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.
See also Somatostatin in oncology, the overlooked evidences.
Supplementary Data