title: Expression of somatostatin receptors, dopamine D₂ receptors, noradrenaline transporters, and vesicular monoamine transporters in 52 pheochromocytomas and paragangliomas.
abstract: While somatostatin receptors (sst), through somatostatin-radiolabeled analogs, are used, mainly in second line, in the diagnosis and treatment of pheochromocytomas (PCC) and paragangliomas (PGL), the clinical significance of dopamine receptor subtype 2 (D₂) in PCC/PGL is unknown. Indeed, radiolabeled dopamine (DA) analogs such as fluorine 18 ((18)F)-DA, used for positron emission tomography in PCC localization, are mainly correlated to the presence of noradrenaline transporter (NAT) and vesicular monoamine transporters (VMAT) but not to D₂. The aim of this study was to quantitate D₂ and sst expression in 52 PCC/PGL and to compare it with that of 35 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Quantitative RT-PCR of sst(1-3) and sst₅, D₂, NAT, VMAT1/2 was performed in all tumors, while immunohistochemistry analysis of sst₂ and D₂ was performed in seven tumors. D₂ mRNA was expressed in all PCC/PGL. Mean expression was significantly higher in PCC/PGL than in GEP-NETs (4.8 vs 0.5 copy/copy β-glucuronidase (Gus)). sst₂ and sst(1) were expressed in most PCC/PGL, with sst(2)-dominant expression (mean mRNA: 1.6 vs 0.4 copy/copy β-Gus). sst₂ expression level was similar to that of GEP-NETs, whereas sst₅ expression level was significantly lower (0.12 vs 0.78 copy/copy β-Gus). Our study evidenced strong D₂ mRNA expression in PCC and for the first time in PGL. PCC/PGL express sst₂ mRNA at levels similar to those of GEP-NETs. New drugs can target ssts and D₂ more efficiently than current somatostatin analogs. Moreover, transporters like NAT and VMAT1/2, could be co-targeted with sst, as a basis of new radionuclide compounds in the imaging and treatment of these tumors.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Centre Hospitalo-Universitaire Conception, 147 Boulevard Baille, 13385 Marseille, France.
authors.forename: Alexandru
authors.initials: A
authors.lastname: Saveanu
authors.forename: Mihaela
authors.initials: M
authors.lastname: Muresan
authors.forename: Catherine
authors.initials: C
authors.lastname: De Micco
authors.forename: David
authors.initials: D
authors.lastname: Taieb
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Germanetti
authors.forename: Frederic
authors.initials: F
authors.lastname: Sebag
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Henry
authors.forename: Laurent
authors.initials: L
authors.lastname: Brunaud
authors.forename: Alain
authors.initials: A
authors.lastname: Enjalbert
authors.forename: Georges
authors.initials: G
authors.lastname: Weryha
authors.forename: Anne
authors.initials: A
authors.lastname: Barlier
mesh_terms: D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010235:Paraganglioma / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D017481:Receptors, Somatostatin; C493449:SLC18A1 protein, human; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins