Table 3.
Clinical, histological, molecular and genetic features of patients with MMRd
| Case | Age/sex | CRC relation to splenic flexure | TNM | MSI status | Protein loss by IHC | BRAF V600E Mutation status | MLH1 Methylation | Gene tested | Result | Interpretation1 | Classification |
|---|---|---|---|---|---|---|---|---|---|---|---|
| D9 | 33 M | Proximal | II | MSI | MLH1/PMS2 | wt | 1% | MMRg + MUTYH | c.1852_1854del AAG of MLH1 | Deleterious | LS |
| 18 | 43 M | Proximal | II | MSI | PMS2 | PMS2 | c.861_864del ATTA of PMS2 | Deleterious | LS | ||
| A17 | 15 F | Proximal | III | MSS | PMS2 | PMS2 | c.24-?_2589 +?del of PMS2 | Deleterious | CMMR-D | ||
| B6 | 46 F | Proximal | II | MSI | MSH2/MSH6 | MSH2 | c.1840G>T of MSH2 | Deleterious | LS | ||
| 23 | 30 F | Distal | III | MSI | MSH2/MSH6 | MMRg + MUTYH | c.1760–30G of MSH2 | Suspected deleterious |
LS | ||
| A25 | 37 F | Proximal | II | MSI | MLH1/PMS2 | wt | 2% | MMRg + MUTYH | c.l942C>T of MLH1 | Deleterious | LS |
| A19 | 12 M | Distal | IV | MSI | MSH2/MSH6 | MMRg + MUTYH | Negative | LLS | |||
| C13 | 25 F | Proximal | III | MSI | MSH2/MSH6 | MMRg + MUTYH | Negative | LLS | |||
| D14 | 30 F | Proximal | II | MSI | MSH2/MSH6 | MMRg + MUTYH | Negative | LLS | |||
| A20 | 40 M | Distal | III | MSI | MLH1/PMS2 | wt | 2% | MMRg + MUTYH | Negative | LLS | |
| C4 | 31 F | Distal | III | MSI | MSH2/MSH6 | MSH2, MSH6, EPCAM + PM MUTYH | Negative | LLS | |||
| 24 | 34 M | Proximal | 1 | MSI | MSH2/MSH6 | MSH2, EPCAM + PM MUTYH | Negative | LLS | |||
| D30 | 36 M | Distal | III | MSI | PMS2 | wt | MLH1, PMS2 + PM MUTYH | Negative | LLS | ||
| D25 | 41 M | Proximal | II | MSI | MLH1 | wt | 1% | MLH1 + PM MUTYH | c.1852_1853delAAinsGC of MLH1 | Polymorphism 29,30 | LLS |
| C16 | 42 M | Proximal | II | MSI | MLH1/PMS2 | wt | 25% | Sporadic CRC | |||
| C12 | 43 M | Proximal | II | MSI | MLH1/PMS2 | wt | 26% | Sporadic CRC | |||
| D18 | 43 F | Distal | II | MSI | MLH1/PMS2 | wt | 27% | Sporadic CRC | |||
| D32 | 48 F | Distal | II | MSI | MLH1/PMS2 | wt | 51% | Sporadic CRC | |||
| A6 | 49 F | Proximal | III | MSI | MLH1/PMS2 | mutated | 88% | Sporadic CRC | |||
| D6 | 19 M | Proximal | IV | MSI | MSH2/MSH6 | Not tested | MMR deficient | ||||
| D29 | 28 F | Distal | III | MSI | Normal expression of 4 proteins | Not tested | MMR deficient |
M: male, F: female, MSI: microsatellite instability, MSS: microsatellite stability, IHC: immunohistochemistry of mismatch repair proteins, −: loss of protein expression in IHC, +: normal expression of proteins in IHC, wt: wild type, MLH1 Met: methylation levels (%) of MLH1’s promoter region, MMRg: all 5 mismatch repair genes (MLH1, MSH2, MSH6, PMS2 and EPCAM), MYH: full sequencing of MUTYH, PM MUTYH: prevalent MUTYH mutations (G393D and Y176C) LS: Lynch syndrome, LLS: Lynch-like syndrome.
1
Information about variant classification is detailed in Supporting Information Table S2.