Evaluation of MT1XT20 Single Quasi-Monomorphic Mononucleotide Marker for characterizingMicrosatellite Instability in Persian Lynch Syndrome patients

Background Colorectal malignancies with high microsatellite instability (MSI-H), either hereditary (Lynchsyndrome) or sporadic, demonstrate betterprognosis, altered response to 5FU chemotherapy and altered operativeapproach. It is now recommended to perform MSI testing for all new cases of colorectal cancer regardless of beingcategorized as hereditary or sporadic. For MSI detection, immunohistochemistry or PCR-based protocols using acohort of various sets of STR markers are recommended. Here we aimed to evaluate a simplified protocol using justa single STR marker, MT1XT20 mononucleotide repeat, for detection of MSI in Lynch syndrome patients. Promegafive- marker MSI testing panel and Immunohistochemistry used as gold standard in conjunction of MT1XT20.Methods Colorectal patients with positive history of familial cancers were sorted out by evaluating their medicalrecords. Based on Amsterdam II criteria for Lynch syndrome 20 families were short listed. DNA extracted from theformalin fixed paraffin embedded tissues and their adjacent normal tissues resected from the index case in eachfamily. Extracted DNA was subjected to MT1XT20 mononucleotide marker and commercially available fivemarkers MSI testing kit (Promega, USA). IHC also was performed on tissue sections and the results were comparedwith PCR based techniques.Results Eight (40%), seven (35%) and five (25%) cases were MSI positive using Promega kit, IHC and MT1XT20respectively. Among the markers included in Promega kit, BAT26 marker showed instability in all 8 samples wasthe most instable marker (100%). NR24 and NR21 markers showed instability in 7 cases (87.5%), BAT25 andMONO 27 markers were instable in 6 (75%) and 5 (62.5%) specimens respectively.Conclusion Although MT1XT20 as standalone marker has already reported as valid single marker for MSI testingin CRC patients, but we couldn’t verify this in Iranian patients. Instead BAT26 among the markers included inPromega MSI testing kit was shown instability in all 8 MSI-H CRC samples. Therefore, it seems BAT26 could actwell as a single marker for MSI testing in Iranian CRC patients

کلیدواژه ها:

Lynch syndrome ، MSI ، IHC ، MT1XT20 ، Quasi-monomorphic Repeats