The diversity of tumours with microsatellite instability: molecular mechanisms and impact upon microsatellite instability testing and mismatch repair protein immunohistochemistry.

Microsatellite instability (MSI) as a distinct molecular phenotype in human neoplasms was first recognised in 1993. Since then there has been tremendous progress in our understanding of this phenotype, including its genomic drivers and functional consequences. Currently, the multiple lines of investigation on MSI seem to have converged upon one important facet: its diversity, both genotypically and phenotypically, and both within and across tumour types. This review article offers a pathologist's perspective on our current understanding of this diversity, and highlights its potentially significant impact on the effective use of our current MSI detection tools: PCR- or sequencing-based MSI testing and mismatch repair protein immunohistochemistry.