p53-aberrant (p53-abn) endometrial carcinoma defines the highest-risk molecular subgroup...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-TP53-IHC-ENDOMETRIAL |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-05-06 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-ENDOMETRIAL |
| Sources | SRC-ESMO-ESGO-ESTRO-ENDOMETRIAL-2023 SRC-NCCN-UTERINE-2025 |
Actionability Facts
| Biomarker | BIO-TP53-IHC |
|---|---|
| Variant | p53-aberrant IHC pattern: either (a) diffuse strong nuclear staining >80% of tumor cell nuclei (overexpression, missense surrogate) OR (b) complete absence of nuclear staining with intact internal controls — endothelium/stroma must stain positive (null pattern, nonsense/frameshift surrogate). Equivocal (heterogeneous, patchy <80% or wild-type-pattern) = p53-wildtype by IHC. Note: BIO-TP53-IHC (this entry) ≠ BIO-TP53-MUTATION — IHC is the clinical surrogate used in ESMO 2023 molecular subtyping; sequencing confirmation optional but not required for guideline application. |
| Disease | DIS-ENDOMETRIAL |
| ESCAT tier | IB |
| Recommended combinations | Carboplatin AUC5 + paclitaxel 175 mg/m² q3w x4-6 cycles ± concurrent EBRT (45 Gy) — PORTEC-3 chemoRT regimen, Sequential approach: EBRT 45 Gy → carboplatin/paclitaxel x4 (or vice versa per institutional preference), Vaginal brachytherapy (VBT) may be added for vaginal cuff coverage |
| Contraindicated monotherapy | RT alone (pelvic EBRT without chemotherapy) — inferior to chemoRT in p53-abn subgroup per PORTEC-3 subgroup analysis (HR 0.52 for FFS with chemoRT) |
| Evidence summary | p53-aberrant (p53-abn) endometrial carcinoma defines the highest-risk molecular subgroup per the ProMisE/TCGA/ESMO 2023 molecular classification (corresponding to "copy-number-high/serous-like" TCGA group). p53-abn tumors are typically high-grade, often serous or clear-cell histology, with the worst prognosis (5-yr OS ~55-60% in early-stage vs ~90% for POLE-ultramutated). PORTEC-3 (de Boer et al. Lancet 2019 / Oncology 2022 update): phase III RCT, 686 pts high-risk endometrial carcinoma; adjuvant chemoradiotherapy (cisplatin 45 Gy EBRT + carboplatin/paclitaxel x4 cycles) vs pelvic RT alone. Primary results: 5-yr failure-free survival 75.5% vs 68.6% (HR 0.71, p=0.022); 5-yr OS 81.4% vs 76.1% (HR 0.70, p=0.034). Molecular subgroup analysis (León-Castillo et al. JCO 2020): among p53-abn tumors (n=150), chemoRT benefit was largest — HR for FFS 0.52 (95% CI 0.30–0.89); whereas no benefit was observed in MMRd or NSMP subgroups. This biomarker-treatment interaction analysis is the primary evidence for ESMO 2023 escalation recommendation. ESMO-ESGO-ESTRO 2023 guidelines: p53-abn molecular s... |
Notes
ESCAT IB. p53-aberrant IHC pattern (not TP53 sequencing) is the clinical standard for molecular subtype assignment in the ESMO 2023 / ProMisE classification. This is distinct from BMA-TP53-MUT-ENDOMETRIAL (gene mutation level, ESCAT IIIB, no targeted therapy) — the IHC pattern's actionability is about treatment intensification (chemoRT over RT alone), not about a targeted agent. The 4-class molecular subtyping (POLE-ultramutated → best prognosis, MMR-deficient, NSMP, p53-abn → worst prognosis) is now required in all newly diagnosed endometrial carcinomas per ESMO 2023 and NCCN 2025. Testing priority: POLE sequencing first, then MMR IHC (MLH1/MSH2/MSH6/PMS2), then p53 IHC. Practical note: p53-abn IHC CANNOT be interpreted in the context of concurrent POLE mutation — POLE-ultramutated tumors are assigned regardless of p53 IHC (POLE overrides per ESMO hierarchy rule).
Used By
No reverse references found in the YAML corpus.