CTNNB1 exon 3 mutations occur in ~25–30% of endometrial carcinoma (EC), predominantly end...
Vista determinista de la entidad fuente YAML. La autoridad clínica sigue con los ID de fuente citados y estado de firma del revisor.
| ID | BMA-CTNNB1-ENDOMETRIAL |
|---|---|
| Tipo | Relevancia terapéutica |
| Situación | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Enfermedades | DIS-ENDOMETRIAL |
| Fuentes | SRC-ESGO-ENDOMETRIAL-2025 SRC-ESMO-ENDOMETRIAL-2022 SRC-NCCN-UTERINE-2025 |
Hechos relativos a la posibilidad de adoptar medidas
| Biomarcador | BIO-CTNNB1 |
|---|---|
| Variante | CTNNB1 exon 3 mutación activadora (S33C, S37F, T41A, S45P) en carcinoma endometrial; clase molecular NSMP; asociada con sobreexpresión L1CAM y alto riesgo de recurrencia a pesar de estadio bajo |
| Enfermedad | DIS-ENDOMETRIAL |
| El nivel de ESCAT | IIB |
| Combinaciones recomendadas | carboplatin AUC 5 + paclitaxel 175 mg/m² q3w × 6 cycles — adjuvant chemotherapy for CTNNB1-mutant FIGO IA-IB endometrioid EC reclassified to high-intermediate/high risk per ESGO/ESMO/ESTRO 2023 guidelines, vaginal brachytherapy (VBT) ± external beam RT — per risk stratification; CTNNB1 mutation upgrades VBT-only recommendation to CT consideration |
| Resumen de las pruebas | CTNNB1 exon 3 mutations occur in ~25–30% of endometrial carcinoma (EC), predominantly endometrioid histology within the NSMP (No Specific Molecular Profile) molecular class per TCGA/ESGO/ESMO classification. CTNNB1 mutation is a key risk-stratifier within NSMP/intermediate-risk EC: presence of CTNNB1 exon 3 mutation is associated with L1CAM (L1 cell adhesion molecule) overexpression, which is an independent predictor of lymphovascular invasion and distant metastasis even in FIGO stage I-II disease. PORTEC-3 subset analyses and ESGO/ESMO/ESTRO 2023 EC risk stratification: CTNNB1-mutant FIGO IA-IB endometrioid EC is reclassified to "high-intermediate risk" or "high risk" — warranting consideration of adjuvant chemotherapy (carboplatin/paclitaxel) rather than vaginal brachytherapy alone, which would be standard for low-risk NSMP. No CTNNB1-targeted therapy approved for EC. WNT pathway inhibitors (porcupine inhibitors such as WNT-974, OMP-54F28; tankyrase inhibitors) are in early-phase trials but not endometrial-specific. Nirogacestat (gamma-secretase inhibitor, FDA 2023 for desmoid tum... |
Notas
ESCAT IIB: CTNNB1 mutation is a validated prognostic biomarker in EC that modifies adjuvant treatment decisions for low-stage endometrioid disease. L1CAM IHC (>10% positive cells) is an acceptable surrogate if CTNNB1 molecular testing is unavailable — both identify the high-recurrence NSMP subgroup. Molecular classification workflow for all EC: (1) POLE mutation testing (ultramutated → best prognosis); (2) MMR IHC (dMMR → pembrolizumab); (3) p53 IHC (abnormal = serous-like → worst prognosis); (4) CTNNB1 exon 3 sequencing (NSMP high-risk reclassification). CTNNB1 mutation in the context of dMMR or p53-aberrant EC does not independently modify management — MMR and p53 status take precedence in those molecular classes.
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