Dopamine receptor expression and function in corticotroph ectopic tumors

Background: Dopamine receptor (DR) expression and dopamine agonist (DA) effectiveness have never been demonstrated in neuroendocrine tumors associated with ectopic ACTH syndrome (EAS). Aim: The aim of the current study was to evaluate DR and particularly D-2 subtype expression in neuroendocrine tumors associated with EAS and to evaluate the in vivo effectiveness of the DA cabergoline in the treatment of EAS. Patients and Methods: Six ACTH-secreting neuroendocrine tumors, including four lung, one pancreatic, and one thymic carcinoid, were used for the evaluation of D-2 expression by immunohistochemistry. DR subtypes and D-2 isoforms and number were evaluated by RT-PCR in three cases of persistent EAS after surgery. These patients were treated with cabergoline at the dose of 3.5 mg/wk for 6 months. Clinical parameters, hormonal levels, and tumor size were monitored during the treatment period. Results: At immunohistochemistry, D-2 was expressed in five (83.3%) tumors. At RT-PCR, D-2 was confirmed in all three cases but at variable numbers, whereas D-4 was expressed in two cases. D-2long was expressed in all three cases, together with D-2short in one case. A normalization of urinary cortisol levels was found in two patients (66.7%) after 3 months of treatment. However, treatment escape was demonstrated in one of these patients afterward. Conclusion: The results of this study demonstrated that DR are expressed in neuroendocrine tumors associated with EAS and that cabergoline treatment could be effective in controlling cortisol excess in a subgroup of patients with EAS. Further studies on a larger number of patients are mandatory to confirm the usefulness of DA in EAS.