Mismatch-repair immunohistochemistry earns its place twice over: it screens for Lynch syndrome and it predicts response to immune checkpoint inhibitors. Running the four-antibody panel — MLH1, PMS2, MSH2, MSH6 — on colorectal and endometrial cancers, and considering it more broadly, is established practice.
When MLH1 and PMS2 are lost together, reflex to BRAF V600E or MLH1 promoter methylation to separate sporadic from Lynch-associated loss before sending a patient for germline testing. Preserve a block so predictive testing is not blocked later, and make the result explicit on the report for the multidisciplinary team.
Treating MMR IHC as routine rather than on-request is one of the highest-yield standing habits in oncological pathology — one stain that answers an inherited-risk question and a treatment question at once.
- Run the four-antibody MMR panel (MLH1, PMS2, MSH2, MSH6) on colorectal and endometrial cancers as standard.
- On combined MLH1/PMS2 loss, reflex to BRAF V600E or MLH1 methylation before germline referral.
- Preserve tissue for later predictive testing and state the MMR result clearly on the report.
- Remember the result is both diagnostic (Lynch screening) and predictive (checkpoint-inhibitor response).
Why it matters
One inexpensive stain carries both Lynch screening and immunotherapy prediction, so omitting it costs twice.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for pathology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free