Expression of angiogenesis-related factors in glioblastoma and peritumor tissue

Glioblastoma (GBM) is characterized by extensive angiogenesis, mostly triggered by tumor hypoxia. We previously reported that in GBM and peritumor tissue microvessels show a similar morphology and endothelial cells express CD105, the best marker for newly-formed tumor vessels. In this study, to better understand the role played by angiogenesis in GBM progression, the expression of HIF-1α and -2α, VEGF and its receptors (VEGFR-1 and -2) in GBM and in peritumor tissue was investigated. Tissue samples were obtained from fifty patients. In paraffin-embedded specimens, derived from enhanced lesions (first area) of GBM and white matter at a distance ≤1 mm from the tumor edge (second area), the expression of HIF-1α and -2α, VEGF, VEGFR-1 and -2 was evaluated by immunohistochemistry. Immunoreactivity for all markers was detected not only in the tumor, but also in the peritumor tissue and it was present in neoplastic cells, in endothelium and in apparently normal glial cells. HIF-1α and -2α expression was mainly confined in the nuclei. VEGF, localized in the cytoplasm, showed diffused expression with intense staining in the first area. VEGFR-1 and -2 immunopositivity was dominantly observed at the membrane level. A significant difference in the expression of VEGF and VEGFR-2 between GBM and peritumor tissue was observed. The high heterogeneity in the expression of the other molecules might explain the absence of significant differences between the first and second area. No correlation was observed between the analyzed molecules and survival time. Our study demonstrates that HIF-1α, HIF-2α, VEGF and its receptors are present in peritumor areas, probably reflecting the reduced oxygen availability. Since the response to anti-VEGF therapy is transient and the majority of patients relapse, our findings may lead to consider the molecules expressed in the peritumor tissue as a target for new treatments counteracting angiogenesis. Supported by FIRB Accordi di Programma 2010