![]() MSI-H (as determined by PCR-based assays or NGS) or dMMR (as determined by IHC) are recognized as predictive biomarkers for these therapies. Some biomarkers, such as PD-1 expression, are accurate in predicting the response to immunotherapy in certain cancer types (7). Tumors expressing these proteins are effective at priming an immune response and are subsequently susceptible to immunotherapies, such as immune checkpoint inhibitor therapies.įor the most effective use of immunotherapy, it is important to identify accurate biomarkers that can be used to predict susceptibility. When mistakes in DNA replication go uncorrected in cancer cells, they produce “foreign” proteins, called mutation-associated neoantigens (MANA), which can be detected by the immune system. Immune checkpoint inhibitor therapies targeting proteins such as PD-1 have revolutionized cancer treatment options, successfully treating certain cancers (2). Interest in MSI has exploded in recent years, driven by the discovery that its presence in tumor tissue can be predictive of a positive response to anti-PD-1 immunotherapies (4,5). In some cancers, the presence of MSI predicts a good immunotherapeutic response, and can be used to inform treatment decisions (6). Therefore, tumors with high-frequency MSI (MSI-H) are more effective at priming an immune response. Tumors with dMMR demonstrate an increased number of mutations (hypermutation) and an increase in the predicted number of new antigens appearing because of these mutations (4,5). The functional deficiency within one or more major DNA mismatch repair proteins (dMMR) that causes MSI also results in genetic instability and is closely related to the carcinogenicity of tumors (3). ![]() The results of these tests can indicate whether more specific genetic testing for Lynch syndrome should be performed. MSI analysis is used along with immunohistochemistry (IHC) as a screening test to determine if Lynch syndrome is likely. In addition to colorectal cancer, Lynch syndrome is associated with several other cancers including endometrial, ovarian and stomach cancer. Lynch syndrome is caused by mutations to the major DNA mismatch repair genes. Microsatellite instability (MSI) has been linked to cancer since 1993 when its association with Lynch syndrome, a hereditary nonpolyposis colon cancer, was first reported (1,2). ![]()
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