High expression of dopamine receptor subtype 2 in a large series of neuroendocrine tumors

• Published in: Cancer biology & therapy Vol. 7; no. 12; pp. 1970 - 1978
• Main Authors: Grossrubatscher, Erika, Veronese, Silvio, Dalino Ciaramella, Paolo, Pugliese, Raffaele, Boniardi, Marco, De Carlis, Luciano, Torre, Massimo, Ravini, Mario, Gambacorta, Marcello, Loli, Paola
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01-12-2008
• Subjects: Adult; Aged; Binding; Biology; Bioscience; Calcium; Cancer; Carcinoma, Bronchogenic - genetics; Carcinoma, Bronchogenic - metabolism; Cell; Cell Division; Cycle; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Landes; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Neuroendocrine Tumors - genetics; Organogenesis; Pancreas - cytology; Pancreas - physiology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Pituitary Neoplasms - genetics; Pituitary Neoplasms - pathology; Proteins; Receptors, Dopamine D2 - genetics; Receptors, Dopamine D2 - metabolism
• ISSN: 1538-4047; 1555-8576
• DOI: 10.4161/cbt.7.12.6957

Background/Aims: Recent data in vitro and in vivo support that dopaminergic drugs might exert an inhibitory effect on hormone secretion and, possibly, on tumor growth in neuroendocrine tumors (NET)s. Their potential therapeutic role needs the demonstration of dopamine receptors (DR) in tumor cells. Little is known on the expression of DR in NETs. Aim: to evaluate by immumohistochemistry the presence of DR subtype 2 (D2R) in well differentiated NETs of different sites and in normal islet cells. Methods: 46 NET samples from 44 patients and normal endocrine pancreatic tissue were studied. D2R-staining was performed on NETs and compared with six non-secreting pituitary adenomas and related to clinical-pathological data. Results: 85% of samples (100% of bronchial carcinoids and 93% of islet cell tumors) showed positivity for D2R; intensity of immunoreaction in NETs was similar or higher than in pituitary (54% and respectively 31% of cases). D2R positivity in more than 70% of tumor cells was observed in 46% of samples. Same intensity of D2R-immunoreactivity was found in pituitary and normal islet cells. No differences in D2R expression were recorded on considering tumor grading, size, proliferative activity, presence of metastases, endocrine activity and gender. A significant difference (62,5% vs 96,4%, P=0,039) was observed in the prevalence of D2R expression between patients with more aggressive tumors and patients without recurrence/progression of disease during follow-up. Conclusion: The present data demonstrate a high expression of D2R in NETs; this finding is of clinical relevance in view of the potential role of dopaminergic drugs in inhibiting secretion and/or cell proliferation in NETs.