Usefulness of immunohistochemistry and microsatellite instability in families with suspected Lynch syndrome: F07

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Aim:The study aimed to select patients suspicious of Lynch syndrome (LS) for genetic studies to identify MLH1, MSH2 and MSH6, microsatellite instability (MSI) and to use immunohistochemistry (IHC) to identifyproteins derived from MLH1, MSH2 and MSH6 to assess their value aspredictive markers.Method:Thirty-eight families with suspected LS (21 Amsterdam/17 Bethesda) were selected. They were studied by MSI, IHC for MLH1, MSH2 and MSH6 mutations in the tumour, and MLH1, MSH2 and MSH6 by SSCP sequencing and MLPA techniques.Results:Genetic analysis showed mutations in 19/38 families (11 in MLH1, 6 in MSH2 and 2 in MSH6). In families fulfilling the Amsterdam criteria, mutations were detected in 16/21 (76%). MSI was positive in all 19 families with an identified mutation (18 MSI-H, 1 MSI-L). IHC for the mutated gene correlated in 15/19 (79%) patients. Among patients without an identified mutation, 12 had MSIpositive phenotype, and 7 showed a loss of MLH1 or MSH6 expression.Conclusion:MSI appeared to be a more reliablepredictive marker for mutations in MLH1, MSH2 and MSH6 than IHC. The study was supported by FONDECYT 1040827, Cleveland Clinic Foundation, and Clinica Las Condes.

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