Immunohistochemical detection of hypoxia-induced factor-alpha in endolymphatic sac tumors

Abstract Problem: Endolymphatic sac tumor (ELST) is a rare vascular neoplasm associated with von Hippel-Landau disease, an autosomal dominant multitumor syndrome characterized by highly vascular tumors. The von Hippel-Landau (VHL) gene is located on chromosome 3p25 and encodes the VHL tumor suppressor protein, which plays a critical role in the degradation of HIF-1a. HIF-1a regulates vascular endothelial growth factor (VEGF)-mediated angiogenesis. The lack of degradation of HIF-1a due to a nonfunctioning VHL protein is thought to play a role in the proliferation of tumors associated with VHL syndrome. The goals of this study are to present clinical and radiological presentations of 3 patients with ELSTs and report on the HIF-1a overexpression in ELST cells. Methods: Our study consisted of chart and radiological review and immunohistochemical analysis. Specimens from 3 patients with pathologically confirmed ELST were analyzed for the presence of the HIF-1a protein using imunohistochemistry with a specific monoclonal antibody as previously described (Zagzag et al, Cancer 2000). Results: All patients presented with nonspecific findings seen with other temporal bone-related lesions of ipsilateral tinnitus and hearing loss. One patient was evaluated at a late stage who also presented with facial nerve weakness. Immunohistochemical analysis in all specimens confirmed overexpression of the HIF-1a protein in tumor cells. Conclusion: ELSTs are likely to be associated with HIF-1a mediated angiogenesis. These lesions are possibly associated with loss of VHL protein due to mutation of the VHL gene. Significance: Elucidation of the pathophysiology of endolymphatic sac tumors may lead to future novel approaches in the management of this unusual tumor associated with von Hippel-Lindau disease. Support: None reported.