Table 3.
Immunohistochemical (IHC) biomarkers for PanNENs diagnosis, prognosis and treatment monitoring.
| Immunohistochemical markers (IHC) | Source | Level | Combinations improving sens./spec. | Clinical use | References | ||
|---|---|---|---|---|---|---|---|
| Differentiation | Chromogranin A | CHGA | Surgical/endoscopic biopsy | Over-expressed | SYP | Diagnosis of NENs; Grading; Differentiation | (23) (24) |
| Synaptophysin | SYP | Surgical/endoscopic biopsy | Over-expressed | CHGA | Diagnosis of GEP-NENs; grading; differentiation | (24) | |
| Site of Origin | Insulin gene neanche homeeobox - 1 | ISL-2 | Surgical/endoscopic biopsy | Over-expressed in endocrine pancreas | Low expression in case of Gastrinoma | Over-expressed in Pan NENs (especially in WD tumors) | (55) |
| Progesteron Receptor | PGR | Surgical/endoscopic biopsy | Positive | CHGA + SYP | Indicative of pancreatic origin (40-75%) (negative in GI-NENs) | (56) | |
| Pancreatic and duodenal homeobox 1 | PDX-1 | Surgical/endoscopic biopsy | Positive | CHGA + SYP | Indicative of pancreatic origin | (57) | |
| Neuroendocrine secretory protein 55 | NESP55 | Surgical/endoscopic biopsy | Focally positive | CHGA + SYP | Indicative of pancreatic origin (40−50%) | (56) | |
| Prognostic/ Predictive | Somatostatin receptors 2a | SSTR2a | Surgical/endoscopic biopsy | Over-expressed | CHGA + SYP | Indicative of pancreatic origin; Predictive for PRRT treatment; inverse correlation with grading. | (58) (59) |
| ATRX/DAXX | ATRX/ DAXX | Surgical/endoscopic biopsy | Loss of expression | CHGA + SYP | Prognostic for tumor aggressiveness; (associated with WD tumors) | (60) | |
| Programmed Cell Death Ligand | PD-L1 | Surgical/endoscopic biopsy | Over-expressed | CHGA + SYP | Prognostic/Predictive for anti-PD-L1 therapeutic agents | (61) | |
PanNENs, Pancreatic Neuroendocrine Neoplasia; GEP-NENs, Gastro-Entero-Pancreatic Neoplasia; WD NETs, well differentiated tumors.