Neuroendocrine Tumour Markers

textabstractThe neuroendocrine cells of the gastroenteropancreatic (GEP) axis belong to the APUD-system, because they are capable of amine precursor uptake and decarboxylation, leading to the production of amines and small peptides. Currently, over 50 peptides have been identified, secreted by more than IS different types of neuroendocrine cells scattered throughout the gut. Tumours of these cells are generally characterized by an excessive production of one or several of these peptides. The presence of peptides in tumour tissue can usually be easily identified with immunohistochemical methods, or by demonstrating their mRNA with in situ hybridization techniques . The peptides are also frequently released into the circulation, where they can exert their endocrine effects on various targets, often inducing a typical clinical syndrome of hormonal overproduction. These tumours can be called clinically jilllctioning neuroendocrine tumours. The circulating peptides can usually be measured with radioimmunologic methods, allowing them to be used as tumour markers. One tumour generally releases several amilles or peptides in the circulation. Therefore the choice of possible tumour markers is much wider than in the case of non-endocrine tumours. The situation is much more difficult in so-called clinically nonjilllctioning neuroendocrine tumours, not inducing symptoms or signs relating to hormonal hypersecretion. Sometimes, these tumours remain hormonally active, producing peptides without clinical effect, which still can be used as tumour markers. When the tumour has lost all abilities to produce hormonally active substances one has to resort to the use of non-endocrine secretion markers, such as certain enzymes or other contents of secretory granules. In the choice of an adequate tumour marker, the following criteria should be taken into account: the marker must be useful (l) to screen populations for the presence of a tumour, (2) to differentiate between the different types of neuroendocrine tumours, (3) to distinguish between benign, intermediate or malignant tumour types, (4) to provide an estimate of the tumour load, (5) to follow the course of a particular tumour over time, in order to be able to evaluate the response to therapeutic interventions, and to rapidly detect an eventual relapse, and (6) to assess the prognosis. Unfortunately none of the current tumour markers can fulfill all these goals. Therefore, the search for better markers still goes on, and is at present one of the main activities of neuroendocrine research. In addition to the use of the circulating peptides themselves, the receptors for some peptides have recently been shown to be velY valuable markers. Their presence on tumour tissue can be demonstrated in vivo by radioisotopic techniques, using radionuclide labeled peptide, which specifically binds to a specific receptor