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.