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/ Histopathology at King's College Hospital
020 3299 3045 - General Queries
King's College Hospital
Bessemer Wing - 2nd Floor
Denmark Hill
London SE5 9RS
For clinical advice or interpretation of results, please contact the laboratory in the first instance.

Boland, C. et al. (1998). A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for determination of microsattelite instability in colorectal cancer. Cancer Res 58: 5248-57.

Aaltonen, L. A et al. (1998). Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease. New England Journal of Medicine 338: 1481-1487.

Loukola, A, et al. (1999). Strategies for screening for hereditary non-polyposis colorectal cancer. J Med Genet 36: 819-822.

Gryfe, R et al. (2000) Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. NEJM 342: 69-77

Blanes A and Diaz-Cano S. (2006) Complementary analysis of microsatellite tumour profile and mismatch repair defercts in colorectal carcinomas.WJO 12:5932-40.

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Last updated: 07/08/2015