A 55-year-old postmenopausal woman has endometrial carcinoma with microsatellite instability (MSI-H), POLE mutation, and TP53 wild-type. According to the ProMisE molecular classification of endometrial carcinoma, which group does this tumor belong to, and what is the prognostic implication?

• A MMRd (mismatch repair deficient) — intermediate prognosis
• B NSMP (no specific molecular profile) — intermediate prognosis
• C p53abn (TP53 abnormal) — worst prognosis
• D POLE (ultramutated) — most favorable prognosis ✓

Explanation

The ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) molecular classification divides endometrial carcinomas into four groups: POLE-ultramutated (best prognosis), MMRd-mismatch repair deficient (intermediate), NSMP-no specific molecular profile (intermediate), and p53abn (worst prognosis/serous-like). POLE-mutated (exonuclease domain mutations in POLE) endometrial carcinomas have an ultramutated phenotype with an exceptional prognosis even when high-grade, due to a high neo-antigen load provoking strong immune surveillance. A tumor with POLE mutation takes classification precedence over MSI-H in the ProMisE hierarchy; even if MSI-H is present, POLE classification supersedes MMRd.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.