Neuroendocrine gut and pancreatic
tumors are known to contain and secret different
peptide hormones and
amines. During the last two decades, many radioimmunoassays and Elizas have been developed to analyze these substances in blood and urine, which has enabled clinicians to improve the diagnosis and monitoring of patients with various
neuroendocrine tumors. Due to cost constraints in medical care, it is important to try to define the most useful
biochemical markers from the clinical point of view. The
glycoprotein chromogranin A has been shown to be a useful marker for diagnosing various
neuroendocrine tumors, both by histopathology and circulating
tumor markers. In patients with demonstrable endocrine
tumors, about 90 percent of the patients present high circulating levels of
chromogranin A. A hundred-fold increase of plasma
chromogranin is seen in patients with midgut
carcinoid tumors and liver
metastases. The plasma levels of
chromogranin A reflect the
tumor mass and can be used for monitoring the patient during treatment and follow-up, although the day-to-day variation might be 30-40 percent. High circulating levels of the
chromogranin A might be an
indicator of bad prognosis in patients with malignant
carcinoid tumors. Besides analyzing plasma
chromogranin A, specific analyses such as urinary
5-HIAA in midgut
carcinoid patients, serum
gastrin in patients with
Zollinger-Ellison syndrome and
insulin/
proinsulin in patients with
hypoglycemia should be performed. In patients with small
tumor masses or intermittent symptoms, provocative tests such as a meal stimulation test,
secretin test or
pentagastrin stimulation of
tachykinin release can supplement the basal measurements of
peptides and
amines. To fully evaluate the growth potential in
neuroendocrine tumors, traditional
biochemical markers should be supplemented with indicators of growth proliferation (Ki-67, PCNA) and immunohistochemical staining for the adhesion molecule CD44 and the
PDGF-alpha receptor. Finally, analysis of
somatostatin receptor subtypes and induction of the
enzymes 2-5A syntethase and PKR are of clinical value.