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

  • Endocrine Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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 (~25%) depending on which assay is used. Serum and plasma measurements are concordant. CgA is elevated in ~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 NETs. It is critical to establish diagnosis and has some utility in predicting disease recurrence, outcome, and efficacy of therapy. Measurement of plasma CgA is mandatory for the effective diagnosis and management of NET disease.

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Authors and Affiliations

  1. Gastrointestinal Pathobiology Research Group, Yale University School of Medicine, New Haven, CT, USA

    Irvin M. Modlin MD, PhD, DSc, FRCS, Bjorn I. Gustafsson MD, PhD & Mark Kidd PhD

  2. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

    Bjorn I. Gustafsson MD, PhD

  3. Department of Medicine, Rhode Island Hospital/Brown University, Providence, RI, USA

    Steven F. Moss MD

  4. Med. Klinik m.S. Hepatologie und Gastroenterologie, Charité—Campus Virchow Klinikum, Universitätsmedizin Berlin, Berlin, Germany

    Marianne Pavel MD

  5. Department of Medical Sciences, Section of Endocrine Oncology, University Hospital, Uppsala, Sweden

    Apostolos V. Tsolakis MD

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  1. Irvin M. Modlin MD, PhD, DSc, FRCS
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Correspondence to Irvin M. Modlin MD, PhD, DSc, FRCS.

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Modlin, I.M., Gustafsson, B.I., Moss, S.F. et al. Chromogranin A—Biological Function and Clinical Utility in Neuro Endocrine Tumor Disease. Ann Surg Oncol 17, 2427–2443 (2010). https://doi.org/10.1245/s10434-010-1006-3

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