Dopamine receptor expression and function in corticotroph ectopic tumors.
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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 D2 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 D2 expression by immunohistochemistry. DR subtypes and D2 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, D2 was expressed in five (83.3%) tumors. At RT-PCR, D2 was confirmed in all three cases but at variable numbers, whereas D4 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.
- Middle Aged
- Reverse Transcriptase Polymerase Chain Reaction
- ACTH Syndrome, Ectopic/drug therapy/*metabolism
- Adrenocorticotropic Hormone/blood/secretion
- Ergolines/therapeutic use
- Lung Neoplasms/*secretion
- Neuroendocrine Tumors/*secretion
- Pancreatic Neoplasms/*secretion
- Receptors, Dopamine/*analysis/physiology
- Thymus Neoplasms/*secretion