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 diagnostic markers.
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.