Table 4.
MSI status and NGS analysis of MLH1, PMS2, MSH2 and MSH6 genes in FFPE tumour tissue and MLH1 methylation findings
| Case | MSI in MMR‐retained areas | MSI in MMR‐lost areas | NGS in MMR IHC‐retained regions | NGS in MMR IHC‐lost regions |
|---|---|---|---|---|
| Case 1 | MSS | MSI‐H (5/5) | No variants* | No variants*
MLH1 promoter hypermethylated (45%) |
| Case 2 | MSI‐H (5/5) | MSI‐H (5/5) |
MSH6 c.3261dupC (p.Phe1088Leufs*5) Allele Fraction: 19% PMS2 c.1289C>T (p.Thr430Ile) Allele Fraction: 24% PMS2 c.92 T>C (p.Val31Ala) Allele Fraction 28% |
MSH6 c.3260_3261dupCC (p.Phe1088Profs*3) Allele Fraction: 7% MSH6 c.3261dupC (p.Phe1088Leufs*5) Allele Fraction: 3% |
| Case 3 | MSS | MSS | No variants* | No variants* |
| Case 4 | MSI‐H (3/5) | MSI‐H (5/5) |
MSH6 c.3261delC (p.Phe1088Serfs*2) Allele Fraction:20% MSH6 c.3261dupC (p.Phe1088Leufs*5) Allele Fraction:10% |
MSH6 c.3261delC (p.Phe1088Serfs*2) Allele Fraction:34% MSH6 c.3261dupC (p.Phe1088Leufs*5) Allele Fraction:35% |
| Case 5: Pancreas cancer | MSI‐L (1/5) | Not applicable | No variants* | No variants* |
| Case 5: Gastric cancer | MSS | MSI‐H (5/5) | No variants* |
MSH6 c.3261delC (p.Phe1088Serfs*2) Allele Fraction: 22% |
| Case 5: Gastric dysplasia | MSS | MSI‐H (4/5) | No variants* |
MSH6 c.3261delC (p.Phe1088Serfs*2) Allele fraction: 17% MSH6 c.3261dupC (p.Phe1088Leufs*5) Allele Fraction: 13% MSH6 c.95G>A (p.Gly32Asp) Allele fraction:14% |
MSI‐H with number of markers showing instability out of a total of five possible markers indicated.
*
No Lynch syndrome‐associated germline variants were detected in the normal tissue from any of the five cases.