Table 1

Outcomes of non-methylated mismatch repair-deficient colorectal cancer

IHC resultnLynch syndromeDouble somaticUnexplainedFalse-positive IHC
Total combined283 157 92 19 17
55.6% of dMMR 32.5% of dMMR 6.7% of dMMR 6% of dMMR
Ohio
 Absent MLH1/PMS27528* (37.3%) 45 (60%) 1† (1.3%)1 (1.3%)
 Absent MSH2/MSH680 55 (68.8%) 18 (22.5%)6† (7.5%)1 (1.3%)
 Absent MSH633 19 (57.6%) 5‡ (15.2%)3*† (9.1%)6§ (18.2%)
 Absent PMS229 21 (72.4%) 5 (17.2%)1 (3.5%)2 (6.9%)
 IHC intact (MSI-H)17 11(64.7%) 3 (17.6%)3 (17.6%)0
Total Ohio232 134 76 14 10
57.8% of dMMR 32.8% of dMMR 6% of dMMR 4.3% of dMMR
Iceland
 Absent MLH1/PMS2101 (10%) 8 (80%) 1† (10%)0
 Absent MSH2/MSH6112 (18.2%) 5 (45.5%) 4 (36.4%)0
 Absent MSH612 7 (58.3%) 1 (8.3%)04 (33.3%)
 Absent PMS216 11 (68.8%) 2 (12.5%)03 (18.8%)
 IHC intact (MSI-H)2 2 (100%)NANANA
Total Iceland51 23 16 5 7
45.1% of dMMR 31.4% of dMMR 9.8% of dMMR 13.7% of dMMR
  • *One patient had both a germline MMR pathogenic variant (MLH1) and unexplained absence of MSH6 on IHC and is counted twice in the table percentages (Lynch syndrome MLH1/PMS2 and unexplained MSH6) but once in the Total Ohio denominator (Lynch).

  • †Four Ohio unexplained patients and one Iceland unexplained patient had insufficient material for tumour sequencing.

  • ‡One patient had both a germline MMR pathogenic variant (PMS2) and double somatic pathogenic variants (MSH6) and is counted twice in the table percentages (Lynch syndrome normal IHC and double somatic MSH6) but once in the Total Ohio denominator.

  • §One rectal cancer after radiation therapy (RT), biopsy was MMR proficient.

  • ¶These two patients had weak MSH6 stains and had a pathogenic second hit to MSH6 on tumour testing.

  • dMMR, mismatch repair deficient; IHC, immunohistochemistry; MSI-H, microsatellite instability-high; NA, not assessed.