Department of Pathology and Department of Surgery^*, The University of Hong Kong, Queen Mary Hospital, Hong Kong

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic factor, which is up-regulated in most glioblastoma multiforme (GBM). Less attention has been given to VEGF and its receptors expression in ependymomas (Epen) and oligodendrogliomas (Oligo), particularly during their anaplastic progression. Fifty-six gliomas, consisting of 10 Epen, 12 Oligo, 3 anaplastic Oligo, 6 grade II astrocytoma (Astro II), 5 anaplastic (grade III) Astro (Astro III) and 20 GBM, were investigated for the expression of VEGF and its receptors using in-situ hybridization and RT-PCR. VEGF was moderately to strongly upregulated in 8 of 10 Epen and in all anaplastic Oligo and GBM cases. All the tumours exhibited similar degrees of extensive necrosis and vascular proliferation with VEGF expression consistently seen in tumour cells around necrotic areas. In low grade lesions, VEGF was also expressed in 4 of 12 Oligo, 3 of 6 Astro II and 2 of 5 Astro III in a lower level, mostly with a focal distribution. VEGF receptors, Flt-1 and KDR, were also up-regulated in the tumour vasculature of anaplastic Oligo, Epen with necrosis, and in GBM. In summary, anaplastic progression in all three types of gliomas is heralded by the occurrence of small zones of VEGF-expressing cells and early vascular proliferation, followed by an accelerated phase of angiogenesis closely related to VEGF induction around areas of necrosis and the expression of VEGF receptors in the tumour vasculature.