Abstract 605: The clinical outcome of patients with FOXL2 402C->G mutation positive adult-type Granulosa Cell Tumor of the ovary - a population based study with analysis of tissue and plasma ctDNA
Notice bibliographique
Résumé
Abstract Adult-type Granulosa Cell Tumors (AGCTs) are rare ovarian neoplasms comprising of 5% of all ovarian cancers. The FOXL2 (C->G) C134W mutation has been identified in 95% of all AGCTs, making it a pathognomonic defining feature. The histological diagnosis of AGCT is challenging; false diagnoses have been reported in up to 30-50% of cases in historical series. AGCTs behave unpredictably, and recurrences occur in 30-60% of the patients. The clinical outcome of molecularly defined, FOXL2-mutation positive AGCTs remains unknown. We conducted a partially prospective, population-based study of 248 AGCT patients diagnosed or treated at Helsinki University Central Hospital, Finland, during 3/1956-10/2013. Clinical data were collected from hospital records and the causes of death from the Finnish Causes of Death registry. FOXL2 mutation was analyzed from DNA extracted from FFPE (n = 171), and fresh tumor tissue samples (n = 51). Histological diagnosis was re-evaluated in Helsinki, and differential diagnostic cases (n = 24) were subjected to a blinded histological review in Vancouver. Serial plasma samples (n = 120) were collected prospectively during 8/2007- 4/2013 from 37 AGCT patients. The extracted ctDNA was preamplified using the C134W FOXL2 Taqman primer/probe. Tissue and plasma DNA were analyzed with Raindance Raindrop digital PCR technology. Statistical analyses were performed with Kaplan-Meier, and comparison of ctDNA positivity to tumor diameter with oneway ANOVA using JMP software. Of the original cohort, 165 (74%) tumors were positive and 57 (26%) tumors were negative for the FOXL2 402C->G mutation. Upon pathological review, an alternate diagnosis was set for 35 mutation negative patients in the first review (Helsinki), and for 41 patients in the final review (Vancouver). The vast majority (n = 149, 90%) of the FOXL2 mutation positive AGCT patients were diagnosed at stage I. The 5-, 10, and 15-year disease-specific survival (DSS) rates were 99%, and 93%, and 89% for the FOXL2 positive AGCT patients, compared to 58%, 53%, and 51% for the FOXL2 wild-type/misdiagnosed other tumors (p<0.0001, log-rank test). 51 (31%) of the FOXL2 positive AGCT patients had a recurrence at a median time of 7.6 years (range 1-26 years) after the diagnosis. FOXL2 mutation was detected in the plasma of 17% (n = 8) of samples from patients with primary or recurrent AGCT. ctDNA FOXL2 mutation was more likely detected in patients with large tumors (p = 0.003). We have characterized the largest population based cohort of AGCT patients, and shown that the outcome of the patients with FOXL2 mutation positive AGCT was superior to those with original AGCT misdiagnosis. ctDNA is a promising tool to diagnose AGCT in a non-invasive manner. Testing FOXL2 mutation should be used as standard of care, especially in differential diagnostic cases. Citation Format: Anniina Färkkilä, Melissa K. McConechy, Winnie Yang,, Nirit Rozenberg, Noora Andersson, Leila Unkila-Kallio, Ralf Bützow, Blake Gilks, David G. Huntsman, Mikko Anttonen. The clinical outcome of patients with FOXL2 402C->G mutation positive adult-type Granulosa Cell Tumor of the ovary - a population based study with analysis of tissue and plasma ctDNA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 605. doi:10.1158/1538-7445.AM2015-605
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».