Microsatellite Instability (MSI)
Add Clarity to DNA Mismatch Repair Markers
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MLH-1
• Aids in identifying gene most likely responsible for MSI
• MLH1 expression may correlate with survival
• Loss of function is almost always coupled with concurrent loss of PMS2
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MSH2
• MSH2 binds to a mismatched DNA duplex
• Joined by a heterodimer of MLH1 and PMSH
• Loss of function manifests as absent IHC expression of MSH2 & MSH6
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MSH6
• MSH6 is a heterodimer of MSH2
• Predicts more MSH gene mutation than molecular method
• Isolated absence of protein suggests mutation in the MSH6 gene
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PMS2
• PMS2 forms a heterodimer with MLH1
• Isolated absence of protein indicates mutation in the PMS2 gene
• Endometrial carcinoma linked to defects in MLH1/PMS2 genes
Buy PMS2References:
1. Bellizzi, AM & Frankel WL. Adv Anat Pathol 2009;16:405 2. Shia, J. J Mol Diagn 2008;10:293 3. Backes, FJ, et al. Gynecologic Oncol 2009;114:486