Abstract
Pancreatic neuroendocrine tumors (PanNENs) are rare sporadic cancers or develop as part of hereditary syndromes. PanNENs can be both functioning and non-functioning based on whether they produce bioactive peptides. Some PanNENs are well differentiated while others—poorly. Symptoms, thus, depend on both oncological and hormonal causes. PanNEN diagnosis and treatment benefit from and in some instances are guided by biomarker monitoring. However, plasmatic monoanalytes are only suggestive of PanNEN pathological status and their positivity is typically followed by deepen diagnostic analyses through imaging techniques. There is a strong need for new biomarkers and follow-up modalities aimed to improve the outcome of PanNEN patients. Liquid biopsy follow-up, i.e., sequential analysis on tumor biomarkers in body fluids offers a great potential, that need to be substantiated by additional studies focusing on the specific markers and the timing of the analyses. This review provides the most updated panorama on PanNEN biomarkers.
Highlights
Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors of epithelial origin arising from cells of the neuroendocrine system
In Pancreatic neuroendocrine tumors (PanNENs), alternative lengthening of telomeres (ALT) was shown to correlate with inactivating mutations in ATRX/DAXX genes [115, 116]
FDA defines as in vitro diagnostic (IVD) “any reagent, instrument, and/or system intended for use in diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or Liquid biomarkers include circulating cell-free DNA, circulating tumor cells (CTCs), small-non-coding molecules, as microRNAs or long non-coding RNAs, blood transcripts (e.g., NETest) and proteins (Table 4)
Summary
Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors of epithelial origin arising from cells of the neuroendocrine system. Evaluation of both NSE and CHGA concentration increases the reliability of NEN diagnosis; given the non-specific nature of these markers, they do not provide information on the primary tumor site and its origin [24]. PanNENs, Pancreatic Neuroendocrine Neoplasia; GEP-NENs, Gastro-Entero-Pancreatic Neoplasia; WD NETs, well differentiated tumors; Sens., sensibility; Spec., specificity.
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