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Microsatellite instability (MSI) is the end result of a defective mismatch repair (MMR) system and generally occurs as a result of a germline mutation in one of the MMR genes (hereditary) or as a result of methylation of the MLH1 promoter (sporadic). Microsatellites are repetitive sequences distributed throughout the genome that consist of nucleotide repeats (mono-, di- or higher order nucleotide repeats) that are often copied incorrectly by DNA polymerase. In tumors with mismatch repair defects, these expansions or contractions of the number of nucleotide repeats are not repaired, leading to the phenomenon of MSI. PCR is used to amplify specific microsatellite repeats within the genome and MSI is detected by comparing the length of nucleotide repeats in tumor cells versus normal cells. If the length of the repeat sequences from tumor versus normal differs in 2 or more of the 5 regions tested, microsatellite instability is present, and the specimen is characterized as MSI-high (MSI-H). Specimens showing differing lengths in 1 of the regions tested is characterized as MSI-low (MSI-L). If no differences are seen between the normal and tumor, the sample is considered microsatellite stable (MSS). Cases of hereditary non-polyposis colorectal carcinoma (HNPCC) or Lynch Syndrome and approximately 15% of sporadic colorectal carcinomas (CRC) exhibit defective MMR. In sporadic CRC, MSI is the result of acquired hypermethylation silencing of MLH1. In individuals/families in which HNPCC/Lynch syndrome is suspected, the presence of MSI in a tumor suggests a germline mutation in one of the MMR genes and further mutational testing should be considered. Colorectal carcinomas with defective DNA mismatch repair (MSI-high), have a better prognosis compared to those with intact mismatch repair (microsatellite stable or MSI-low).
Disease State: Mismatch Repair Genes - Correlates with MSI
CPT Code(s): 81301; 88381 may apply; G0452 may apply (reference only; CPTs may vary)
Turnaround Time: Within 5-8 business days of receipt
Both Tumor and Normal Required. 1) Formalin-fixed, paraffin-embedded (FFPE) tissue containing greater than 10% tumor - AND - 2) Formalin-fixed, paraffin-embedded (FFPE) tissue containing normal tissue OR normal peripheral blood (Preferred: 5 ml in EDTA (purple top) / Acceptable: 5 ml in sodium heparin (green top); transport with frozen ice pack)