Coexpression of erythropoietin and its receptor in endolymphatic sac tumors

Timothy W.A. Vogel, Alexander Vortmeyer, Irina A. Lubensky, Youn Soo Lee, Makoto Furuta, Barbara Ikejiri, H. Jeffrey Kim, Russell R. Lonser, Edward H. Oldfield, Zhengping Zhuang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Object. 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.

Original languageEnglish (US)
Pages (from-to)284-288
Number of pages5
JournalJournal of neurosurgery
Volume103
Issue number2
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

Fingerprint

Endolymphatic Sac
Erythropoietin Receptors
von Hippel-Lindau Disease
Erythropoietin
Neoplasms
Carcinogenesis
Hemangioblastoma
Germ-Line Mutation
Renal Cell Carcinoma
Genes
Reverse Transcription
Western Blotting
Alleles

Keywords

  • Endolymphatic sac tumor
  • Erythropoietin
  • Erythropoietin receptor
  • Hemangioblastoma
  • Renal cell carcinoma
  • Tumorigenesis
  • Von Hippel-Lindau disease

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

Vogel, T. W. A., Vortmeyer, A., Lubensky, I. A., Lee, Y. S., Furuta, M., Ikejiri, B., ... Zhuang, Z. (2005). Coexpression of erythropoietin and its receptor in endolymphatic sac tumors. Journal of neurosurgery, 103(2), 284-288. https://doi.org/10.3171/jns.2005.103.2.0284

Coexpression of erythropoietin and its receptor in endolymphatic sac tumors. / Vogel, Timothy W.A.; Vortmeyer, Alexander; Lubensky, Irina A.; Lee, Youn Soo; Furuta, Makoto; Ikejiri, Barbara; Kim, H. Jeffrey; Lonser, Russell R.; Oldfield, Edward H.; Zhuang, Zhengping.

In: Journal of neurosurgery, Vol. 103, No. 2, 01.08.2005, p. 284-288.

Research output: Contribution to journalArticle

Vogel, TWA, Vortmeyer, A, Lubensky, IA, Lee, YS, Furuta, M, Ikejiri, B, Kim, HJ, Lonser, RR, Oldfield, EH & Zhuang, Z 2005, 'Coexpression of erythropoietin and its receptor in endolymphatic sac tumors', Journal of neurosurgery, vol. 103, no. 2, pp. 284-288. https://doi.org/10.3171/jns.2005.103.2.0284
Vogel, Timothy W.A. ; Vortmeyer, Alexander ; Lubensky, Irina A. ; Lee, Youn Soo ; Furuta, Makoto ; Ikejiri, Barbara ; Kim, H. Jeffrey ; Lonser, Russell R. ; Oldfield, Edward H. ; Zhuang, Zhengping. / Coexpression of erythropoietin and its receptor in endolymphatic sac tumors. In: Journal of neurosurgery. 2005 ; Vol. 103, No. 2. pp. 284-288.
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abstract = "Object. 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.",
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AU - Vogel, Timothy W.A.

AU - Vortmeyer, Alexander

AU - Lubensky, Irina A.

AU - Lee, Youn Soo

AU - Furuta, Makoto

AU - Ikejiri, Barbara

AU - Kim, H. Jeffrey

AU - Lonser, Russell R.

AU - Oldfield, Edward H.

AU - Zhuang, Zhengping

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N2 - Object. 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.

AB - Object. 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.

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