FOXL2 p.C134W (c.402C>G) is the defining molecular marker of adult granulosa cell tumor (...
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | BMA-FOXL2-GRANULOSA-CELL |
|---|---|
| Тип | Клінічна застосовність |
| Статус | переглянуто 2026-05-04 | очікує клінічного підпису | потрібне рев’ю клінічної застосовності |
| Хвороби | DIS-GRANULOSA-CELL |
| Джерела | SRC-CIVIC SRC-ESMO-OVARIAN-2024 SRC-NCCN-OVARIAN-2025 |
Дані про клінічну застосовність
| Біомаркер | BIO-FOXL2 |
|---|---|
| Варіант | FOXL2 p.C134W (c.402C>G) — present in ~97% of adult granulosa cell tumors; pathognomonic diagnostic marker; no FDA-approved targeted therapy as of 2026 |
| Хвороба | DIS-GRANULOSA-CELL |
| Рівень ESCAT | IIB |
| Рекомендовані комбінації | BEP (bleomycin 30 U IV day 1/8/15 + etoposide 100 mg/m² IV days 1–5 + cisplatin 20 mg/m² IV days 1–5 per 21-day cycle) — standard for advanced/recurrent AGCT, carboplatin AUC 5 + paclitaxel 175 mg/m² q3w — alternative for BEP-ineligible, leuprolide 3.75 mg IM q4w (or 11.25 mg q3m) — hormonal therapy for recurrent AGCT (off-label), palbociclib 125 mg PO QD (days 1–21) + letrozole 2.5 mg QD (28-day cycles) — investigational; FOXL2 C134W mutation may predict CDK4/6 inhibitor sensitivity |
| Підсумок доказів | FOXL2 p.C134W (c.402C>G) is the defining molecular marker of adult granulosa cell tumor (AGCT), present in ~97% of cases and essentially absent in other ovarian tumors (100% positive predictive value when confirmed). The mutation distinguishes AGCT from: (1) Juvenile GCT (FOXL2 wild-type); (2) Other sex cord-stromal tumors (Sertoli-Leydig, fibroma, thecoma); (3) Poorly differentiated carcinomas mimicking AGCT. Therapeutic targets: no FDA/EMA-approved targeted therapy for FOXL2 C134W as of 2026. Investigational: (a) CDK4/6 inhibitors (palbociclib, ribociclib) — phase II trials (NCT03462186 palbociclib in GCT); (b) Olaparib (PARP inhibitor) in BRCA-wild-type GCT (Mirvetuximab + olaparib combination); (c) Bevacizumab (anti-VEGF) — phase II activity ~14%; (d) Hormonal therapies (leuprolide, megestrol, anastrozole) — common in clinical practice for recurrent disease (response rates 20–30%) but no prospective phase III data. BEP chemotherapy (bleomycin/etoposide/cisplatin) or carboplatin/paclitaxel for advanced/relapsed disease. ESCAT IIB: diagnostic and monitoring utility established; th... |
Нотатки
ESCAT IIB: FOXL2 C134W is a diagnostic biomarker with emerging predictive utility. Clinical use: (1) Diagnosis — FOXL2 testing should be part of workup for any suspected AGCT; (2) ctDNA monitoring — FOXL2 C134W in plasma ctDNA detects subclinical relapse (AGCT recurs at median 10–15 years post-diagnosis; serial ctDNA surveillance is under investigation); (3) Therapeutic target — clinical trials with CDK4/6 inhibitors actively enrolling (refer patients to NCT03462186 or institutional protocols). Inhibin B and AMH are serum markers used for AGCT monitoring (not FOXL2-specific but clinically useful). Staging surgery (BSO + peritoneal staging) is curative for early-stage disease (stage I; 90% 10-yr OS). Fertility-sparing surgery (unilateral SO) may be considered for young patients with stage IA disease.
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