Chromogranin A

"When chromogranin A comes back elevated, it is not proof positive that you have a neuroendocrine tumor... but it's still a useful test." —Dr Larry Kvols

A biomarker with utility in different NET types

Despite certain limitations, chromogranin A (CgA) is currently the most useful circulating marker for GEP-NETs.1,2 It is elevated in the blood levels of up to 90% of patients with NETs,2,3 with levels that are independent of hormone secretion.3,4 CgA levels have prognostic significance, and they can be used to help monitor disease progression, as suggested by the NCCN guidelines. CgA levels have also been correlated with tumor burden and reduced survival.5,6

"The reason that we don't refer to tumors producing chromogranin A as 'functional' is that it's a tumor marker only. It's not associated with a syndrome." —Dr Larry Kvols

Although CgA is a reliable general tumor marker, other biomarker tests may be a useful complement for diagnosing pancreatic NETs. Different types of functional pancreatic NETs are associated with syndromes caused by the production of specific hormones and amines. Tests for these biochemical substances can help pinpoint the presence and type of a pancreatic NET.7,8

The best overall combination of sensitivity and specificity of any known circulating NET biomarker9,10

CgA testing is available through most hospitals and commercial pathology labs

Several commercially available assays measure CgA levels.11

NOTE: When administering CgA tests, clinicians should keep in mind that tests are not standardized.11 Results may vary among laboratories and assays.11 Certain therapies can increase CgA levels without the presence of a NET, notably proton pump inhibitors.1,10 Some conditions can also increase CgA levels—chronic atrophic gastritis, renal or hepatic failure, and arterial hypertension, for example.1

For diagnostic accuracy—as well as continued disease management—preliminary biomarker results should be confirmed with diagnostic imaging and/or endoscopic techniques, along with biopsy when appropriate.17

1. Ferolla P, Faggiano A, Mansueto G, et al. The biological characterization of neuroendocrine tumors: the role of neuroendocrine markers. J Endocrinol Invest. 2008;31(3):277-286.
2. Öberg K. Biochemical diagnosis of neuroendocrine GEP tumor. Yale J Biol Med. 1997;70(5-6):501-508.
3. Peracchi M, Conte D, Gebbia C, et al. Plasma chromogranin A in patients with sporadic gastro-entero-pancreatic neuroendocrine tumors or multiple endocrine neoplasia type 1. Eur J Endocrinol. 2003;148(1):39-43.
4. Sobol RE, Memoli V, Deftos LJ. Hormone-negative, chromogranin A-positive endocrine tumors. N Engl J Med. 1989;320(7):444-447.
5. Janson ET, Holmberg L, Stridsberg M, et al. Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center. Ann Oncol. 1997;8(7):685-690.
6. Korse CM, Bonfrer JMG, Aaronson NK, Hart AAM, Taal BG. Chromogranin A as an alternative to 5-hydroxyindoleacetic acid in the evaluation of symptoms during treatment of patients with neuroendocrine tumors. Neuroendocrinology. 2009;89(3):296-301.
7. Vinik AI, Silva MP, Woltering EA, Go VLW, Warner R, Caplin M. Biochemical testing for neuroendocrine tumors. Pancreas. 2009;38(8):876-889.
8. Modlin IM, Öberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9(1):61-72.
9. Campana D, Nori F, Piscitelli L, et al. Chromogranin A: is it a useful marker of neuroendocrine tumors? J Clin Oncol. 2007;25(15):1967-1973.
10. Eriksson B, Öberg K, Stridsberg M. Tumor markers in neuroendocrine tumors. Digestion. 2000;62(suppl 1):33-38.
11. Stridsberg M, Eriksson B, Öberg K, Janson ET. A comparison between three commercial kits for chromogranin A measurements. J Endocrinol. 2003;177(2):337-341.
12. ARUP's Laboratory Test Directory. Chromogranin A: 0080469. http://www.aruplab.com/guides/ug/tests/0080469.jsp. Accessed December 1, 2010.
13. InterScience Institute. Assays. http://www.interscienceinstitute.com/index.php?book/c. Accessed December 1, 2010.
14. LabCorp. Chromogranin A. https://www.labcorp.com/wps/portal/!ut/p/c1/hY1BDoIwEEXPwglmmNaxLIEQu7CEVCPt. Accessed December 1, 2010.
15. Mayo Clinic. Mayo Medical Laboratories – Unit Code 83559: Chromogranin A, Serum. http://www.mayomedicallaboratories.com/test-catalog/print.php?unit_code=83559. Accessed December 1, 2010.
16. Quest Diagnostics. Chromogranin A. http://www.questdiagnostics.com/hcp/qtim/testMenuSearch.do.#. Accessed December 1, 2010.
17. Modlin IM, Latich I, Zikusoka M, Kidd M, Eick G, Chan AKC. Gastrointestinal carcinoids: the evolution of diagnostic strategies. J Clin Gastroenterol. 2006;40(7):572-582.
12. ARUP's Laboratory Test Directory. Chromogranin A: 0080469. http://www.aruplab.com/guides/ug/tests/0080469.jsp. Accessed December 1, 2010.
13. InterScience Institute. Assays. http://www.interscienceinstitute.com/index.php?book/c. Accessed December 1, 2010.
14. ARUP's Laboratory Test Directory. Chromogranin A: 0080469. http://www.aruplab.com/guides/ug/tests/0080469.jsp. Accessed December 1, 2010.
15. InterScience Institute. Assays. http://www.interscienceinstitute.com/index.php?book/c. Accessed December 1, 2010.
16. LabCorp. Chromogranin A. https://www.labcorp.com/wps/portal/!ut/p/c1/hY1BDoIwEEXPwglmmNaxLIEQu7CEVCPt. Accessed December 1, 2010.