Chromogranin A

Serum

0.5 mL

0.3 mL (Note: This volume does not allow for repeat testing.)

Gel-barrier tube

An aid in the detection and monitoring of neuroendocrine cancers including pheochromocytomas, medullary thyroid carcinomas, functioning and nonfunctioning islet cell and gastrointestinal amine precursor uptake and decarboxylation tumors, and pituitary adenomas. A possible adjunct in outcome prediction and follow-up in advanced prostate cancer.

Elevated CGA levels may be seen in non-NEN malignancies including hepatocellular carcinoma⁴¹ and breast cancer.⁴²

Circulating CgA is increased in several common, non-neoplastic conditions associated with tissue damage and remolding.^5,43-46 These include:

• Gastrointestinal disorders such as chronic atrophic gastritis, Helicobacter pylori infection, liver cirrhosis, chronic hepatitis, pancreatitis, inflammatory bowel diseases and irritable bowel syndrome.

• Cardiovascular disorders such as hypertension, chronic heart failure, acute coronary syndromes.

• Rheumatoid diseases such as giant cell arteritis, rheumatoid arthritis, systemic lupus erythematosus and pulmonary obstructive disease.

• Kidney and liver functional impairment ostensibly due to reduced clearance.⁵

• Endocrine disorders of non-neuroendocrine nature, such as hyperthyroidism, likely due to enhanced sympathetic activity which pairs with attenuation of the vagal tone.

Chronic use of proton pump inhibitors can produce CGA elevations, often to many times above the normal range.^5,47

Sensitivity of circulating CgA is a relatively poor marker for poorly differentiated NETs.^5,43 The level of circulation CgA is often normal in patients with localized, non-functional (non-secretory) NETs, such as those of the appendix, pancreas, lungs, duodenum and rectum.⁵

CgA may not be increased in patients with multiple endocrine neoplasia type 1(MEN).⁵

As with all immunometric assays there is a low, but definite, possibility of false-positive results in patients with heterophile antibodies.

The Thermofisher/BRAHMS KRYPTOR® assay employs Time-Resolved Amplified Cryptate Emission Cryptate Emission (TRACE) technology based on a non-radioactive energy transfer between a donor (europium cryptate) and an acceptor (XL665) in a sandwich immunofluorescent format using two mouse monoclonal antibodies.^37-40 This assay is calibrated against recombinant human CG, and according to the manufacturer's package insert.¹

0.0 – 101.8 ng/mL

Chromogranin A¹ is a hydrophilic glycoprotein that is stored in the chromaffin granules of the neuroendocrine cells.² The physiologic role of CgA has not been fully elucidated, but studies suggest that it serves as a precursor to other biologically active peptides and facilitates the production of other hormones and neuropeptides.^2-4 In healthy individuals, most of the CgA found in the circulation is derived from enterocromaffin- like (ECL) cells⁵ found in the gastric glands of the stomach in the vicinity of parietal cells. ECL cells serve to stimulate the production of gastric acid via the neuroendocrine release of histamine.⁵

Neuroendocrine cells receive neuronal input that stimulates them to release a variety of molecules (in many cases including CgA). Neuroendocrine cells are ubiquitous throughout the body and can be found in numerous organs including the gastrointestinal (GI) tract (in the small intestine, rectum, stomach, colon, esophagus and appendix), the gallbladder, the pancreas (islet cells) and the thyroid (C cells). Neuroendocrine cells are also found in the lungs and airways into the lungs (bronchi), as well as the respiratory tract of the head and neck. The pituitary gland, the parathyroid glands and the inner layer of the adrenal gland (adrenal medulla) are largely made up of neuroendocrine cells. Other locations of neuroendocrine cells include the thymus, kidneys, liver, prostate, skin, cervix, ovaries and testicles.

Neuroendocrine neoplasms (NENs) can originate from any of the neuroendocrine cells that are scattered throughout the body. Because many NENs are secretory, the measurement of circulating biomarkers can be helpful for their diagnosis as well as for estimating tumor burden, assessing tumor response to treatment, monitoring disease progression, and predicting outcomes.^5-19 Patients with well-differentiated NENs frequently express elevated blood levels of CgA. Numerous studies have documented the utility of measuring circulating CgA levels in patients with a variety of NENs, including carcinoids,²¹ tumors of the gastroenteropancreatic tract,^{5,15,20,24-26} pheochromocytomas,^22,23 neuroblastomas,²⁷ islet cell tumors,^16,28 and other amine precursor uptake and decarboxylation (APUD) tumors.^15,29,30 CGA can be elevated in patients with multiple endocrine neoplasia, type 1 (MEN1) and is used for the routine surveillance of this condition.^31,32

Prostate cancers often contain cells with partial neuroendocrine differentiation. The value of CgA as a biomarker of prostate cancer has been extensively evaluated with several studies suggesting that it has prognostic utility in certain cases, such as in combination with NSE assessment or in patients treated with certain specific therapies.^33-36