Table 1.
Clinical and Pathologic Features of Patients with and without Lynch Syndrome
| Clinical and Pathologic Features | Confirmed Lynch Syndrome N (%) | Non-Lynch Syndrome |
p-value*** | |||
|---|---|---|---|---|---|---|
| Overall N (%) | Lynch-like Syndrome** N (%) | Sporadic MLH1 Protein Deficiency N (%) | MMR Proficient N (%) | |||
| No. of cases | 52 | 70 | 10 | 30 | 30 | NA |
| Tumor location | ||||||
| Right colon | 32 (62) | 49 (70) | 6 (60) | 26 (87) | 17 (57) | 0.3 |
| Left colon / rectum | 20 (40) | 21 (30) | 4 (40) | 4 (13) | 13 (43) | |
| Mean age in years (range) | 52 (27–80) | 70 (37–93) | 60 (37–76) | 76 (57–93) | 68 (46–92) | <0.001 |
| Gender, Male/Female | 25 (48) / 27 (52) | 31 (56) / 39 (44) | 7 (70) / 3 (30) | 9 (30) / 21 (70) | 15 (50) / 15 (50) | 0.7 |
| Germline mutation analysis | ||||||
| MLH1 pathogenic variant present | 13 (25) | NA | 0 (0) | NA | NA | NA |
| MSH2 pathogenic variant present | 25 (48) | 0 (0) | ||||
| MSH6 pathogenic variant present | 8 (15) | 0 (0) | ||||
| PMS2 pathogenic variant present | 6 (12) | 0 (0) | ||||
| MMR protein expression in tumor | ||||||
| Intact expression of all 4 proteins | 1 (2) | 30 (43) | 0 (0) | 0 (0) | 30 (100) | <0.001 |
| MLH1 and PMS2 Loss | 13 (25) | 35 (50) | 5 (50) | 30 (100) | 0 (0) | |
| MSH2 and MSH6 Loss | 24 (46) | 2 (3) | 2 (20) | 0 (0) | 0 (0) | |
| Isolated MSH6 Loss | 8 (15) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| Isolated PMS2 Loss | 6 (12) | 3 (4) | 3 (30) | 0 (0) | 0 (0) | |
| MMR protein expression of affected | ||||||
| MMR gene in normal intestinal crypts* | ||||||
| Intact expression | 34 (65) | 69 (99) | 9 (90) | 30 (100) | 30 (100) | <0.001 |
| Loss of expression | 18 (35) | 1 (1) | 1 (10) | 0 (0) | 0 (0) | |
| MLH1 | 4 | 0 | 0 | |||
| MSH2 | 7 | 1 | 1 | |||
| MSH6 | 4 | 0 | 0 | |||
| PMS2 | 3 | 0 | 0 | |||
| Mean length of non-neoplastic mucosa evaluated by IHC in millimeters (range) | 105 (5–336) | 112 (10–399) | 187 (88–290) | 138 (41–399) | 61 (10–179) | 0.6 |
| Mean estimated number of non-neoplastic intestinal crypts evaluated by IHC (range) | 1163 (56–3733) | 1330 (111–5424) | 2195 (1089–3533) | 1659 (567–5424) | 712 (111–2268) | 0.3 |
MMR, mismatch repair; IHC, immunohistochemistry; Loss, loss of expression
*
Affected MMR gene is that which has germline MMR gene pathogenic variant or obligate partner of the MMR protein pair with a tumor showing concurrent loss of MMR protein expression.
**
Defined as loss of expression of one or more MMR proteins but with no explanation found (no germline variants or MLH1 promoter hypermethylation).
***
p-value is patients with Lynch syndrome versus patients without Lynch syndrome