research
Neuroendocrine Tumour Markers
- Publication date
- 22 September 1999
- Publisher
- The 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.