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  • Review Article
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Role of biomarker tests for diagnosis of neuroendocrine tumours

Nature Reviews Endocrinology volume 14, pages 656–669 (2018)Cite this article

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Abstract

Neuroendocrine tumours (NETs) are neoplasms that arise from neuroendocrine cells. Neuroendocrine cells and their tumours can secrete a wide range of amines and polypeptide hormones into the systemic circulation. This feature has triggered widespread investigation into circulating biomarkers for the diagnosis of NETs as well as for the prediction of the biological behaviour of tumour cells. Classic examples of circulating biomarkers for gastroenteropancreatic NETs include chromogranin A, neuron-specific enolase and pancreatic polypeptide as well as hormones that elicit clinical syndromes, such as serotonin and its metabolites, insulin, glucagon and gastrin. Biomarker metrics of general markers for diagnosing all gastroenteropancreatic NET subtypes are limited, but specific hormonal measurements can be of diagnostic value in select cases. In the past decade, methods for detecting circulating transcripts and tumour cells have been developed to improve the diagnosis of patients with NETs. Concurrently, modern scanning techniques and superior radiotracers for functional imaging have markedly expanded the options for clinicians dealing with NETs. Here, we review the latest research on biomarkers in the NET field to provide clinicians with a comprehensive overview of relevant diagnostic biomarkers that can be implemented in dedicated situations.

Key points

  • The diagnosis of gastroenteropancreatic neuroendocrine tumours (NETs) should be made by histological evaluation of tumour tissue, as the diagnostic accuracy of current circulating and imaging biomarkers is insufficient.

  • Clinicians should remain vigilant for the presence of hormonal syndromes in each patient with gastroenteropancreatic NETs, as these can attenuate prognosis, uncover specific biomarkers and facilitate tumour-specific management.

  • Chromogranin A, neuron-specific enolase and pancreatic polypeptide are circulating biomarkers with moderate to poor test characteristics for the diagnosis of gastroenteropancreatic NETs and should not be measured in patients as a means to screen for NET.

  • Circulating transcripts represent an emerging opportunity in the diagnosis of gastroenteropancreatic NETs, but whether they can be used to differentiate NETs from other tumours should be subject to further study, while their availability and cost-effectiveness in clinical practice remain to be determined.

  • PET of the somatostatin receptor and glucose metabolism is key to facilitating the delineation of tumour stage and individual treatment options and should be used in conjunction with anatomical imaging.

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Fig. 1: An overview of common biomarkers for gastroenteropancreatic NETs.
Fig. 2: An overview of targets for functional imaging in NETs.
Fig. 3: Somatostatin receptor imaging using two modalities.

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Review criteria

For our literature search, the National Center for Biotechnology Information PubMed online database was queried on 21 August 2017 with the following key words: “neuroendocrine” AND “biomarker”, yielding 6,779 papers. After screening of titles for biomarkers in gastroenteropancreatic neuroendocrine tumours, 421 original studies were left for abstract and, if available, full-text evaluation. Through cross-references, relevant studies that were not obtained through the original search were also included.

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  1. ENETS Center of Excellence, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands

    Johannes Hofland, Wouter T. Zandee & Wouter W. de Herder

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All authors researched data for the article, provided substantial contributions to discussions of the content, contributed equally to the writing of the article and reviewed and/or edited the manuscript before its submission.

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Hofland, J., Zandee, W.T. & de Herder, W.W. Role of biomarker tests for diagnosis of neuroendocrine tumours. Nat Rev Endocrinol 14, 656–669 (2018). https://doi.org/10.1038/s41574-018-0082-5

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