Chromogranin A Radioimmunoassay

Chromogranins and secretogranins constitute a family of uniquely acidic proteins that are co-stored with neurotransmitters and peptide hormones in the brain and the diffuse neuroendocrine system (Winkler, H. & Fischer-Colbrie, R.1992). Structurally these proteins are products of different genes but share some overall properties such as an abundance of acidic amino acid residues and several pairs of basic amino acids as potential positions for post-translational cleavage. Chromogranins are co-stored and co-released with neuropeptides and hormones in the neuroendocrine cells throughout the body. A role for chromogranins in the generation of hormonal granules and package of hormones has been suggested. Furthermore, chromogranins can be cleaved into smaller fragments, which can display biological activities such as inhibition of hormonal release, vasodilatation and anti-microbiological effects. Tumours of neuroendocrine origin usually present with increased plasma levels of chromogranin A. The neuroendocrine tumours are derived from the neuroendocrine cells and typical neuroendocrine tumours are carcinoid tumours, pheochromocytomas, neuroblastomas, small cell lung cancers, hyperparathyroid adenomas, pituitary tumours, prostate cancers and pancreatic islet tumours and including the MEN1 and MEN2 syndromes. This also includes the different neuroendocrine tumour syndromes, namely the gastrinomas, insulinomas, glucagonomas, somatostatinomas. PPomas and the non-functioning neuroendocrine tumours (Eriksson, B. et al. 2000). For these tumours, chromogranin A has been shown to be the best circulating marker (Bajetta, E. et al. 1999). The first radioimmunoassay for measurements of chromogranin A was introduced in 1986 (O’Connor, D.T. & Deftos, L.J. 1986). Since then other assays for measurements of intact human chromogranin A have been reported. Assays for measurements of defined regions of chromogranin A have also been established, such as specific methods for pancreastatin and other regions of chromogranin A (Stridsberg, M. 2000). The present chromogranin A is a competitive method based on polyclonal antibodies raised in rabbits. The antibodies were raised against a purified fragment containing amino acid sequence 116-439 in the chromogranin A molecule and it has been shown to measure both intact chromogranin A and fragments of chromogranin A (Stridsberg, M. et al. 1993, Stridsberg, M. et al. 1995).