{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:18:06Z","timestamp":1792167486344,"version":"4.4.0"},"reference-count":61,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,1,21]],"date-time":"2003-01-21T00:00:00Z","timestamp":1043107200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microscopy Res &amp;amp; Technique"],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Von Hippel\u2010Lindau (VHL) disease is an uncommon, autosomal dominant hereditary multitumor syndrome caused by germline alterations of the <jats:italic>VHL<\/jats:italic> gene, which has been cloned recently and identified as a tumor suppressor gene. The major lesions in VHL disease include hemangioblastomas in the central nervous system and retina, clear cell renal cell carcinomas, pheochromocytomas, pancreatic tumors, epididymal cystadenomas, endolymphatic sac tumors, carcinoid tumors, and multiple cysts of the kidney, pancreas, and epididymis. Compared with sporadic ones, the tumors in VHL disease develop at an earlier age and often multifocally. Histologic features of VHL tumors are characterized by their high degree of vascularization and the presence of a clear cell component. Hypervascularization is induced by overexpression of vascular endothelial growth factor (VEGF), and because the principal function of VHL protein is the negative regulation of hypoxia\u2010inducible mRNAs including VEGF mRNA, inactivation of <jats:italic>VHL<\/jats:italic> gene plays critical roles in angiogenesis of the VHL tumors. In addition, since VHL protein is also required for the down\u2010regulation of transcription activity of certain genes for the cell growth and cell cycle, inactivation of <jats:italic>VHL<\/jats:italic> gene may contribute to tumorigenesis of the VHL tumors. A significant difference in the frequency of types of <jats:italic>VHL<\/jats:italic> gene mutation has been noted among the affected families, known as the genotype\u2010phenotype correlations. Microsc. Res. Tech. 60:159\u2013164, 2003. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jemt.10253","type":"journal-article","created":{"date-parts":[[2003,1,22]],"date-time":"2003-01-22T17:15:54Z","timestamp":1043255754000},"page":"159-164","source":"Crossref","is-referenced-by-count":32,"title":["Von Hippel\u2010Lindau disease"],"prefix":"10.1002","volume":"60","author":[{"given":"Toshiaki","family":"Sano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidehisa","family":"Horiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,1,21]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"2210","article-title":"Transforming growth factor beta1 is a target for the von Hippel\u2010Lindau tumor suppressor and a critical growth factor for clear cell renal carcinoma","volume":"59","author":"Ananth S","year":"1999","journal-title":"Cancer Res"},{"key":"e_1_2_1_3_1","first-page":"271","article-title":"Histogenesis of stromal cells in cerebellar hemangioblastomas. 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