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.

Sample type and Volume required: 
Representative paraffin processed blocks of both tumour and normal tissue, ideally in separate blocks.
Turnaround time: 
2 – 3 weeks
Storage and transport: 
First class post within 4 days (temperature not to exceed 30°C during transport)
Cellular Pathology at Guy's And St Thomas' Hospital
Histology: 0207 188 8468, Cytology: 0207 188 2915, Oral Pathology: 0207 188 4367
Histopathology & Cytopathology Laboratories
Cellular Pathology
St Thomas' Hospital
North Wing - 2nd Floor
Westminster Bridge Road
London SE1 7EH

Head and Neck/Oral Pathology Laboratory
4th Floor, Tower Wing
Guy's Hospital
Great Maze Pond
London SE1 9RT

For clinical advice or interpretation of results, please contact the laboratory in the first instance.

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Last updated: 07/08/2015