Specific and Non-Specific Biomarkers in Neuroendocrine Gastroenteropancreatic Tumors

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.

Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study)

“…Nonetheless, as 2‐ to 3‐times higher serum gastrin levels were sustained in subjects treated with vonoprazan compared with those treated with lansoprazole, attention should still be paid to possible occurrence of severe hypergastrinemia that may induce NETs during vonoprazan treatment, particularly long‐term treatment. Several circulating proteins have been accepted as diagnostic markers for NETs and may be used to monitor the risk of these malignancies during long‐term acid suppression by vonoprazan.…”

“…15 In recent studies, vonoprazan administered at 10 or 20 mg OD for up to 1 year or even longer increased serum gastrin level but was tolerated well in patients with healed GERD or peptic ulcer. [44][45][46] Nonetheless, as 2-to 3-times higher serum gastrin levels were sustained in subjects treated with vonoprazan 47,48 and may be used to monitor the risk of these malignancies during long-term acid suppression by vonoprazan.…”

Biomarkers for Pancreatic Neuroendocrine Neoplasms (PanNENs) Management—An Updated Review

“…NSE has low sensibility but relatively high specificity (see Table 2). Indeed, NSE can be virtually overexpressed also by several non-neuroendocrine tumors, such as parathyroid cancer, prostate carcinoma, neuroblastoma, and it has been correlated with poor differentiation, prognosis and high-grade disease (24). For these reasons NSE alone is rarely used for diagnostic purposes or to distinguish NENs from nonendocrine tumors.…”

Update on Histological Reporting Changes in Neuroendocrine Neoplasms

“…In the setting of functional NEN, detection of hormones may be of importance [ 24 , 25 ]. Especially in the setting of multiple neuroendocrine tumours, such as in the Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome, expression analysis of glucagon, insulin, gastrin and pancreatic polypeptide allows identification of which one is the tumour responsible for a hormonal syndrome.…”