Resumen de Immunoexpression patterns for Hypoxia-inducible Factor-1a and von Hippel-Lindau protein, in relation to Hsp90, of human brain tumors

Martha Assimakopoulou, Christina Androutsopoulou, Vassiliki Zolota, John Matsoukas

• The pathogenesis of many tumors, including brain tumors, has been associated with hypoxia, which induces the transcriptional activity of Hypoxia-inducible Factor-1a (HIF-1a). HIF-1a is normally degradated by the von Hippel-Lindau protein (pVHL) but, in hypoxia, pVHL/HIF-1a interaction is inhibited resulting in the nuclear accumulation of HIF-1a. Hsp90 (Heat shock protein 90), as a chaperone protein, plays a critical role for both stabilization of HIF-1a and degradation of pVHL. The aim of this study was to estimate immunohistochemically the expression levels of HIF-1a and pVHL, in relation to Hsp90, in different types of human brain tumors (42 gliomas, 9 medulloblastomas, and 38 meningiomas) using specific antibodies. The tumors were further divided into two groups according to the age of patients (>=19 years old or <19 years old). Nuclear, for HIF-1a, and cytoplasmic, for pVHL and Hsp90, localization was detected in a high percentage of tumor cells in the majority of tumors. In astrocytomas, a significant, grade-dependent relationship for HIF-1a immunoexpression was observed (p<0.05). Furthermore, there was a significant correlation between pVHL and Hsp90 immunoexpression (p<0.01). The group of >=19 years old patients with glioblastomas (WHO grade IV) demonstrated significantly increased immunoexpression for HIF-1a compared to pVHL (p<0.0001) and Hsp90 expression (p<0.01). In medulloblastomas, a significant correlation of HIF-1a with Hsp90 immunoexpression (p<0.05) was found. In meningiomas, no significant correlation for the expression of the three proteins was detected (p>=0.05). These results indicate that HIF-1a/pVHL/Hsp90 interactions may be implicated in biology of different types of brain tumors through different signaling mechanisms