Microsatellite Instability (MSI) and Mismatch Repair Protein Analysis

MSI is a key factor in several cancers particularly GI tract and gynaecological malignancies. Two mechanisms have been proposed for MSI occurrence. The first is in hereditary non-polyposis colorectal cancer (HNPCC) or Lynch Syndrome, where an inherited mutation in a mismatch-repair (MMR) gene causes a microsatellite repeat replication error to go unfixed. The second mechanism is the result of an epigenetic change which silences an essential MMR gene. In both cases, microsatellite insertions and deletions within polymorphic DNA regions result in uncontrolled cell division and tumor growth.


Expression of the MMR proteins involved, MSH2, MLH1, MSH6 and PMS2 can be detected by immunohistochemistry. No or low expression of one or more of these is indicative of MSI and should be further tested as below.


Five markers have been recommended by the National Cancer Institute to screen for MSI in HNPCC tumors (often called Bethesda markers). Generally, MSI detection in >30% of the markers is considered to be MSI-high (MSI-H) whereas microsatellite abnormalities in <30% of the markers is considered MSI-low.


Correlation between MMR protein expression and MSI is essential for patient management.