Chromogranin A biomarker: What you need to know

Frequently Asked Questions

Q: How is CgA testing performed?
A: CgA can be measured in either plasma or serum.1 Several validated CgA assays that utilize serum or plasma samples are currently available commercially. Most CgA assays use either of 2 methodologies: radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA).2

Q: Is elevated CgA always indicative of a NET?
A: No. Certain other conditions can increase CgA levels, including proton pump inhibitor (PPI) therapy, chronic gastritis, inflammatory chronic diseases, renal or hepatic dysfunction, and arterial hypertension.3 For diagnostic accuracy, as well as continued disease management, preliminary biomarker results should be confirmed with diagnostic imaging and endoscopic techniques as well as histopathologic diagnosis when appropriate. Further biomarker tests might also help in diagnosis and management of NETs.

Q: Why is CgA a meaningful diagnostic tool for NETs?
A: CgA offers the best overall combination of sensitivity and specificity of any known circulating diagnostic marker for NETs.3,4 It can help detect NETs that produce very low levels of hormones, because CgA expression is independent of hormone secretion.5 Elevated CgA levels can raise the index of suspicion that a NET may be present. The diagnosis should then be confirmed using additional appropriate imaging and/or endoscopic techniques, as well as biopsy.

Q: What is the normal range for CgA?
A: There is no generally accepted normal range for CgA. Results may vary by laboratories, antibodies, reference standards, the ways in which results are expressed, and analytical sensitivity and specificity.2 In addition, ranges of CgA values can vary because NETs process and release different forms and amounts of CgA.2,6 Therefore, CgA results are comparable only when obtained using the same method.3 It is also important to keep in mind that other conditions can increase CgA levels without a NET being present, including patients receiving PPI therapy and those with chronic gastritis, renal and hepatic dysfunction, and arterial hypertension.3

Q: How can CgA be used in the ongoing management of patients with NETs?
A: CgA levels are correlated with tumor burden,7 health-related quality of life,8 and reduced survival times.7,8 Additionally, CgA increases precede radiologic evidence of disease progression and may provide the first evidence of recurrence in patients with resected NETs.4,9

Carcinoid Syndrome

Multidisciplinary Approach

Which NET patients does it affect and what can be done? Patients and HCPs alike can learn more about carcinoid syndrome at
www.carcinoid.com

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Expert Point of View

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1. O'Connor DT, Pandlan MR, Carlton E, Cervenka JH, Hsiao RJ. Rapid radioimmunoassay of circulating chromogranin A: in vitro stability, exploration of the neuroendocrine character of neoplasia, and assessment of the effects of organ failure. Clin Chem. 1989;35(8):1631-1637.
2. 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.
3. 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.
4. Eriksson B, Öberg K, Stridsberg M. Tumor markers in neuroendocrine tumors. Digestion. 2000;62(suppl 1):33-38.
5. Sobol RE, Memoli V, Deftos LJ. Hormone-negative, chromogranin A-positive endocrine tumors. N Engl J Med. 1989;320(7):444-447.
6. 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.
7. 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.
8. 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.
9. Welin S, Stridsberg M, Cunningham J, et al. Elevated plasma chromogranin A is the first indication of recurrence in radically operated midgut carcinoid tumors. Neuroendocrinology. 2009;89(3):302-307.