臨床病理学ジャーナル

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Microsatellite Instability (MSI) Testing in Extra-colonic Tumors

Sanam Husain and Lewis Allen Hassell

Faulty DNA repair due to defects in the mismatch repair genes results in microsatellite instability (MSI). Microsatellites are short tandem repeats that are present throughout the genome and are sensitive to errors during the cell cycle. Malfunctioning of the DNA repair mechanisms many occur as a result of germ line mutations in the MMR genes (MLH1, MSH2, PMS2 and MSH6) as in the autosomal dominant disorder Hereditary non-polyposis syndrome (HNPCC), also known as Lynch syndrome (LS) or due to hypermethylation of the MLH1 gene. LS is associated with Colorectal carcinoma (CRC) and extra-colonic malignancies including tumors of the endometrium, ovary, pancreas, urinary bladder, stomach, skin, biliary tract and the central nervous system. Early identification and management of such patients and their family members can significantly reduce morbidity and mortality associated with such tumors. Current literature suggests that MSI testing is important not only in the genetic context, but it also has prognostic and predictive value, as has been shown in treatment of CRC. Initial screening mechanisms such as the Amsterdam criteria and Bethesda guidelines were based on personal and family history. Since then various clinical prediction models have been developed that utilize clinical and pathologic features in the risk assessment of patients with MMR deficiency. However, due to the limitations in these screening methods, many institutions are moving towards universal screening of patients with CRC and endometrial carcinomas.In this review, we outline the rationale for and current methods of testing for MSI, along with their relative merits, and discuss the thorny question of screening criteria and who should be screened