Comparison of the utility of Cocaine- and Amphetamine-Regulated Transcript (CART), chromogranin A, and chromogranin B in neuroendocrine tumor diagnosis and assessment of disease progression.

CONTEXT Prognosis in patients with neuroendocrine tumors (NETs) is often poor, frequently reflecting delayed diagnosis. Hence, accurate and practical NET markers are needed. Cocaine- and amphetamine-regulated transcript (CART) peptide is a potential novel NET marker. DESIGN AND PARTICIPANTS Circulating levels of CART peptide and the established NET markers chromogranin A (CgA) and chromogranin B (CgB) were measured using RIA in 353 patients with NET (normal renal function) and in controls. Clinical data were collected retrospectively. MAIN OUTCOME MEASURE(S) The comparative and combined utility of CART, CgA, and CgB for diagnosis and assessment of disease progression was measured in different NET subtypes. RESULTS CgA and CgB in combination improved diagnostic accuracy in patients with gut NETs, nongastroenteropancreatic NETs, and NETs with an unknown primary origin compared with each biomarker alone. Measuring CART did not further improve diagnosis in these NET subtypes. For pancreatic NETs, CgB was superior to CgA and CART in detecting stable disease (P < .007), whereas CgA and CART in combination were most effective in identifying progressive disease. In phaeochromocytomas/paragangliomas (PCC/PGL), CART was the most useful biomarker for identifying stable (P < .001) and progressive (P = .001) disease. Consistent with this, plasma CART decreased following PCC/PGL tumor resection, remaining low in all patients in remission, but increasing in those with progressive disease. CONCLUSIONS CART is a useful marker for identifying progressive pancreatic NETs. CART is superior to CgA and CgB in detecting stable and progressive PCC/PGLs, and may have a role as a surveillance marker for PCC/PGL patients.

[1]  G. Eisenhofer,et al.  Laboratory evaluation of pheochromocytoma and paraganglioma. , 2014, Clinical chemistry.

[2]  P. Ruszniewski,et al.  Lanreotide in metastatic enteropancreatic neuroendocrine tumors. , 2014, The New England journal of medicine.

[3]  K. Pacak,et al.  Clinical utility of chromogranin A in SDHx‐related paragangliomas , 2014, European journal of clinical investigation.

[4]  S. Bloom,et al.  The biochemical utility of chromogranin A, chromogranin B and cocaine- and amphetamine-regulated transcript for neuroendocrine neoplasia , 2014, Annals of clinical biochemistry.

[5]  O. Dekkers,et al.  Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 patients. , 2013, The Journal of clinical endocrinology and metabolism.

[6]  M. Saif,et al.  Biomarkers in neuroendocrine tumors. , 2013, JOP : Journal of the pancreas.

[7]  E. Baudin,et al.  Rare neuroendocrine tumours: results of the surveillance of rare cancers in Europe project. , 2013, European journal of cancer.

[8]  Mohid S. Khan,et al.  Improving the Diagnosis and Management of Neuroendocrine Tumors: Utilizing New Advances in Biomarker and Molecular Imaging Science , 2013, Neuroendocrinology.

[9]  I. Drozdov,et al.  The Identification of Gut Neuroendocrine Tumor Disease by Multiple Synchronous Transcript Analysis in Blood , 2013, PloS one.

[10]  J. Ryu,et al.  Clinical Usefulness of Plasma Chromogranin A in Pancreatic Neuroendocrine Neoplasm , 2013, Journal of Korean medical science.

[11]  T. Fujimori,et al.  Clinical validation of the gastrointestinal NET grading system: Ki67 index criteria of the WHO 2010 classification is appropriate to predict metastasis or recurrence , 2013, Diagnostic Pathology.

[12]  RyanA . Stevenson,et al.  Prognostic and predictive biomarkers in gastroenteropancreatic neuroendocrine tumors. , 2013, JOP : Journal of the pancreas.

[13]  Yihong Yang,et al.  CART peptide induces neuroregeneration in stroke rats , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[14]  S. Petersenn,et al.  Plasma and Urinary Metanephrines Determined by an Enzyme Immunoassay, but not Serum Chromogranin A for the Diagnosis of Pheochromocytoma in Patients with Adrenal Mass , 2012, Experimental and Clinical Endocrinology & Diabetes (Barth).

[15]  N. Martin,et al.  Improved diagnostic accuracy for neuroendocrine neoplasms using two chromogranin A assays , 2012, Clinical endocrinology.

[16]  N. Martin,et al.  Quantifying the effects of renal impairment on plasma concentrations of the neuroendocrine neoplasia biomarkers chromogranin A, chromogranin B, and cocaine- and amphetamine-regulated transcript. , 2012, Clinical chemistry.

[17]  K. Herrmann,et al.  Chromogranin A as Serum Marker for Gastroenteropancreatic Neuroendocrine Tumors: A Single Center Experience and Literature Review , 2012, Cancers.

[18]  P. Söderkvist,et al.  Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas. , 2011, Endocrine-related cancer.

[19]  James C Yao,et al.  Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. , 2011, The Journal of clinical endocrinology and metabolism.

[20]  F. Sundler,et al.  Cocaine- and Amphetamine-Regulated Transcript in Neuroendocrine Tumors , 2011, Neuroendocrinology.

[21]  Laura H. Tang,et al.  Effect of Tumor Heterogeneity on the Assessment of Ki67 Labeling Index in Well-differentiated Neuroendocrine Tumors Metastatic to the Liver: Implications for Prognostic Stratification , 2011, The American journal of surgical pathology.

[22]  E. D. de Vries,et al.  Everolimus for advanced pancreatic neuroendocrine tumors. , 2011, The New England journal of medicine.

