{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:07:01Z","timestamp":1770822421417,"version":"3.50.1"},"reference-count":88,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:p content-type=\"fine-print\"><jats:italic>Object.<\/jats:italic> Endolymphatic sac (ELS) tumors are low-grade malignancies of the temporal bone that are associated with von Hippel\u2014Lindau (VHL) disease but can also occur sporadically. The <jats:italic>VHL<\/jats:italic> gene product VHL protein is important in the regulation of hypoxia inducible factor (HIF)-1\u03b1, which controls expression of molecules that are important in angiogenesis and cell metabolism. In this study the authors examine the role of VHL and HIF-1 in ELS tumors.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Methods.<\/jats:italic> The ELS tumors from three patients were examined using the following method: DNA from tumor tissue was isolated, amplified by polymerase chain reaction and the <jats:italic>VHL<\/jats:italic> gene sequence was compared with the known wild-type sequence. Loss of heterozygosity (LOH) studies were performed to confirm the sequencing data. Immunohistochemical evaluation for VHL, HIF-1\u03b1, vascular endothelial growth factor (VEGF), and carbonic anhydrase IX (CA IX) was performed. Snap-frozen tumor tissue was examined using Western blot and HIF-1 immunoassays for HIF-1\u03b1 and VHL expression.<\/jats:p>\n<jats:p content-type=\"fine-print\">Two patients had sporadic ELS tumors and the other one suffered from VHL disease. Results of <jats:italic>VHL<\/jats:italic> gene sequencing were normal in the tissue derived from the sporadic ELS tumors. The ELS tumor, pheochromocytoma, and spinal hemangioblastoma were heterozygous for the same C-to-A transversion found in the germline carried by the patient with VHL disease. No LOH was detected in the tumor tissue obtained in the patient with VHL disease. Expression of HIF-1\u03b1, VEGF, and CA IX evaluated using immunohistochemical studies was elevated in the VHL-associated tumors. Nevertheless, Western blots and immunoassays for HIF-1\u03b1 did not show elevated expression in these tumors.<\/jats:p>\n<jats:p content-type=\"fine-print\"><jats:italic>Conclusions.<\/jats:italic> The sporadic and VHL disease\u2014associated ELS tumors in this study had normal VHL-mediated HIF-1 regulation. This is a result of normal <jats:italic>VHL<\/jats:italic> gene expression in the case of the sporadic ELS tumor. In the VHL-associated ELS tumor, this is due to one normal copy of the <jats:italic>VHL<\/jats:italic> gene and adequate <jats:italic>VHL<\/jats:italic> gene expression.<\/jats:p>","DOI":"10.3171\/jns.2004.100.3.0488","type":"journal-article","created":{"date-parts":[[2009,5,13]],"date-time":"2009-05-13T18:00:07Z","timestamp":1242237607000},"page":"488-497","source":"Crossref","is-referenced-by-count":27,"title":["Endolymphatic sac tumors in patients with and without von Hippel\u2014Lindau disease: the role of genetic mutation, von Hippel\u2014Lindau protein, and hypoxia inducible factor-1\u03b1 expression"],"prefix":"10.3171","volume":"100","author":[{"given":"Randy 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