Microsatellite Instability Testing by Immunohistochemistry

Function

Microsatellite Instability (MSI) testing by Immunohistochemistry (IHC) is a specialized pathological assessment used to detect deficiencies in DNA mismatch repair (MMR) proteins. The test evaluates the presence of four specific proteins: MLH1, MSH2, MSH6, and PMS2. When these proteins are absent, the cell's ability to fix DNA replication errors is compromised, leading to a state called MSI-High (MSI-H).

Why it is Ordered

This test is primarily ordered for patients diagnosed with colorectal, endometrial, or gastric cancers. It serves two main purposes: screening for Lynch Syndrome (a hereditary cancer predisposition) and determining eligibility for immunotherapy. Tumors that are MSI-High or MMR-deficient (dMMR) often respond exceptionally well to immune checkpoint inhibitors like pembrolizumab.

Associated Conditions

• Lynch Syndrome: An inherited condition that significantly increases the risk of various cancers.
• Colorectal Cancer: Roughly 15% of sporadic colorectal cancers are dMMR.
• Endometrial Carcinoma: MSI status helps in prognostic stratification.

Clinical Implications

Identifying a loss of protein expression guides the clinical team toward either further genetic germline testing or specific targeted oncological therapies. It provides vital information regarding the aggressiveness of the tumor and the potential success of the treatment plan.