Background/aims: A panel of five markers (two mononuclotide markers and three dinucleotide markers; the so-called Bethesda markers) has been proposed to define MSI status. However reducing these 5 markers into one or two markers have been suggested to be sufficient for detection of the MLH1- or MSH2-mutated Lynch syndrome. We attempted to examine the effectiveness of each Bethesda marker for the determination of MSI status clinically relevant to Lynch syndrome.
Methodology: We compared the MSI status obtained using each or a combination of two Bethesda markers to those obtained using all five Bethesda markers in 1,531 non-selected colorectal cancer patients.
Results: At least one mononucleotide marker was unstable in 94% of the MSI-H tumors defined by the Bethesda markers (126 of 134). After sequencing MLH1 and MSH2 genes from 31 of 86 patients eligible for the genetic test, 18 germline mutations were detected. Seventeen of these mutations were from high MSI tumors, and 1 was from a MSS tumor defined by 5 Bethesda markers. A combination of two mononucleotide markers was able to identify all 17 mutation-positive individuals with MSI-H tumors defined by the five Bethesda markers.
Conclusions: Instability in two mononucleotide markers, BAT26 and BAT25, was most effective markers at defining MSI status. Sensitivity is only slightly impaired by using two mononucleotide markers instead of five markers.