Table 10.
Molecular profiling studies on miscellaneous pNET-associated proteins and pathways.
| Technique | Reference | Key Findings |
|---|---|---|
| IHC | [107] | In total, 17 out of 21 patients (81%) pNETs showed strong immunoreactivity for Myc. |
| IHC | [260] | Positive Myc expression in all 39 benign or metastatic pNETs. |
| Microarray | [270] | Upregulation of LCK, a Src family kinase, in primary (n = 8) and metastatic pNETs (n = 5), and pNET cell lines compared to normal islets. Microarray results were validated by qRT-PCR and IHC. |
| qPCR and IHC | [130] | RABL6A amplification in 6 of 11 primary pNETs and their matched metastases. High RABL6A protein expression observed by IHC in all pNETs (n = 5). |
| IHC | [271] | Significant upregulation of all HDACs (I, IIa, IIIb, III and IV) in pNETs whose expression was found correlate with tumor grading and predict disease outcomes. |
| RNA seq | [261] | Transcriptome analysis of 212 patient GEP-NETs complemented by systematic drug perturbation assays identified HDAC class I inhibitor, entinostat, as a potent agent to treat 42% GEP-NET patients. |
| RNA Seq | [106] | IPA and cMAP analysis of differentially expressed genes in 43 primary pNETs vs. their matched metastases predicted HDAC as one of the top pharmacological targets to treat metastatic pNETs. |
| IHC | [185] | Positive immunoreactivity for HSP90 and TGF-βRI in 75% of 67 primary and metastatic pNETs. |
| IHC | [262] | Positive aurora kinase A expression in 8 of 10 insulinomas, in all of 13 nonfunctional pNETs and 20 SBNETs. |
| IHC | [272] | Ptch1, the sonic hedgehog receptor, expressed in 12 of 22 sporadic pNETs and 4 of 5 MEN-1 pNETs with no significant correlation with clinical outcomes. |
| IHC | [273] | Nuclear β-catenin immunostaining in higher percentage of stage III/IV pNETs (2/13, 15%) vs. stage I/II pNETs (0/74). Negative APC expression in 70% (57/81) of the cases. |
| IHC | [274] | Positive expression of TGF-β, TGF-βRI, and TGF-βRII in 75–100% patient pNETs. |
| LOH and sequencing | [275] | LOH of Smad3 in 20% of 20 pNETs; no inactivating Smad3 mutations observed. |
| PCR and SSCP mutational analysis | [276] | DPC4 mutation or deletion detected in 55% (5 of 9) non-functional pNETs in contrast to none of the 16 functional tumors-insulinomas, gastrinomas, and VIPnomas. |