Chromogranin A

Chromogranin A is a secretory protein, composed of 439 amino acids, found in the large dense-core vesicles of the neuroendocrine cells. It belongs to the family of granins that includes chromogranin B, chromogranin C, and secretogranin II.

Chromogranin A can be either measured in the serum or detected by immunohistochemistry in a tissue specimen.

Normal findings

Chromogranin A (blood test): ≤225 ng/mL ^[1]

However, the reference ranges for serum chromogranin A vary widely with the techniques used.

A wide variety of neuroendocrine tumors stain positive for chromogranin A.

Gastro-entero-pancreatic neuroendocrine tumors that stain positive for chromogranin A are as follows ^{[2, 3]} :

• Carcinoid tumor

• Gastrinoma

• Insulinoma

• Glucagonoma

• VIPoma

• Somatostatinoma

Thyroid/parathyroid tumors that stain positive for chromogranin A are as follows:

• Medullary thyroid cancer

• Parathyroid tumors

Nervous system tumors that stain positive for chromogranin A are as follows:

• Ganglioneuroma

• Ganglioneuroblastoma

• Neuroblastoma

• Medulloblastoma

Adrenal system tumors that stain positive for chromogranin A include pheochromocytoma. Lung tumors include small cell cancer.

Elevation in serum CgA correlates with the size, extension and the histopathology of the neuroendocrine tumors; it is usually higher in large, metastatic, and well-differentiated tumors. Elevation is mainly detected in the following:

• Carcinoid tumors

• Pheochromocytoma

• Medullary thyroid cancer

• Small cell lung cancer (sometimes)

CgA can also be elevated in prostate adenocarcinoma. Serum chromogranin A can be elevated in other situations and conditions, including chronic proton-pump inhibitors use, renal failure, liver failure, heart failure, rheumatoid arthritis, inflammatory bowel disease, and hypertension.

See the list below:

• Patient instruction: No need for fasting

• Collection tube: Red top tube or gel-barrier tube

• Unacceptable Conditions: Grossly hemolyzed specimens

• Specimen Preparation: Separate serum from cells and transfer to transport tube.

• Storage/Transport Temperature: Refrigerated or frozen

• Stability : 2 weeks (refrigerated); 6 weeks (frozen)

• Panels: None

Description

Chromogranin A (CgA) is a secretory protein, composed of 439 amino acids, found in the large dense-core vesicles of the neuroendocrine cells. It belongs to the family of granins that includes chromogranin B, chromogranin C, and secretogranin II. Chromogranin A contains multiple cleavage sites, which undergo a tissue-specific proteolytic process, leading to the production of many biologically active peptides including vasostatin I, vasostatin II, pancreastatin, catestatin, parastatin, and serpinin. ^{[4, 5, 6, 7]}

CgA is co-stored with a tissue-specific peptide hormone or neuropeptide and exerts an autocrine and paracrine effect on secretory activity of the neuroendocrine cells. Cumulative evidences suggest that CgA’s derived peptides are involved in a wide range of activities, like regulation of blood pressure (catestatin), glucose metabolism (pancreastatin, catestatin), neuroprotection (serpinin), and tumor angiogenesis (vasostatin I, vasostatin II).

Indications/Applications

Chromogranin A can be used, in conjunction with other testing modalities, as a diagnostic tool, but caution is advised since it is elevated in many other conditions. However, chromogranin A might have some prognostic significance.

Serum CgA can be used to monitor neuroendocrine tumor progression after a surgical intervention as well as medical therapy, with the only exception being somatostatin analogs that inhibit tumor secretion rather than causing tumor reduction. Serum CgA should be measured at the same laboratory using the same technique, since the test is still not standardized. ^[8]