Somatostatin and Dopamine Receptor Profile of Gastroenteropancreatic Neuroendocrine Tumors: An Immunohistochemical Study

Somatostatin and its synthetic analogs act through five specific somatostatin receptors (sstr1–5), found on the cell membrane of various tumors, including endocrine ones. Dopamine—a known neurotransmitter—acts through five membranous dopamine receptors (D1R–D5R) which have recently been found to be expressed in endocrine tumors. We evaluated the immunohistochemical expression of the sstrs and D2R in a large series of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A total of 22 (28.94%) well-differentiated NETs (WDNETs), 6 (7.89%) WDNETs of uncertain biology, 26 (34.21%) well-differentiated neuroendocrine carcinomas, and 22 (28.94%) poorly differentiated neuroendocrine carcinomas were studied. Overall, 76.31% of the tumors were positive for different types of sstrs with variable intensity of the membranous staining whereas 36.95% were positive for D2R alone. The sstr2A was the most frequently expressed, followed by sstr2B, sstr1, and sstr5. Co-expression of sstrs and D2R was seen in 88.23% of positive tumors. The high rates of sstr2A and sstr2B and in a lower extent of sstr5 expression are of great importance for more accurate imaging, staging and targeted therapy of the disease. The co-expression of sstrs and D2R in a significant number of the studied cases offers a potential therapeutic alternative for GEP-NETs.