Table 2. Molecular Changes in Different Components of MiNENs of the Gastrointestinal Tract.
| MiNEN location | Molecular markers | Tumor composition |
Testing modality | Comment | Reference | |
|---|---|---|---|---|---|---|
| Adenocarcinoma | Neuroendocrine | |||||
| Gallbladder | 17p13 loh/tp53 | 92% | 77% | PCR (LOH) | There is a substantial overlap between the mutational profiles of gallbladder SCNEC and adenocarcinomas | [4] |
| 9p21 LOH INK4A | 50% | 44% | ||||
| 18q21 LOH/DPC4/DCC | 31% | 43% | ||||
| K-Ras | 0-17% | 17% | ||||
| Stomach | p53 | 73% (common mutational status in 11/15 cases) | Microdissection and direct sequencing | MiNEN components share the cell of origin | [32] | |
| Colon | Cyclin D1 | 100% | 19% | Immunohistochemistry | MiNENs evolve from a single epithelial precursor after an exocrine to neuroendocrine cell-type sequence | [33] |
| p53 | 53% | 74% | ||||
| β-catenin | 9% | 70% | ||||
| CDKN2A/B | 9.8%* | 6% | Genomic profiling | PDNEC mutational profiles are more specific for their primary locations, and similar to that of adenocarcinomas of the same site | [34] | |
| APC | 49.3%* | 47% | ||||
| Pancreas | CDKN2A/B | 28.3%* | 27% | [35] | ||
| APC | 2.5%* | 3% | ||||
*Mutational profiles are from: COSMIC database (http://cancer.sanger.ac.uk/cosmic). LOH: loss of heterozygosity; MiNEN: mixed neuroendocrine non-endocrine neoplasm; PCR: polymerase chain reaction; PDNEC: poorly differentiated neuroendocrine carcinoma; SCNEC: small cell neuroendocrine carcinoma.