Table 2.
Biochemical biomarkers in use for PanNEN diagnosis, prognosis, and treatment monitoring.
| Biochemical markers | Source | Level | Sens. (%) | Spec. (%) | Combinations improving sens./spec. | Clinical use | References | ||
|---|---|---|---|---|---|---|---|---|---|
| Non–specific | Chromogranin A | CHGA | Serum | 63–14.750 ug/l | 60–83 | 72–85 | NSE; PP | For diagnosis and follow up in GEP-NENs and treatment monitoring | (20, 21) (22, 23) |
| Neuron-specific enolase | NSE | Plasma | 5–92 ug/l | 33 | 73 | CHGA | For diagnosis and follow up in GEP-NENs and treatment monitoring | (20, 21) (22, 23) | |
| Pancreatic-Polipetide | PP | Plasma | 480–780 pg/ml | 31-63 | 67 | CHGA | For diagnosis and follow up in PanNENs | (23) | |
| Human Corionic Gonadotropin | HCG | Serum | Increased | na | Na | AFP; CHGA; PP; HCG | Indicative of pancreatic origin | (24) | |
| Alpha Fetoprotein | AFP | Serum | Increased | na | Na | HCG; CHGA; PP | Indicative of pancreatic origin and de-differentiation | (25, 26) | |
| Specific | Gastrin | GAS | Serum | ≥300 pg/mL | 94 | 100 | MEN-1; ZES | Diagnostic for Gastrinoma of pancreatic origin | (24, 27) |
| Insulin | INS | Serum/ Plasma | ≥43∙ pmol/L | 52 - 94 | 92−100 | Whipple's triad | Diagnostic for Insulinoma; suggesting for WD NETs. | (28) | |
| Glucagon | GCG | Plasma | 500–1000 pg/mL | High | High | - | Diagnostic for Glucagonoma; suggesting for WD NETs; Indication for liver metastases | (24) | |
| Somatostatin | SST | Plasma | Increased° | na | Low | SSoma syndrome° | Diagnostic for SSoma of pancreatic origin; | (24) | |
| Vasoactive Intestinal Peptide | VIP | Serum/Plasma | 75∙−200 pg/dL | na | na | Verner Morrison | Diagnostic for ViPoma of pancreatic tail origin. | (29) | |
PanNENs, Pancreatic Neuroendocrine Neoplasia; GEP-NENs, Gastro-Entero-Pancreatic Neoplasia; WD NETs, well differentiated tumors; Sens., sensibility; Spec., specificity. ∙Diagnostic serum/plasma level in association with specific syndrome. °Somatostatin increase is very a-specific, increase SS level with SSoma syndrome is suggesting for GEP-NENs.