Mismatch repair IHC is simple to order and easy to misread. Before reporting loss, confirm that internal controls — stromal cells, lymphocytes, normal epithelium — are clearly positive in the same area; loss without a working control is not loss.
Next, look at the pattern. MLH1 and PMS2 lost together, or MSH2 and MSH6 lost together, are the expected pairs. Isolated, patchy or subclonal loss, or weak staining after neoadjuvant treatment, should be reported descriptively and followed by MSI testing rather than called deficient outright.
- Confirm positive internal control staining in the same field
- Report paired loss explicitly: MLH1/PMS2 or MSH2/MSH6
- Describe unusual, patchy or subclonal patterns rather than forcing a call
- Recommend MLH1 promoter methylation testing for MLH1/PMS2 loss
- Recommend MSI testing when the IHC pattern is unusual
Why it matters
An MMR result now drives both immunotherapy eligibility and Lynch referral.
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