Table 2.
Unexpected MMR Expression in MMR-Deficient Colorectal Cancers without MLH1 Methylation.
| Cases (n) | Cases with Retained MMR Expression n (%) | # | Age (yr) | Sex | Site | MSI | MMR Gene Mutation | Unexpected Expression of Afflicted MMR Gene by IHC* (% staining) | Expression of Corresponding Partner Gene by IHC (% staining) |
|---|---|---|---|---|---|---|---|---|---|
| Lynch Syndrome with Missense Mutations (9) | 4 (44%) | 1 | 48 | F | Rectum | MSS* | PMS2 c.137G>T, p.S46I; VUS (c.-7T>C) | PMS2 Intact* | MLH1 Intact |
| 2 | 44 | M | Descending | MSI-H* | PMS2 c.2113G>A, E705K | PMS2 WTC* (75%) | MLH1 Intact | ||
| 3 | 49 | M | Sigmoid | MSI-H | MSH6 c.1109T>C, p.L370S | MSH6 Intact | MSH2 Intact | ||
| 4 | 47 | M | Sigmoid | MSI-H | MSH6 c.1109T>C, p.L370S | MSH6 WTC (30%) | MSH2 Intact | ||
| Lynch Syndrome with Truncating Mutations (47) | 5 (11%) | 5 | 46 | F | Rectum | MSI-H | MLH1 c.2252_2253delAA, p.K751Sfs*3; MSH2 VUS (c.80C>T, p.P27L) | MLH1 Intact | PMS2 WTC (5%) |
| 6 | 29 | M | Rectum | MSS | PMS2 c.1281del, p.H428Tfs*20 | PMS2 Intact | MLH1 Intact | ||
| 7 | 51 | M | Rectum | MSI-H | MSH6 del promoter-exon 1 | MSH6 Intact | MSH2 Intact | ||
| 8 | 51 | M | Cecum | MSI-H | MSH6 c.3840_3846del, p.E1281Lfs*44 | MSH6 WTC (20%) | MSH2 Intact | ||
| 9 | 34 | M | Rectum | MSI-H | MSH6 c.3840_3846del, p.E1281Lfs*44 | MSH6 WTC (50%) | MSH2 WTC (80%) | ||
| Double Somatic MMR Mutations (26) | 7 (27%) | 10 | 59 | F | Ascending | MSI-H | MLH1 Hit 1: c.95T>A, p.I32N; Hit 2: LOH | MLH1 WTC (10%) | PMS2 Loss |
| 11 | 61 | M | Cecum | MSI-H | MLH1 Hit 1: c.2054C>A, p.S685Y; Hit 2: LOH | MLH1 WTC (10%) | PMS2 Loss | ||
| 12 | 61 | M | Ascending | MSI-H | MLH1 Hit 1: c.199G>A, p.G67R; Hit 2: LOH | MLH1 WTC (10%) | PMS2 WTC (30%) | ||
| 13 | 39 | M | Ascending | MSI-H | MLH1 Hit 1: c.2135G>A, p.W712X; Hit 2: c.2041G>A, p.A681T | MLH1 WTC (20%) | PMS2 Loss | ||
| 14 | 62 | M | Sigmoid | MSS | MLH1 Hit 1: c.298C>T, p.R100X; Hit 2: LOH | MLH1 WTC (75%) | PMS2 Loss | ||
| 15 | 60 | F | Transverse | MSI-H | MLH1 Hit 1: c.100G>A, p.E34K; Hit 2: LOH | MLH1 Intact | PMS2 Intact | ||
| 16 | 54 | M | Descending | MSI-H | MSH2 Hit 1: c.2038C>T, p.R680X; Hit 2: LOH | MSH2 WTC (>95%) | MSH6 WTC (80%) | ||
*
IHC = Immunohistochemistry; Intact = Diffuse Strong Staining Equal to or Greater than Control; LOH=loss of heterozygosity; MMR=Mismatch Repair Protein; MSI-H= Microsatellite Instable-High; MSS=Microsatellite Stable; WTC=Weaker Than Control.