期刊
NEUROENDOCRINOLOGY
卷 94, 期 3, 页码 228-236出版社
KARGER
DOI: 10.1159/000329044
关键词
Cocaine- and amphetamine-regulated transcript; Neuroendocrine tumors; Endocrine pancreatic tumors; Gastrointestinal tract; Medullary thyroid carcinomas; Regulatory peptides
资金
- Swedish Research Council [522-2008-4216, K2009-55X 21111-01-4, K2007-55X-04499-33-3]
- Faculty of Medicine at Lund University
- Royal Physiographic Society in Lund
- Futurum - Academy for Healthcare at the Jonkoping County Council
- Foundation for Clinical Cancer Research in Jonkoping
- Novo Nordisk
- Gyllenstiernska Krapperup Foundation
- Swedish Society of Medicine Foundation
- Fredrik Foundation
- Ingrid Thuring Foundation
- Magnus Bergwall Foundation
- Albert Pahlsson Foundation
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. Copyright (C) 2011 S. Karger AG, Basel
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