title: Chromogranin A--biological function and clinical utility in neuro endocrine tumor disease.
abstract: BACKGROUND
  Neuroendocrine tumors (NETs) are a form of cancer that differ from other neoplasia in that they synthesize, store, and secrete peptides, e.g., chromogranin A (CgA) and amines. A critical issue is late diagnosis due to failure to identify symptoms or to establish the biochemical diagnosis. We review here the utility of CgA measurement in NETs and describe its biological role and the clinical value of its measurement.
  
  
  METHODS
  Literature review and analysis of the utility of plasma/serum CgA measurements in NETs and other diseases.
  
  
  RESULTS
  CgA is a member of the chromogranin family; its transcription and peptide processing are well characterized, but its precise function remains unknown. Levels are detectable in the circulation but vary substantially (approximately 25%) depending on which assay is used. Serum and plasma measurements are concordant. CgA is elevated in approximately 90% of gut NETs and correlates with tumor burden and recurrence. Highest values are noted in ileal NETs and gastrointestinal NETs associated with multiple endocrine neoplasia type 1. Both functioning and nonfunctioning pancreatic NETs have elevated values. CgA is more frequently elevated in well-differentiated tumors compared to poorly differentiated NETs. Effective treatment is often associated with decrease in CgA levels. Proton pump inhibitors falsely increase CgA, but levels normalize with therapy cessation.
  
  
  CONCLUSIONS
  CgA is currently the best available biomarker for the diagnosis of NETs. It is critical to establish diagnosis and has some utility in predicting disease recurrence, outcome, and efficacy of therapy. Measurement of plasma CgA is mandatory for the effective diagnosis and management of NET disease.
authors.affiliation: Gastrointestinal Pathobiology Research Group, Yale University School of Medicine, New Haven, CT, USA. imodlin@optonline.net
authors.forename: Irvin M
authors.initials: IM
authors.lastname: Modlin
authors.forename: Bjorn I
authors.initials: BI
authors.lastname: Gustafsson
authors.forename: Steven F
authors.initials: SF
authors.lastname: Moss
authors.forename: Marianne
authors.initials: M
authors.lastname: Pavel
authors.forename: Apostolos V
authors.initials: AV
authors.lastname: Tsolakis
authors.forename: Mark
authors.initials: M
authors.lastname: Kidd
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D053379:Chromogranin A / Q000097:blood*; D006801:Humans; D018358:Neuroendocrine Tumors / Q000097:blood* / Q000175:diagnosis*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D053379:Chromogranin A