Tumor Markers in Neuroendocrine Tumors

Abstract

Most neuroendocrine tumors produce and secrete a multitude of peptide hormones and amines. Some of these substances cause a specific clinical syndrome: carcinoid, Zollinger-Ellison, hyperglycemic, glucagonoma and WDHA syndrome. Specific markers for these syndromes are basal and/or stimulated levels of urinary 5-HIAA, serum or plasma gastrin, insulin, glucagon and vasoactive intestinal polypeptide, respectively. Some carcinoid tumors and about one third of endocrine pancreatic tumors do not present any clinical symptoms and are called ‘nonfunctioning’ tumors. Therefore, general tumor markers such as chromogranin A, pancreatic polypeptide, serum neuron-specific enolase and subunits of glycoprotein hormones have been used for screening purposes in patients without distinct clinical hormone-related symptoms. Among these general tumor markers chromogranin A, although its precise function is not yet established, has been shown to be a very sensitive and specific serum marker for various types of neuroendocrine tumors. This is because it may also be elevated in many cases of less well-differentiated tumors of neuroendocrine origin that do not secrete known hormones. At the moment, chromogranin A is considered the best general neuroendocrine serum or plasma marker available both for diagnosis and therapeutic evaluation and is increased in 50–100% of patients with various neuroendocrine tumors. Chromogranin A serum or plasma levels reflect tumor load, and it may be an independent marker of prognosis in patients with midgut carcinoids.

Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms) Part I—General Overview

“…Other general tumour markers are plasma pancreatic polypeptide (PP) and human chorionic gonadotrophin alfa-subunits (HCGá ). For each tumour type characteristic clinical symptoms should lead to measurement of specific markers such as gastrin, insulin, VIP, glucagons, and U-5-HIAA (14).…”

Circulating markers for endocrine tumours of the gastroenteropancreatic tract

“…In addition to the tumours that appear to secrete only pancreatic polypeptide (PP), the majority of all pancreatic endocrine tumours and about one-third of those arising in the GI tract also produce PP and secrete significant concentrations into the circulation. 31 Rare pancreatic endocrine tumours Other extremely rare pancreatic endocrine tumours include glucagon-like peptide 1 (GLP1)oma, glucagon-like peptide 2 (GLP2)oma, neurotensinoma, calcitoninoma, ACTHoma, cholecystokinin (CCK)oma and more. All of these may present as defined tumours or the above peptides may be co-secreted in addition to the existing tumour syndromes.…”

“…CGRP is elevated in MTC and in some lung carcinoid tumours (30%). 31,206 CGRP may be raised in some non-endocrine tumours, particularly in small cell lung tumours. 207 …”

Significance of plasma chromogranin A determination in neuroendocrine tumour (NET) diagnosis.

“…This physiological protein of MW 48 kDa [6][7][8] is produced and stored together with biogenic amines and other peptide hormones in the secretory granules called large dense-core vesicles of the neuroendocrine cells [2,[4][5][6]9,10], which are widespread in the whole organism and form the diffused endocrine system (DES) [11][12][13]. The neuroendocine cells can be found in: adrenal medulla, sympathetic nerves endings, cerebral cortex, pituitary gland, gastrointestinal tract, thyroid, parathyroid glands, pancreatic islets and lungs [2,4,8,10].…”

“…The neuroendocine cells can be found in: adrenal medulla, sympathetic nerves endings, cerebral cortex, pituitary gland, gastrointestinal tract, thyroid, parathyroid glands, pancreatic islets and lungs [2,4,8,10]. The synthesis and secretion of CgA may be intensified in the neuroendocrine tumour (NET) cells [4,9,14,15].…”