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Microsatellite instability (MSI) refers to the biochemical detection of frameshifted microsatellite sequences from genomic DNA. Genesis of MSI is due to defective DNA mismatch repair (MMR) that fails to correct post-DNA replicative slippage mistakes at microsatellites. Most of the estimated 100,000 genomic microsatellites are non-coding; however, ∼150-300 microsatellites are coding such that, when frameshifted during the pathogenesis of an MSI tumor, they can generate immunogenic neopeptide antigens that limit the growth of tumor and prolong patient survival. In addition to the immune reaction and longer survival, patients with MSI colorectal cancers tend to have poorly differentiated tumors with mucinous features that are located in the right colon. Patients with MSI tumors are more resistant to 5-fluorouracil-based adjuvant chemotherapy but may be responsive to PD-1 immune checkpoint blockade. Specific defects of MMR function not only drive MSI but also elevate microsatellite alterations at selected tetranucleotide repeats that may further modify patient outcome. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC), a relatively frequent tumor in industrialized countries, occurs as a result of several genetic changes. Microsatellite instability (MSI) is a molecular feature that facilitates acquisition of new mutations. MSI caused by alterations in mismatch repair (MMR) genes, genes responsible for repairing DNA mismatches caused by slippage of DNA polymerase, is observed in fifteen percent of CRCs. Lynch syndrome, the most common hereditary colon cancer-genetic syndrome, is responsible for up to 5 % of CRCs and has MSI as a characteristic. When CRC occurs, MSI testing is an important step in identifying patients with Lynch syndrome. Diagnosis of Lynch syndrome has medical implications for both the affected individual and his or her family members. In addition, MSI is a prognostic and predictive factor for cancer patients. As MSI and immunostaining of MMR proteins, which seem to be similar and complementary to MSI, become widely available in pathology laboratories, use of these tests for any newly diagnosed CRC will be an option worth considering. In this review, we focus on the issue of universal MSI screening of all CRCs, irrespective of patient age, to identify more Lynch syndrome cases than are identified by well-established clinical criteria alone. We describe the growing literature in this field and discuss the potential effects of this approach on both the individual and the health-care system. [ABSTRACT FROM AUTHOR]