The biochemical utility of chromogranin A, chromogranin B and cocaine- and amphetamine-regulated transcript for neuroendocrine neoplasia

Neuroendocrine neoplasia (NEN) is a heterogeneous group of tumours and often represents a therapeutic challenge to clinicians. The peptides chromogranin A (CgA), chromogranin B (CgB) and cocaine-and amphetamine-regulated transcript (CART) are widely distributed throughout the neuroendocrine system. CgA and CgB have been used as general NEN biomarkers for many years, while CART has only recently been identified. Of these biomarkers, CgA is the most commonly used. However, circulating CgA concentrations exhibit considerable intra-individual biological variation, are altered by proton pump inhibitors (PPIs) and somatostatin analogues and are elevated in non-NEN malignancies. Therefore, interpretation of CgA results must be in the context of these confounding factors. The effects of treatment and non-NEN conditions on circulating CgB and CART concentrations are less well understood. CgB is less affected by impaired renal function and PPIs than CgA; while, circulating CART concentrations lack a diurnal variation in humans and are more reliable markers of pancreatic NEN malignancy than CgA. The utility of circulating CgA measurements in NEN prognosis, surveillance and disease recurrence has been widely investigated. However, the utility of CgB and CART in NEN management is yet to be elucidated. Further studies are needed to establish whether CgB and CART are useful alternatives to CgA.