Does MSI-low exist?

Microsatellite instability is a well-recognised phenomenon. Ten to 15% of sporadic colorectal cancers with a high level of MSI form a well defined group with distinct clinicopathological features. The set of tumours with low level of microsatellite instability (MSI-low), though widely referred to, is not a clearly defined group. The definitions of MSI-low have varied among groups and between different studies from the same group. Some studies have found associations between the MSI-L phenotype and molecular features, notably a higher frequency of K-ras mutations, and, possibly, methylation of methylguanine methyltransferase. Two recent independent studies, however, showed respectively that 68% and 79%, non-MSI-H cancers showed some MSI and could therefore be classed nominally as MSI-L. There was no evidence for a qualitatively discrete MSI-L group, but quantitative differences in the level of MSI were found.