Table 3.
The main markers related to metastasizing PPGLs.
| Potential Marker | Characteristics Associated with Malignancy |
|---|---|
| Histopathological markers | |
| Grading system for adrenal pheochromocytoma and paraganglioma (GAPP) | Well-differentiated and moderately differentiated tumors |
| Tumor size and weight | On average, larger than 10 cm and more than 500 g |
| Adrenal gland scaled score (PASS) | ≥4 |
| Ki-67 proliferation index | >2% |
| Sustentacular cells | Cell density depletion or absent |
| Galectin-3 (LGALS3) | Increased expression detected using IHC staining |
| Succinate dehydrogenase complex subunit B (SDHB) | Negative or weak diffuse IHC staining |
| Heparanase-1 (HPSE1) | Positive IHC staining |
| Cyclooxygenase-2 (COX2) | |
| Genetic markers | |
| Succinate dehydrogenase complex subunit B (SDHB) | Germline mutation |
| Succinate dehydrogenase complex subunit D (SDHD) | |
| Fumarate hydratase (FH) | |
| Solute carrier family 25 member 11 (SLC25A11) | |
| Malate dehydrogenase 2 (MDH2) | |
| ATRX chromatin remodeler (ATRX) | Somatic mutation |
| Histone-lysine N-methyltransferase SETD2 (SETD2) | |
| Telomerase reverse transcriptase (hTERT) | |
| Mastermind-like transcriptional coactivator 3 (MAML3) | Fusion gene |
| CpG island methylator phenotype (CIMP) | High CIMP |
| MicroRNA miR-15a | Downregulation |
| Phenylethanolamine N-methyltransferase (PNMT) | |
| MicroRNA miR-483-5p | Overexpression |
| MicroRNA miR-101 | |
| MicroRNA miR-210 | |
| MicroRNA miR-21-3p | |
| MicroRNA miR-183-5p | |
| Telomerase reverse transcriptase (hTERT) | |
| Biochemical markers | |
| Normetanephrine and 3-methoxytyramine | Increased plasma or urine level |
| Neuron-specific enolase (NSE) | Increased serum level |