Differential expression of erythropoietin and its receptor in von Hippel-Lindau-associated and multiple endocrine neoplasia type 2-associated pheochromocytomas

Timothy W.A. Vogel, Frederieke M. Brouwers, Irina A. Lubensky, Alexander Vortmeyer, Robert J. Weil, McClellan M. Walther, Edward H. Oldfield, W. Marston Linehan, Karel Pacak, Zhengping Zhuang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Pheochromocytoma is a neuroendocrine tumor associated with a variety of genetic disorders, which include von Hippel-Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis type 1, hereditary paraganglioma, and succinate dehydrogenase gene-related tumors. Previous studies of VHL-associated and MEN 2-associated pheochromocytomas suggest morphological, biochemical, and clinical differences exist among the tumors, but the process by which they develop remains unclear. Studies in other VHL-associated tumors suggest that VHL gene deficiency causes coexpression of erythropoietin (Epo) and its receptor (Epo-R), which facilitates tumor growth. The objective of this study was to understand the different process of tumorigenesis for VHL and MEN 2-associated pheochromocytomas. Ten pheochromocytomas (VHL patients n = 5, MEN 2 patients n = 5) were examined for the presence or absence of Epo and Epo-R using Western blot, immunohistochemistry, and RT-PCR analyses. Coexpression of Epo and Epo-R was found in all five VHL-associated pheochromocytomas; in contrast, expression of Epo-R, but not Epo, was documented in all five MEN 2-associated pheochromocytomas. Expression of Epo appears to be a result of VHL gene deficiency, possibly through activation of the hypoxia inducible factor-1 pathway, whereas Epo-R is an embryonal marker whose sustained expression in both VHL- and MEN 2-associated pheochromocytomas reflects an arrest or defect in development. These findings suggest an alternative process of tumorigenesis in VHL- and MEN 2-associated pheochromocytomas and implicate Epo as a clinical biomarker to differentiate these tumors.

Original languageEnglish (US)
Pages (from-to)3747-3751
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number6
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

Fingerprint

Multiple Endocrine Neoplasia Type 2a
Erythropoietin Receptors
von Hippel-Lindau Disease
Pheochromocytoma
Erythropoietin
Tumors
Genes
Neoplasms
Carcinogenesis
Neurofibromatosis 2
Hypoxia-Inducible Factor 1
Paraganglioma
Inborn Genetic Diseases
Neurofibromatosis 1
Succinate Dehydrogenase
Neuroendocrine Tumors
Biomarkers
Western Blotting
Chemical activation
Immunohistochemistry

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Differential expression of erythropoietin and its receptor in von Hippel-Lindau-associated and multiple endocrine neoplasia type 2-associated pheochromocytomas. / Vogel, Timothy W.A.; Brouwers, Frederieke M.; Lubensky, Irina A.; Vortmeyer, Alexander; Weil, Robert J.; Walther, McClellan M.; Oldfield, Edward H.; Linehan, W. Marston; Pacak, Karel; Zhuang, Zhengping.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 6, 01.06.2005, p. 3747-3751.

Research output: Contribution to journalArticle

Vogel, Timothy W.A. ; Brouwers, Frederieke M. ; Lubensky, Irina A. ; Vortmeyer, Alexander ; Weil, Robert J. ; Walther, McClellan M. ; Oldfield, Edward H. ; Linehan, W. Marston ; Pacak, Karel ; Zhuang, Zhengping. / Differential expression of erythropoietin and its receptor in von Hippel-Lindau-associated and multiple endocrine neoplasia type 2-associated pheochromocytomas. In: Journal of Clinical Endocrinology and Metabolism. 2005 ; Vol. 90, No. 6. pp. 3747-3751.
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AU - Weil, Robert J.

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