Expression of vascular endothelial growth factor (VEGF) and its two receptors in diffusely infiltrating astrocytomas and relationship to proliferative activity of tumor cells.

We studied the relationships among vascular endothelial growth factor (VEGF), its receptors (Flt1 and Flk1), and MIB-1. Their expression in 47 diffusely infiltrating astrocytomas obtained at surgery or autopsy was investigated by the ABC method and analyzed quantitatively. The positive rate of VEGF in tumor cells was higher than that in endothelial cells, and Flk1 was lower in tumor cells (P < 0.01, 0.01), whereas Flt1 in both tumor cells and endothelial cells was found at similar levels (P > 0.05). In tumor cells, VEGF became high with increased histological grades (P < 0.01). whereas both Flt1 and Flk1 were higher in grade 4 than in grades 2 and 3 (P < 0.01, 0.05). VEGF, Flt1, and Flk1 in endothelial cells were also highly expressed in grade 4 (P < 0.01). The distribution of MIB-1-positive nuclei in grade 4 was similar to VEGF, and the percent of positivity from grade 2 to grade 4 also increased (P < 0.01). There was a linear positive correlation between VEGF and both Flt1 and Flk1 in both tumor cells and endothelial cells (P < 0.01). So was the percent of positivity with VEGF, Flt1, and Flk1 in tumor cells and endothelial cells (P < 0.01). The experiment suggests that VEGF may act as a growth factor for both endothelial cells and tumor cells. VEGF, Flt1, and Flk1 can be considered as indicators of the malignancy potential of diffusely infiltrating astrocytomas. The expression of VEGF and the two receptors may be affected by the proliferative activity of tumor cells.