ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Biochemical Markers

Kjell Oberg, Anne Couvelard, Gianfranco Delle Fave, David Gross, Ashley Grossman, Robert T. Jensen, Ulrich Frank Pape, Aurel Perren, Guido Rindi, Philippe Ruszniewski, Jean Yves Scoazec, Staffan Welin, Bertram Wiedenmann, Diego Ferone

Research output: Contribution to journalArticlepeer-review


Biomarkers have been the mainstay in the diagnosis and follow-up of patients with neuroendocrine tumors (NETs) over the last few decades. In the beginning, secretory products from a variety of subtypes of NETs were regarded as biomarkers to follow during diagnosis and treatment: Serotonin for small intestinal (SI) NETs, and gastrin and insulin for pancreatic NETs. However, it became evident that a large number of NETs were so-called nonfunctioning tumors without secreting substances that caused hormone-related symptoms. Therefore, it was necessary to develop so-called "general tumor markers." The most important ones so far have been chromogranin A and neuron-specific enolase (NSE). Chromogranin A is the most important general biomarker for most NETs with a sensitivity and specificity somewhere between 60 and 90%. NSE has been a relevant biomarker for patients with high-grade tumors, particularly lung and gastrointestinal tract tumors. Serotonin and the breakdown product urinary 5-hydroxyindoleacetic acid (U-5-HIAA) is still an important marker for diagnosing and follow-up of SI NETs. Recently, 5-HIAA in plasma has been analyzed by high-performance liquid chromatography and fluorometric detection and has shown good agreement with U-5-HIAA analysis. In the future, we will see new tests including circulating tumor cells, circulating DNA and mRNA. Recently, a NET test has been developed analyzing gene transcripts in circulating blood. Preliminary data indicate high sensitivity and specificity for NETs. However, its precise role has to be validated in prospective randomized controlled trials which are ongoing right now.

Original languageEnglish
Pages (from-to)201-211
Number of pages11
Issue number3
Publication statusPublished - Sep 1 2017


  • Biomarkers
  • Chromogranin A
  • Neuroendocrine tumor test
  • Urinary 5-hydroxyindoleacetic acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience


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