title: Cocaine- and amphetamine-regulated transcript in neuroendocrine tumors.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Surgery, Ryhov Hospital, Jönköping, Sweden.
authors.forename: Kalle
authors.initials: K
authors.lastname: Landerholm
authors.forename: Sture E
authors.initials: SE
authors.lastname: Falkmer
authors.forename: Johannes
authors.initials: J
authors.lastname: Järhult
authors.forename: Frank
authors.initials: F
authors.lastname: Sundler
authors.forename: Nils
authors.initials: N
authors.lastname: Wierup
mesh_terms: D002276:Carcinoid Tumor / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine; D005770:Gastrointestinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D060787:Neoplasm Grading; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein