BACKGROUND/AIMS: Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic regulatory peptide highly expressed in the brain's appetite control centers, but also in peripheral neurons and in endocrine cells in the adrenal medulla, thyroid, pancreatic islets, and in the gastrointestinal tract. Plasma levels of CART were recently shown to be elevated in patients with neuroendocrine tumors (NETs), but the cellular sources of CART in NETs have remained unknown. The aim of the study was to establish whether CART is expressed in various types of NETs and, if so, to examine the frequency, distribution and phenotype of CART-expressing cells. METHODS: Tumor specimens from 133 NETs originating in the stomach, ileum, rectum, pancreas and thyroid were examined with immunohistochemistry and in situ hybridization. The expression of CART was quantified and the CART-expressing cells were phenotyped by double staining for established markers and hormones. RESULTS: CART-expressing tumor cells were found in the majority of the examined NETs. The expression pattern of CART was highly heterogeneous not only between tumors, but also within individual tumors. In 14% of the NETs, CART was found in a major population of the tumor cells. CONCLUSION: CART is produced in the majority of NETs, regardless of tumor origin. This likely explains the elevated levels of circulating CART in certain NETs patients, as recently described. CART could therefore prove to be a useful tool in the diagnostics of NETs not only in blood samples, but also in histopathological specimens.
BACKGROUND/AIMS: Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic regulatory peptide highly expressed in the brain's appetite control centers, but also in peripheral neurons and in endocrine cells in the adrenal medulla, thyroid, pancreatic islets, and in the gastrointestinal tract. Plasma levels of CART were recently shown to be elevated in patients with neuroendocrine tumors (NETs), but the cellular sources of CART in NETs have remained unknown. The aim of the study was to establish whether CART is expressed in various types of NETs and, if so, to examine the frequency, distribution and phenotype of CART-expressing cells. METHODS:Tumor specimens from 133 NETs originating in the stomach, ileum, rectum, pancreas and thyroid were examined with immunohistochemistry and in situ hybridization. The expression of CART was quantified and the CART-expressing cells were phenotyped by double staining for established markers and hormones. RESULTS:CART-expressing tumor cells were found in the majority of the examined NETs. The expression pattern of CART was highly heterogeneous not only between tumors, but also within individual tumors. In 14% of the NETs, CART was found in a major population of the tumor cells. CONCLUSION:CART is produced in the majority of NETs, regardless of tumor origin. This likely explains the elevated levels of circulating CART in certain NETs patients, as recently described. CART could therefore prove to be a useful tool in the diagnostics of NETs not only in blood samples, but also in histopathological specimens.
Authors: Mia Abels; Matteo Riva; Hedvig Bennet; Emma Ahlqvist; Oleg Dyachok; Vini Nagaraj; Liliya Shcherbina; Rikard G Fred; Wenny Poon; Maria Sörhede-Winzell; Joao Fadista; Andreas Lindqvist; Lena Kask; Ramasri Sathanoori; Marloes Dekker-Nitert; Michael J Kuhar; Bo Ahrén; Claes B Wollheim; Ola Hansson; Anders Tengholm; Malin Fex; Erik Renström; Leif Groop; Valeriya Lyssenko; Nils Wierup Journal: Diabetologia Date: 2016-06-23 Impact factor: 10.122
Authors: Ursula G Falkmer; Thomas Gustafsson; Ralf Wenzel; Nils Wierup; Frank Sundler; Harshad Kulkarni; Richard P Baum; Sture E Falkmer Journal: Ups J Med Sci Date: 2015-06-20 Impact factor: 2.384
Authors: Anya Medina; Saba Parween; Sara Ullsten; Neelanjan Vishnu; Yuk Ting Siu; My Quach; Hedvig Bennet; Alexander Balhuizen; Lina Åkesson; Nils Wierup; Per Ola Carlsson; Ulf Ahlgren; Åke Lernmark; Malin Fex Journal: Diabetologia Date: 2017-12-06 Impact factor: 10.122