Correlation between tumor vascularity, vascular endothelial growth factor production by tumor cells, serum vascular endothelial growth factor levels,and serum angiogenic activity in patients with breast carcinoma

Angiogenesis is an important prognostic factor in invasive breast carcinoma . We analyzed sera and tumor samples from 36 patients with primary breast c arcinomas to determine the relationship between tumor vascularity, Vascular endothelial growth factor (VEGF) production by tumor cells, levels of circ ulating VEGF (measured by ELISA assay), and levels of endothelial growth fa ctors analyzed by a functional test of human umbilical vein endothelial cel ls (HUVEC) proliferation. Tumor vascularity was correlated directly with VE GF production by the tumor, indicating that VEGF production is a relevant f actor in determining angiogenesis in primary tumor. No correlation was foun d either between the number of vessels in the tumor or the production of VE GF by tumor cells and the levels of serum angiogenic factors including VEGF . On the contrary, the two serum tests correlated together because a high s erum level of VEGF is more frequent in cases with the presence of HUVEC-sti mulating growth factors. These data indicate that the principal source of f actors stimulating angiogenesis in the primary tumor is the tumor itself. T his is an important issue in the context of anti-angiogenic therapeutic app roaches, which should be planned to interfere with tumor production of angi ogenic factors rather than with circulating angiogenic factors. In conclusi on. whereas the vessel count and VEGF production by tumor cells are paramet ers that give direct information on tumor angiogenesis, long-term follow-up is necessary to determine the clinical significance of the determination o f serum HUVEC-stimulating factors in the progression of breast carcinoma.