- Design
- Single-institution retrospective case series
- Population
- 32 treatment-naive MMR-deficient prostatic adenocarcinomas
- Primary outcome
- Clinicopathological features and intertumoral MMR heterogeneity
- Effect
- Discordant MMR between foci in 8/14 (57%); Lynch syndrome in 5/15 tested
A single-institution series described 32 treatment-naive mismatch repair-deficient prostate cancers. Grade ranged from GG2 to GG5; 38% were GG5. Intraductal or cribriform carcinoma was present in 78%, including 78% of GG2 tumours. Loss was mainly MSH2/MSH6 (78%). Every case had a concordant MMR gene alteration on sequencing, 35% had homologous recombination repair alterations, and 5 of 15 germline-tested had Lynch syndrome.
The key finding: of 14 cases stained on more than one block, 8 (57%) had discordant MMR status between foci. Deficiency was always in the highest-grade focus, with retained staining in separate lower-grade foci. One biopsy core showed the same split within a single core.
A negative MMR stain on a lower-grade focus can therefore miss a deficient tumour, with consequences for immunotherapy eligibility and Lynch testing.
- Select the highest-grade focus for MMR immunohistochemistry.
- Think of MMR deficiency when cribriform or intraductal pattern is present, even at GG2.
- Refer MMR-deficient cases for germline testing — a third had Lynch syndrome.
- State in the report which focus was stained.
Why it matters
Staining the wrong focus can miss a deficiency that changes treatment and family screening.
Don't overread it
These are 32 selected MMR-deficient cases from one centre; the discordance rate in unselected tumours is unknown.
The statistics, in plain English
Eight of 14 is 57%, but the 14 were cases where multiple blocks were stained, which may not represent all tumours. The consistent pattern — deficiency always in the highest grade — is more informative than the exact percentage.
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