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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.
Results for this test are designated to be for research purposes only by the manufacturer. The performance characteristics of this product have not been established. Results for this test should not be used as absolute evidence of presence or absence of malignant disease without confirmation of the diagnosis by another medically established diagnostic product or procedure. Values obtained with different assay methods or kits cannot be used interchangeably. Results cannot be interpreted as absolute evidence of the presence or absence of malignant disease.
Elevated CGA levels may be seen in non-NEN malignancies including hepatocellular carcinoma 41 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.
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
1. BRAHMS CgA II KRYPTOR® IFU-839R-USA [package insert]. Middletown, VA: Fisher Scientific Company LLC; 2015.
2. Borges R, Daz-Vera J, Domnguez N, Arnau MR, Machado JD. Chromogranins as regulators of exocytosis. J Neurochem. 2010 Jul;114(2):335-343. PubMed 20456013
3. D'amico MA, Ghinassi B, Izzicupo P, Manzoli L, Di Baldassarre A. Biological function and clinical relevance of chromogranin A and derived peptides. Endocr Connect. 2014 Apr 29;3(2):R45-54. PubMed 24671122
4. Bartolomucci A, Possenti R, Mahata SK, Fischer-Colbrie R, Loh YP, Salton SR. The extended granin family: structure, function, and biomedical implications. Endocr Rev. 2011 Dec;32:755-797. PubMed 21862681
5. Ardill JE, O'Dorisio TM. Circulating biomarkers in neuroendocrine tumors of the enteropancreatic tract: application to diagnosis, monitoring disease, and as prognostic indicators. Endocrinol Metab Clin North Am. 2010 Dec;39(4):777-790. PubMed 21095544
6. Strosberg JR, Halfdanarson TR, Bellizzi AM, et al. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors. Pancreas. 2017 Jul;46(6):707-714. PubMed 28609356
7. Citterio D, Pusceddu S, Facciorusso A, et al. Primary tumour resection may improve survival in functional well-differentiated neuroendocrine tumours metastatic to the liver. Eur J Surg Oncol. 2017 Feb;43(2):380-387. PubMed 27956320
8. Gut P, Czarnywojtek A, Fischbach J, et al. Chromogranin A - unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls. Arch Med Sci. 2016 Feb 1;12(1):1-9. PubMed 26925113
9. Yao JC, Pavel M, Lombard-Bohas C, et al. Everolimus for the treatment of advanced pancreatic neuroendocrine tumors: Overall survival and circulating biomarkers from the randomized, Phase III RADIANT-3 Study. J Clin Oncol. 2016 Nov 10;34(32):3906-3913. PubMed 27621394
10. Yang X, Yang Y, Li Z, et al. Diagnostic value of circulating chromogranin a for neuroendocrine tumors: A systematic review and meta-analysis. PLoS One. 2015 2015 Apr 20;10(4):e0124884. PubMed 25
