Clinical Information

Chromogranin A (CgA) is a 439-amino acid protein with a molecular weight of 48 to 60 kDa, depending on glycosylation and phosphorylation status. It is a member of the granin family of proteins and polypeptides. Granins are widespread in endocrine, neuroendocrine, peripheral, and central nervous tissues, where they are found in secretory granules alongside the tissue-specific secretion products. The role of granins within the granules is to maintain the regulated secretion of these signaling molecules. This includes:

-Facilitating the formation of secretory granules

-Calcium- and pH-mediated sequestration and re-solubilization of hormones or neurotransmitters

-Regulation of neuropeptide and peptide hormone processing through modulation of prohormone convertase activity

In addition, granins contain multiple protease and peptidase cleavage sites and, upon intra- or extracellular cleavage, give rise to a series of peptides with distinct extracellular functions. Some of these have defined functions, such as pancreastatin, vasostatin, and catestatin, while others are less well characterized.(1)

Because of its ubiquitous distribution within neuroendocrine tissues, CgA can be a useful diagnostic marker for neuroendocrine neoplasms, including carcinoids, pheochromocytomas, neuroblastomas, medullary thyroid carcinomas, some pituitary tumors, functioning and nonfunctioning islet cell tumors, and other amine precursor uptake and decarboxylation tumors. It can also serve as a sensitive means for detecting residual or recurrent disease in treated patients.(2-4)

Carcinoid tumors in particular almost always secrete CgA along with a variety of specific modified amines, chiefly serotonin (5-hydroxytryptamine) and peptides.(1-4) Carcinoid tumors are subdivided into foregut carcinoids, arising from respiratory tract, stomach, pancreas or duodenum (approximately 15% of cases); midgut carcinoids, occurring within jejunum, ileum, or appendix (approximately 70% of cases); and hindgut carcinoids, which are found in the colon or rectum (approximately 15% of cases). Serum CgA and urine 5-hydroxyindolacetic acid (5-HIAA) are considered the most useful biochemical markers and are first-line tests in disease surveillance of most patients with carcinoid tumors.(2-4) Serum CgA measurements have been used in conjunction with, or alternative to, measurements of serum or whole blood serotonin, urine serotonin and 5-HIAA, and imaging studies in the differential diagnosis of isolated symptoms suggestive of carcinoid syndrome, in particular, flushing.

A number of tumors that are not derived from classical endocrine or neuroendocrine tissues but contain cells with partial neuroendocrine differentiation, such as small-cell carcinoma of the lung or prostate carcinoma, may also display elevated CgA levels. However, the role of CgA measurement is not well defined in these tumors.