Mismatch repair immunohistochemistry is interpreted as loss or retention, and both calls depend on the internal control being adequate. Normal adjacent epithelium, stromal cells and infiltrating lymphocytes should show unequivocal nuclear staining; if they do not, the run is uninterpretable and the correct report says so rather than calling loss.
The failure modes are fixation and edge artefact more often than antibody performance. A block that was thick, poorly fixed, or decalcified can lose nuclear signal across the whole section, and the periphery of a large block can under-stain while the centre is fine — so a tumour sitting at the edge can appear to have lost a protein it retains. Patchy or weak staining is not loss: a subclonal or heterogeneous pattern is a reason to repeat and to consider MLH1 promoter methylation testing, not to report deficiency.
Write what you assessed. A report that states the internal control was adequate, and which cells it was read in, is one that can be relied on later when a germline result does not match. One that simply says a protein is lost cannot be re-examined without going back to the slide.
- Confirm unequivocal nuclear staining in adjacent normal epithelium, stroma or lymphocytes before calling loss of any nuclear marker
- Report a run with an inadequate internal control as uninterpretable and repeat it, rather than calling loss
- Treat patchy, weak or subclonal staining as a reason to repeat, not as deficiency
- Consider edge and fixation artefact where a tumour at the block periphery appears to have lost staining the centre retains
- State in the report that the internal control was adequate and where it was assessed
Why it matters
A false call of protein loss sends a patient and their family down a germline testing pathway that the slide never supported.
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