on archival specimens of 52 human colon carcinomas and 10 adenomas. Vessels were q uantitated by light microscopy (x200), and the intensity of staining f or VEGF and bFGF was assessed on a scale of 0-3+. The presence or abse nce of immunostaining for KDR, flt-1, bek and flg was evaluated in end othelial cells, and proliferation was determined by counting the numbe r of proliferating cell nuclear antigen-positive cells per 500 tumor c ells. Expression of VEGF and KDR was higher in metastatic than in nonm etastatic neoplasms and directly correlated with the extent of neovasc ularization and the degree of proliferation, whereas expression of bFG F, flt-1, bek, and flg did not differ among tumor types. Vessel counts mere greater in metastatic tumors than in nonmetastatic tumors. These findings support the hypothesis that VEGF is an important angiogenic factor in primary and metastatic human colon cancer. VEGF expression a nd vessel counts may aid in predicting patients at risk for metastasis from colon cancer.