Microsatellite instability (MSI) testing by PCR method
Microsatellite Instability (MSI) test is a molecular genetic analysis that helps detect defects in the DNA mismatch repair (MMR) system.
Disruptions in this system lead to the accumulation of errors in repetitive DNA sequences known as microsatellites, which may be associated with an increased risk of certain cancers, including colorectal and endometrial cancer.
The MMR system is responsible for identifying and correcting errors that occur during DNA replication (such as the insertion of incorrect nucleotides).
The MMR system includes several proteins, such as:
- MLH1
- MSH2
- MSH6
- PMS2
Alterations in these genes (such as mutations or epigenetic changes) result in a failure to correct microsatellite errors, causing their instability — MSI.
MSI plays a crucial role in cancer development and can be used for diagnosis and prognosis. This is particularly important for the following types of cancer:
Colorectal Cancer (Colon Cancer)
- MSI is commonly found in patients with Lynch syndrome. This hereditary condition leads to DNA repair defects and an increased risk of colorectal cancer as well as other types of cancer. MSI tumors may have a better prognosis and higher sensitivity to immunotherapy.
Endometrial Cancer (Uterine Cancer)
- MSI is also frequently observed in endometrial tumors in women with Lynch syndrome.
Other Types of Cancer
- Stomach, ovarian, bladder, and other cancers may be associated with MSI, particularly if the patient has Lynch syndrome.
Prognosis: Tumors with MSI often have a more favorable prognosis because they may be less aggressive.
Immunotherapy: MSI tumors (especially in the context of Lynch syndrome) may be more sensitive to treatment with immunotherapeutic drugs. For example, checkpoint inhibitors (e.g., pembrolizumab) may be effective in treating these tumors.
Material: Paraffin blocks containing tumor tissue.
Procedure: Polymerase chain reaction (PCR) is performed followed by analysis of microsatellite marker length.
Quality Requirements: For accurate results, tumor tissue must constitute at least 20–30% of the total sample volume