Biochemical diagnosis of neuroendocrine GEP tumor

Yale J Biol Med. Sep-Dec 1997;70(5-6):501-8.


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.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism*
  • Carcinoid Tumor / diagnosis
  • Carcinoid Tumor / metabolism
  • Chromogranin A
  • Chromogranins / analysis
  • Chromogranins / metabolism
  • Gastrins / blood
  • Humans
  • Hydroxyindoleacetic Acid / urine
  • Hypoglycemia / diagnosis
  • Hypoglycemia / metabolism
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / metabolism*
  • Neuropeptides / blood
  • Secretin / blood
  • Stimulation, Chemical
  • Tachykinins*
  • Zollinger-Ellison Syndrome / diagnosis
  • Zollinger-Ellison Syndrome / metabolism


  • Biomarkers, Tumor
  • Chromogranin A
  • Chromogranins
  • Gastrins
  • Neuropeptides
  • Tachykinins
  • neuropeptide K
  • Secretin
  • Hydroxyindoleacetic Acid