Chromogranin A—Biological Function and Clinical Utility in Neuro Endocrine Tumor Disease

Modlin, Irvin M.; Gustafsson, Bjorn I.; Moss, Steven F.; Pavel, Marianne; Tsolakis, Apostolos V.; Kidd, Mark

doi:10.1245/s10434-010-1006-3

Cited by 387Neuroendocrine Tumor Research AdvancesPolyamine Metabolism and ApplicationsNeuropeptides and Animal Physiology

Chromogranin A—Biological Function and Clinical Utility in Neuro Endocrine Tumor Disease

Modlin, Irvin M., Gustafsson, Bjorn I., Moss, Steven F., Pavel, Marianne, Tsolakis, Apostolos V., Kidd, Mark·2010·Annals of Surgical Oncology

DOI 10.1245/s10434-010-1006-3

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Abstract

Background Neuroendocrine tumors (NETs) are a form of cancer that differ from other neoplasia in that they synthesize, store, and secrete peptides, e.g., chromogranin A (CgA) and amines. A critical issue is late diagnosis due to failure to identify symptoms or to establish the biochemical diagnosis. We review here the utility of CgA measurement in NETs and describe its biological role and the clinical value of its measurement. Methods Literature review and analysis of the utility of plasma/serum CgA measurements in NETs and other diseases. Results CgA is a member of the chromogranin family; its transcription and peptide processing are well characterized, but its precise function remains unknown. Levels are detectable in the circulation but vary substantially (approximately 25%) depending on which assay is used. Serum and plasma measurements are concordant. CgA is elevated in approximately 90% of gut NETs and correlates with tumor burden and recurrence. Highest values are noted in ileal NETs and gastrointestinal NETs associated with multiple endocrine neoplasia type 1. Both functioning and nonfunctioning pancreatic NETs have elevated values. CgA is more frequently elevated in well-differentiated tumors compared to poorly differentiated NETs. Effective treatment is often associated with decrease in CgA levels. Proton pump inhibitors falsely increase CgA, but levels normalize with therapy cessation. Conclusions CgA is currently the best available biomarker for the diagnosis of N…

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Proton pump inhibitor use is the most important reason for an elevated chromogranin A level not caused by neuroendocrine tumour disease.
“However, the use of proton pump inhibitors (PPIs) is the most important reason for an elevated CgA level, not caused by NET (Modlin et al, 2010).”
From Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumours (2011) · cites this paper as Modlin et al, 2010
Chromogranin A levels may also be elevated in other disease processes, such as prostate cancer, liver failure, cardiovascular diseases and renal failure.
“Chromogranin A levels may also be elevated in other disease processes, such as prostate cancer, liver failure, cardiovascular diseases and renal failure (Tramonti et al, 2001; Modlin et al, 2010; Vezzosi et al, 2011).”
From Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumours (2011) · cites this paper as Modlin et al, 2010
Patient 18 with liver metastases and renal failure had a chromogranin A decrease of 35% after proton pump inhibitor discontinuation.
“Patient 18 with liver metastases suffered also from renal failure (glomerular filtration rate=36 ml per minute per 1.73 m2), but even then the CgA level decreased with 35% (Modlin et al, 2010).”
From Discontinuation of proton pump inhibitors during assessment of chromogranin A levels in patients with neuroendocrine tumours (2011) · cites this paper as Modlin et al, 2010

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Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: More flaws than fame
Marotta, V., Zatelli, M. C., Sciammarella, C., Ambrosio, M. R., Bondanelli, M., Colao, A., & Faggiano, A. (2018) · Endocrine-Related Cancer · doi:10.1530/erc-17-0269 · Cited by 161 · see citing works
Chromogranin A—unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls
Gut, P., Czarnywojtek, A., Fischbach, J., Bączyk, M., Ziemnicka, K., Wrotkowska, E., Gryczyńska, M., & Ruchała, M. (2016) · Archives of Medical Science · doi:10.5114/aoms.2016.57577 · Cited by 144 · see citing works
Development of type I gastric carcinoid in patients with chronic atrophic gastritis: Type I gastric carcinoids in atrophic gastritis
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Effect of proton-pump inhibitor therapy on serum chromogranin A level.
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“However, the use of proton pump inhibitors (PPIs) is the most important reason for an elevated CgA level, not caused by NET (Modlin et al, 2010).”
BackgroundInfluential
Standard Pre- and Postoperative Determination of Chromogranin A in Resectable Non-Functioning Pancreatic Neuroendocrine Tumors—Diagnostic Accuracy: NF-pNET and Low Tumor Burden
Jilesen, A. P. J., Busch, O. R. C., van Gulik, T. M., Gouma, D. J., & Nieveen van Dijkum, E. J. M. (2014) · Digestive Surgery · doi:10.1159/000370007 · Cited by 26 · see citing works
Chromogranin As a Biochemical Marker of Neuroendocrine Tumors
Lyubimova, N. V., Churikova, T. K., & Kushlinskii, N. E. (2016) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-016-3254-0 · Cited by 20 · see citing works

Authors: Modlin, I. M., Gustafsson, B. I., Moss, S. F., Pavel, M., Tsolakis, A. V., & Kidd, M.
Affiliations: Yale University (US)
Brown University (US)
Charité – Universitätsmedizin Berlin (DE)
Uppsala University Hospital (SE)
Corresponding author: Modlin, Irvin M.
ORCID: Moss, Steven F.
Tsolakis, Apostolos V.
Kidd, Mark
Venue: Annals of Surgical Oncology
Publisher: Springer Science and Business Media LLC
Published: 2010-03-09
Volume: 17
Issue: 9
Pages: 2427-2443
ISSN: 1068-9265 (ISSN-L)
1534-4681
DOI: 10.1245/s10434-010-1006-3
OpenAlex: W2002962269
Cited by: 387
References: 151
Citations by year: 2026: 9 · 2025: 14 · 2024: 17 · 2023: 8 · 2022: 19 · 2021: 36 · 2020: 24 · 2019: 21 · 2018: 20 · 2017: 37 · 2016: 28 · 2015: 35 · 2014: 35 · 2013: 26 · 2012: 24
FWCI: 3.04
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Annals of Surgical Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Epidemiology › Neuroendocrine Tumor Research Advances
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: chromogranin A, neuroendocrine tumors, tumor markers, gastrointestinal neuroendocrine tumors, pancreatic neuroendocrine tumors, multiple endocrine neoplasia type 1, ileal neuroendocrine tumor, tumor recurrence, treatment response monitoring, proton pump inhibitors
MeSH terms: Humans, Prognosis, Biomarkers, Tumor, Neuroendocrine Tumors, Chromogranin A

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Chromogranin A—Biological Function and Clinical Utility in Neuro Endocrine Tumor Disease

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