title: Coexpression of erythropoietin and its receptor in endolymphatic sac tumors.
abstract: OBJECTIVE
  Von Hippel-Lindau (VHL) disease is characterized by multiple tumors in specific organs. The cell of origin and the reason for the particular organ distribution of the tumors remains unknown. Endolymphatic sac tumor (ELST) is one of the lesions associated with VHL disease. Data from previous studies of VHL disease-associated hemangioblastomas (HBs) and renal cell carcinomas (RCCs) have indicated that VHL gene deficiency causes coexpression of erythropoietin (Epo) and its receptor (Epo-R), which facilitates tumor growth.
  
  
  METHODS
  The authors studied ELSTs from five patients with VHL germline mutations. Analysis of the five ELST samples revealed loss of the wild-type allele, consistent with Knudson's two-hit hypothesis for tumorigenesis. All five ELST specimens were characterized microscopically and by immunohistochemical analysis. Coexpression of Epo and Epo-R was found in all five tumors on immunohistochemical studies and confirmed through reverse transcription-polymerase chain reaction and Western blot analysis.
  
  
  CONCLUSIONS
  Expression of Epo appears to be a result of VHL gene deficiency, whereas the simultaneous coexpression of Epo-R may reflect a developmental mechanism of tumorigenesis. Coexpression of Epo and Epo-R in ELSTs together with the morphological and genetic similarities of these lesions with other VHL disease-associated tumors indicates that VHL disease-associated tumors in different organs share common pathogenetic pathways.
authors.affiliation: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Timothy W A
authors.initials: TW
authors.lastname: Vogel
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Vortmeyer
authors.forename: Irina A
authors.initials: IA
authors.lastname: Lubensky
authors.forename: Youn-Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Makoto
authors.initials: M
authors.lastname: Furuta
authors.forename: Barbara
authors.initials: B
authors.lastname: Ikejiri
authors.forename: H Jeffrey
authors.initials: HJ
authors.lastname: Kim
authors.forename: Russell R
authors.initials: RR
authors.lastname: Lonser
authors.forename: Edward H
authors.initials: EH
authors.lastname: Oldfield
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
mesh_terms: D000328:Adult; D004428:Ear Neoplasms / Q000235:genetics* / Q000473:pathology*; D004712:Endolymphatic Sac / Q000473:pathology*; D004921:Erythropoietin / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017467:Receptors, Erythropoietin / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006623:von Hippel-Lindau Disease
chemical_list: D017467:Receptors, Erythropoietin; D004921:Erythropoietin