Abstract
Neuroblastoma (NB) is an extra-cranial solid neoplasm in childhood. Genetic markers as MYCN amplification (MNA) and deletion of 11q (11q ) are considered factors with an adverse prognosis. Usually, an inverse relationship between MNA and 11q is found. Approximately 13% of the MNA cases present with 11q . These cases show a dramatic decline in survival rates. Hypoxia-inducible factor-2a (HIF-2a) protein expression has been described as an indicator of poor outcome, has been correlated with an aggressive phenotype in NB, and serves as a marker for stem cell-like phenotypes. Additionally, HIF-2a positive cells strongly express vascular endothelial growth factor (VEGF) and, as such, could be involved in tumor angiogenesis. Our objective was to study the prognostic impact of HIF-2a and VEGF in the group of NB with MNA and 11q . In total, 31 cases of NB with MNA (8 cases with 11q and 23 without 11q ) were analyzed by HIF-2a and VEGF immunohistochemistry. The status of the corresponding genetic markers was analyzed by Fluorescence In Situ Hybridization (FISH) and/or Multiple Ligation Probe Amplification (MLPA). Calculations were performed using SPSS Statistics 17.0. In a total of 54 NMA cases with a known 11q status, 14 presented 11q . Tumor sections from 31 of these cases were further investigated by HIF-2a and VEGF immunohistochemistry. A low number (4/23; 17.4%) of MNA cases without 11q showed medium/high HIF-2a immunoreactivity, as opposed to a high number (5/8; 62.5%) of cases present in the MNA group with 11q . A high percentage (87.5%) of MNA cases with 11q presented with a high expression of VEGF. In conclusion, HIF-2a and VEGF protein expression is observed frequently in NB cases with MNA and 11q , further implicating HIF-2a in NB progression and aggressive disease. Supported by: FIS PI06/1576, RD06/ 0020/0102 (Instituto de Salud Carlos III) and Asociacion Espanola Contra el Cancer. GENE AMPLIFICATION AS DOUBLE MINUTES OR HSR IN SOLID TUMORS: ORIGIN AND STRUCTURE
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