title: Elevated cocaine- and amphetamine-regulated transcript immunoreactivity in the circulation of patients with neuroendocrine malignancy.
abstract: BACKGROUND
  Cocaine- and amphetamine-regulated transcript (CART) codes for a peptide widely distributed in nervous and endocrine tissues. CART immunoreactivity (CART-LI) has been detected in human insulinomas.
  
  
  OBJECTIVE
  The objective of the study was to investigate the measurement of plasma CART-LI as a tumor marker of neuroendocrine malignancy.
  
  
  METHODS
  Plasma CART-LI levels were measured in 401 patients with a range of diagnoses: neuroendocrine malignancy (n = 131), after removal of neuroendocrine malignancy (n = 27), without any form of tumor or renal impairment (n = 192), with renal impairment (n = 17) and with nonneuroendocrine tumors (n = 34). Chromatography methods were used to investigate CART-LI circulating in human plasma.
  
  
  RESULTS
  The upper limit of normal calculated for CART-LI was 150 pmol/liter. Mean circulating plasma CART-LI among neuroendocrine tumor patients was 440 pmol/liter, 56% of subjects having levels greater than 150 pmol/liter. Measuring CART-LI in addition to chromogranin (Cg)-A improved the sensitivity for neuroendocrine malignancy from 85 to 91%, whereas combined use of CgA and CgB had a joint sensitivity of 89%. Of 38 patients with pancreatic neuroendocrine tumors, 71% had plasma CART-LI levels greater than 150 pmol/liter, increasing to 95% in those classified with progressive disease (n = 20, mean CART-LI 625 pmol/liter), compared with 80% for CgA. Chromatographic analysis suggests that circulating CART-LI is present as one major form, which may correspond to CART (62-102) or another unknown form.
  
  
  CONCLUSIONS
  We demonstrate CART-LI as a specific tumor marker in patients with a range of neuroendocrine tumors. Used in combination with CgA, CART-LI measurement has the potential to improve sensitivity in diagnosis and follow-up of neuroendocrine tumors, in particular progressive pancreatic neuroendocrine tumors.
authors.affiliation: Department of Metabolic Medicine, Hammersmith Hospital, Commonwealth Building, 6th Floor, Imperial College London, London W12 0NN, United Kingdom. sbloom@ic.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Bech
authors.forename: Virginia
authors.initials: V
authors.lastname: Winstanley
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Murphy
authors.forename: Amir H
authors.initials: AH
authors.lastname: Sam
authors.forename: Karim
authors.initials: K
authors.lastname: Meeran
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
mesh_terms: D000328:Adult; D018278:Carcinoma, Neuroendocrine / Q000097:blood* / Q000175:diagnosis; D002845:Chromatography; D053379:Chromogranin A / Q000097:blood; D053378:Chromogranin B / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000097:blood*; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein
chemical_list: D053379:Chromogranin A; D053378:Chromogranin B; D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein