Correlation of bFGF, FGFR-1 and VEGF expression with vascularity and malignancy of human astrocytomas

OBJECTIVE: To investigate the correlation of angiogenic factor expression levels with the degrees of malignancy and vascularity and their clinicopathologic significance in astrocytomas. STUDY DESIGN: Factor VIII-related antigen (FVIII-RAg) was used as the marker of endothelia and basic fibroblast growth factor (bFGF); FGF receptor (FGFR)-1 and vascular endothelial growth factor (VEGF) were qualitatively and quantitatively detected with immunohistochemistry and image analysis in 61 brain astrocytomas. The correlation with tumor grades, angiogenesis and prognosis was studied. RESULTS: Measurement of FVIIIRAg expression could describe endothelial proliferation and vascularity, which were related to grade of tumor and prognosis. bFGF and VEGF expression levels in neoplastic astrocytes and endothelia were significantly different in various grades of astrocytoma. These angiogenic factors affected the positive reaction areas and integral optical densities of FVIII-RAg as well as survival time. In contrast, the expression of FGFR-1 was related to neither bFGF nor FVIIIRAg and had no significant effect on tumor malignancy. CONCLUSION: Positive regulation by bFGF and autocrine/paracrine VEGF contributes to the growth and angiogenesis of astrocytomas. Measurement of endothelial cell proliferation with FVIIIRAg in tumor stroma and quantitative detection of angiogenic factor levels in neoplastic cells had prognostic value in brain astrocytomas. The results also indicate that inhibiting bFGF and VEGF expression and/or blocking their effects could be a very useful therapeutic strategy for malignant gliomas.