Research and practice in neuro-endocrine(NE) markers is focused on the detection and diagnosis of neuroendocrine
tumors (NETs), as epithelial neoplasms arise in many organs and are clinically characterised by an intriguingly
disperse behaviour, ranging from the almost invariably benign cases of carcinoids to the highly aggressive ones of small
In addition to specific hormonal peptides, NETs produce (and release) “general” NE markers, which constitute the distinctive
evidence of their differentiation.
The present review will focus on these “general” NE markers, belonging to six categories (see Table 1). The markers belonging
to the Granins family (chromogranins and secretogranins) are stored in the cytoplasmic secretory granules and
their most prominent component (Chromogranin A), a specific marker of NE differentiation, is currently detected by immunohistochemistry
on tumor sections and by ELISA procedures in the plasma. Membrane-related proteins (such as synaptophysin)
and cytoplasmic proteins (such as Neuron-specific Enolase and Protein-Gene product 9,5) are also important
Cell membrane-associated proteins (eg. Somatostatin receptors) and Transcription factors are also markers of interest in
NETs. In addition, special interest is presently dedicated to biomarkers such as phospho-mTOR and MGMT, potentially
predictive of responsiveness to selected drugs and of use in the selection of NET cases potentially responsive to tailored
therapy. In fact, the mammalian target of rapamycin (mTOR) represents a potential target for treatment, while differences
in MGMT expression might explain the sensitivity of some neuroendocrine tumors to temozolomide-based therapies.