Elevated cocaine- and amphetamine-regulated transcript immunoreactivity in the circulation of patients with neuroendocrine malignancy.
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.
Bech
Paul
P
Department of Metabolic Medicine, Hammersmith Hospital, Commonwealth Building, 6th Floor, Imperial College London, London W12 0NN, United Kingdom. sbloom@ic.ac.uk
Winstanley
Virginia
V
Murphy
Kevin G
KG
Sam
Amir H
AH
Meeran
Karim
K
Ghatei
Mohammad A
MA
Bloom
Stephen R
SR
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
D053379:Chromogranin A; D053378:Chromogranin B; D009419:Nerve Tissue Proteins; D000098882:Cocaine- and Amphetamine-Regulated Transcript Protein