Expression of VEGF and bcl-2 in Olfactory Neuroblastoma: Association with Microvessel Density

• Main Authors: Diensthuber, Marc, Potinius, Marc, Stan, Alexandru-C., Samii, Madjid, Lenarz, Thomas, Stöver, Timo
• Format: Conference Proceeding
• Language: English
• ISSN: 1531-5010; 1532-0065
• DOI: 10.1055/s-2009-1222413

Introduction: Olfactory neuroblastoma (ONB) is a rare malignant tumor that is believed to arise from the olfactory epithelium in the vault of the nasal cavity. Neoangiogenesis plays a fundamental role in the pathogenesis and progression of malignant solid tumors and this process is controlled by angiogenic growth factors. A number of angiogenic factors, including vascular endothelial growth factor (VEGF), have been shown to be expressed in neuroblastic tumors. In hypoxic conditions, VEGF expression is regulated via hypoxia-inducible factor (HIF)-1a and bcl-2. Activation of the VEGF receptors (VEGF-R1/R2) by VEGF promotes neoangiogenesis in various malignant tumors. Methods: Expression of HIF-1a, VEGF, VEGF-R1, VEGF-R2, and bcl-2 was studied by immunohistochemistry in a series of 19 olfactory neuroblastoma samples. Data were correlated with microvessel density, proliferative activity, and apoptosis in the specimens, and survival analysis was performed to investigate the prognostic value of the examined factors. Results: Immunohistochemical analysis revealed robust expression of HIF-1a, VEGF, VEGF-R1/-R2, and bcl-2 in ONB. A significant positive correlation between the expression levels of VEGF and bcl-2 was found. Expression of both factors was associated with microvessel density of the tumors. Survival analysis did not reveal any prognostic significance for the tested factors. Conclusion: Expression of HIF-1a, VEGF, VEGF-R1/-R2, and bcl-2 may play a functional role in ONB pathogenesis. Our data suggest that bcl-2 regulates VEGF expression, and both factors may promote angiogenesis in ONB. Thus, these factors represent potential targets for antiangiogenic treatment strategies in the therapy of ONB.