title: Development of novel tools for the diagnosis and prognosis of pheochromocytoma using peptide marker immunoassay and gene expression profiling approaches.
abstract: Pheochromocytomas (PHEOs) are rare catecholamine-producing neoplasias that arise from chromaffin cells of the adrenal medulla or from extra-adrenal locations. These neuroendocrine tumors are usually benign, but may also present as or develop into a malignancy. There are currently no means to predict or to cure malignant tumors which have a poor prognosis. We have recently validated several assays for the measurement of peptides derived from chromogranin A (CgA) and secretogranin II (SgII) in order to determine whether these secreted neuroendocrine products could provide useful, complementary markers for the diagnosis and prognosis of PHEOs. Both the CgA-derived peptide WE14 and the SgII-derived peptide EM66 proved to be sensitive circulating markers for the diagnosis of PHEO. In addition, much higher EM66 levels were measured in benign than in malignant tumoral tissues, suggesting that this peptide could represent a valuable tool for the prognosis of PHEO. We have also initiated a comparative microarray study of benign and malignant PHEOs, which allowed the identification of a set of about 100 genes that were differentially expressed and best discriminated the two types of tumors. A large majority of these genes were expressed at lower levels in the malignant disease and were associated with various characteristics of chromaffin cells, such as hormone secretion signaling and machinery, peptide maturation, and cellular morphology. Altogether, these studies provide novel tools for the management of PHEO, and new insights for the understanding of tumorigenesis in chromaffin cells, which may offer potential therapeutic strategies.
authors.affiliation: INSERM U413, Laboratory of Cellular and Molecular Neuroendocrinology, European Institute for Peptide Research (IFRMP23), University of Rouen, and Department of Genetics, Hôpital Européen Georges Pompidou, Paris, France. youssef.anouar@univ-rouen.fr
authors.forename: Youssef
authors.initials: Y
authors.lastname: Anouar
authors.forename: Laurent
authors.initials: L
authors.lastname: Yon
authors.forename: Johann
authors.initials: J
authors.lastname: Guillemot
authors.forename: Erwan
authors.initials: E
authors.lastname: Thouennon
authors.forename: Laure
authors.initials: L
authors.lastname: Barbier
authors.forename: Anne-Paule
authors.initials: AP
authors.lastname: Gimenez-Roqueplo
authors.forename: Jerome
authors.initials: J
authors.lastname: Bertherat
authors.forename: Herve
authors.initials: H
authors.lastname: Lefebvre
authors.forename: Marc
authors.initials: M
authors.lastname: Klein
authors.forename: Mihaela
authors.initials: M
authors.lastname: Muresan
authors.forename: Eric
authors.initials: E
authors.lastname: Grouzmann
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Plouin
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Elkahloun
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010673:Pheochromocytoma / Q000235:genetics*