[23]  S. Bornstein,et al.  Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma. , 2010, Endocrine-related cancer.

[24]  D. Coppola,et al.  The Pathologic Classification of Neuroendocrine Tumors: A Review of Nomenclature, Grading, and Staging Systems , 2010, Pancreas.

[25]  G. Mamikunian,et al.  Development of a Highly Sensitive and Specific Carboxy-Terminal Human Pancreastatin Assay to Monitor Neuroendocrine Tumor Behavior , 2010, Pancreas.

[26]  D. Berney,et al.  Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours. , 2009, Endocrine-related cancer.

[27]  K. Öberg Genetics and molecular pathology of neuroendocrine gastrointestinal and pancreatic tumors (gastroenteropancreatic neuroendocrine tumors) , 2009 .

[28]  L. Liotta,et al.  National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice: quality requirements. , 2008, Clinical chemistry.

[29]  Manal M. Hassan,et al.  One hundred years after "carcinoid": epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  S. Bloom,et al.  Elevated cocaine- and amphetamine-regulated transcript immunoreactivity in the circulation of patients with neuroendocrine malignancy. , 2008, The Journal of clinical endocrinology and metabolism.

[31]  A. Scarpa,et al.  TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system , 2007, Virchows Archiv.

[32]  F. D. De Braud,et al.  Chromogranin A as a marker of neuroendocrine neoplasia: an Italian Multicenter Study. , 2007, Endocrine-related cancer.

[33]  E. Šloncová,et al.  Cocaine- and amphetamine-regulated transcript (CART) peptide specific binding in pheochromocytoma cells PC12. , 2007, European journal of pharmacology.

[34]  M. Stridsberg,et al.  Measurements of chromogranin B can serve as a complement to chromogranin A , 2007, Regulatory Peptides.

[35]  M. Bloomston,et al.  Hepatic Artery Chemoembolization in 122 Patients with Metastatic Carcinoid Tumor: Lessons Learned , 2007, Journal of Gastrointestinal Surgery.

[36]  M. Boniardi,et al.  The role of chromogranin A in the management of patients with phaeochromocytoma , 2006, Clinical endocrinology.

[37]  F. Sundler,et al.  CART is a novel islet regulatory peptide , 2006, Peptides.

[38]  E. Eisenhauer,et al.  RECIST revisited: a review of validation studies on tumour assessment. , 2006, European journal of cancer.

[39]  D. Goldstein,et al.  Biochemical and clinical manifestations of dopamine-producing paragangliomas: utility of plasma methoxytyramine. , 2005, The Journal of clinical endocrinology and metabolism.

[40]  D. Conte,et al.  Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids. , 2005, European journal of endocrinology.

[41]  R. Cianci,et al.  High Plasma Levels of Human Chromogranin a and Adrenomedullin in Patients with Pheochromocytoma , 2005, Tumori.

[42]  S. Bloom,et al.  Regulation of rat pituitary cocaine- and amphetamine-regulated transcript (CART) by CRH and glucocorticoids. , 2004, American journal of physiology. Endocrinology and metabolism.

[43]  P. Bossuyt,et al.  The diagnostic odds ratio: a single indicator of test performance. , 2003, Journal of clinical epidemiology.

[44]  K. Calhoun,et al.  Serum peptide profiles in patients with carcinoid tumors. , 2003, American journal of surgery.

[45]  I. Modlin,et al.  A 5‐decade analysis of 13,715 carcinoid tumors , 2003, Cancer.

[46]  E. Baudin,et al.  Chromogranin A and the α -subunit of glycoprotein hormones in medullary thyroid carcinoma and phaeochromocytoma , 2001, British Journal of Cancer.

[47]  J. Holst,et al.  The hypothalamic satiety peptide CART is expressed in anorectic and non‐anorectic pancreatic islet tumors and in the normal islet of Langerhans , 1999, FEBS letters.

[48]  M. Stridsberg,et al.  Chromogranin A and pancreastatin-like immunoreactivity in normal pregnancies. , 1996, The Journal of clinical endocrinology and metabolism.

[49]  P. Couceyro,et al.  PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[50]  L. Kvols,et al.  New Molecular Aspects for the Diagnosis and Treatment of Neuroendocrine Gastroenteropancreatic Tumors , 1994, Annals of the New York Academy of Sciences.

[51]  J. Polak,et al.  Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value. , 1989, The Journal of clinical investigation.

[52]  J. Rehfeld,et al.  Chromogranin A as a biomarker in cardiovascular disease. , 2014, Biomarkers in medicine.

[53]  M. Colombo,et al.  Chromogranin A levels in chronic liver disease and hepatocellular carcinoma. , 2009, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[54]  R. Jensen,et al.  Gastroenteropancreatic neuroendocrine tumours. , 2008, The Lancet. Oncology.

[55]  R. Bílek,et al.  Chromogranin A, a member of neuroendocrine secretory proteins as a selective marker for laboratory diagnosis of pheochromocytoma. , 2008, Physiological research.

[56]  A. Worster,et al.  Understanding receiver operating characteristic (ROC) curves. , 2006, CJEM.

[57]  L. Aaltonen,et al.  Pathology and genetics of tumours of the digestive system , 2000 .

[58]  M. Stridsberg,et al.  Chromogranin A and chromogranin B are sensitive circulating markers for phaeochromocytoma. , 1997, European journal of endocrinology.

[59]  P. Scriba,et al.  Experiences Using Chloramine-T and 1, 3, 4, 6-Tetrachloro-3α, 6α-diphenylglycoluril (lodogen®) for Radioiodination of Materials for Radioimmunoassay , 1981 .