Abstract
The diagnosis of neuroendocrine tumors (NETs) is a challenging task: Symptoms are rarely specific, and clinical manifestations are often evident only when metastases are already present. However, several bioactive substances secreted by NETs can be included for diagnostic, prognostic, and predictive purposes. Expression of these substances differs between different NETs according to the tumor hormone production. Gastroenteropancreatic (GEP) NETs originate from the diffuse neuroendocrine system of the gastrointestinal tract and pancreatic islets cells: These tumors may produce many non-specific and specific substances, such as chromogranin A, insulin, gastrin, glucagon, and serotonin, which shape the clinical manifestations of the NETs. To provide an up-to-date reference concerning the different biomarkers, as well as their main limitations, we reviewed and summarized existing literature.
Highlights
Neuroendocrine tumors (NETs) are a heterogeneous group of rare malignancies which, from a clinical point of view, represent a true challenge for clinicians at all stages of the disease
Different kits are available for measurement of circulating Chromogranin A (CgA): these assays might yield different results in relation to the forms of CgA and CgA-related peptide released from different neuroendocrine organs and NETs
Serum Neuron-Specific Enolase (NSE) concentrations are often increased in patients with other diseases, such as thyroid cancer, prostate carcinoma, neuroblastoma, and small cell lung carcinoma (SCLC) [8]; on the contrary, neuronal damage is associated with decreased levels of NSE [30]
Summary
Neuroendocrine tumors (NETs) are a heterogeneous group of rare malignancies which, from a clinical point of view, represent a true challenge for clinicians at all stages of the disease. Low-grade tumors are more often discovered much later in their clinical course due to rarely occurring symptoms, whereas the more dramatic onset of high-grade tumors is more closely associated with poor clinical prognosis Another classification is based on the patterns of peptides and amines secretion and defines NETs as either functioning or non-functioning [7]. Neuroendocrine markers might be divided in two “categories”, namely specific and non-specific markers, with the former being produced by functioning NETs and varying according to hormone production and the latter being produced by virtually all NETs [3,9,10] These markers are biologically active, and are, able to influence the clinical manifestations of the underlying NET: This is clearly demonstrated by the presence of different clinical syndromes, such as carcinoid syndrome or Zollinger-Ellison syndrome, which originate from the hypersecretion of the same substances which are “used” as markers of the disease. Biochemical confirmation of a NET should always be followed by imaging techniques aimed at assessing tumor size and relationship to adjacent structures
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