A 42-year-old woman with endometrial carcinoma is found to have mismatch repair deficiency (dMMR) on immunohistochemistry showing loss of MSH2 and MSH6. This molecular subtype corresponds to which TCGA endometrial cancer classification?
- A POLE ultramutated (ProMisE subtype 1)
- B Microsatellite instability-high (MSI-H) ✓
- C Copy-number low (endometrioid-like, no specific molecular profile)
- D Copy-number high (serous-like, TP53 mutant)
Correct answer: B. Microsatellite instability-high (MSI-H)
Explanation
The TCGA classification divides endometrial carcinomas into four molecular subtypes: POLE ultramutated (best prognosis), MSI-H/dMMR (intermediate-good prognosis, Lynch syndrome association), copy-number low (no specific molecular profile, intermediate prognosis), and copy-number high/serous-like (TP53 mutation, worst prognosis). Loss of MSH2/MSH6 (or MLH1/PMS2) on IHC indicates dMMR corresponding to MSI-H subtype. POLE mutations are identified by sequencing exonuclease domain hotspots, not IHC.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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