[Frontiers in Bioscience S2, 332-342, January 1, 2010]

Biomarkers in neuroendocrine tumors

Massimiliano Berretta1, Alessandro Cappellani2, Maria Di Vita2, Salvatore Berretta2, Guglielmo Nasti3, Alessandra Bearz6, Umberto Tirelli 1, Vincenzo Canzonieri4

1Department of Medical Oncology, National Cancer Institute Aviano (Pn), 2 Department of Surgery, University of Catania, Catania, 3 Department of Colorectal Oncology/Medical Oncology, National Cancer Institute, G. Pascale Foundation Naples, 4Division of Pathology, National Cancer Institute Aviano


1. Abstract
2. Introduction
3. General tissue markers of neuroendocrine differentiation
3.1. Chromogranins
3.1.1. CgA
3.1.2. CgB
3.1.3. CgC
3.2. Synaptophysin
3.3. Neural cell adhesion molecule (NCAM CD56)
3.4. Vesicular monoamine Trasporter VMAT1 e VMAT2
3.5. Prohormone convertases (PC1, PC2)
3.6. Specific peptide hormone markers (gastrin, serotonin, somatostatin and others)
3.7. Somatostatin receptors
3.8. Pancreatic polypeptide
3.9. CD57
3.10. Ck19 Neuronal specific enolase (NSE)
3.11. PGP 9.5
3.12. Neurofilaments
3.13. Neuroendocrine secretory peptide 55 (pancreas)
3.14. Ghrelin (oxyntic mucosa)
3.15. CDx2 (ileum, appendix)
3.16. Thyroid transcription factor 1 (TTF-1)
3.17. Histidine decarboxylase (pancreas)
3.18. Xenin (duodenum)
3.19. Ki-67
4. Circulating markers for NETs
4.1. Chromogranin
4.2. Neuron-specific enolase
4.3. Human chorionic gonadotrophin
4.4. Alpha-fetoprotein
4.5. Pancreatic polypeptide
4.6. Calcitonin
4.7. Urinary 5-hydroxyindoleacetic acid
4.8. 5-hydroxy-tryptamine serotinine/5-hydroxy-tryptophane
4.9. Other circulating markers
5. Prognostic markers
6. Conclusions and Perspectives
7. Acknowledgments
8. References


Here we review the role of clinical biomarkers (tissue and circulating markers) in the management of neuroendocrine tumors. These tumors may originate in different organs, from cells embriologically different but expressing common phenotypic characteristics, such as the immuno-reactivity for markers of neuroendocrine differentiation (defined as "pan-neuroendocrine"), the capacity to secrete specific or aspecific peptide and hormones, and the expression of some receptors, that are at the basis of the current diagnostic and therapeutic approach.