Abstract 4542: Development of a one-step molecular classifier for endometrial carcinoma using an amplicon-based gene panel and next generation sequencing technology
Notice bibliographique
Résumé
Abstract Objectives: Molecular classification of endometrial carcinoma (EC) is now recommended by the WHO, ESGO/ESTRO/ESP and NCCN guidelines. The pragmatic molecular classification tool, ProMisE, identifies four molecular subtypes based on next generation sequencing (NGS) for the detection of somatic pathogenic POLE mutations, and immunohistochemistry for mismatch repair and p53 proteins. ProMisE provides valuable prognostic and predictive information to direct care, however, multiple molecular results are often received from different time periods and/or from different centers which can cause delays. Therefore, we developed a classifier that relies on a single DNA-based NGS test with the goal of recapitulating the prognostic value of ProMisE by producing concordant results. Methods: Formalin fixed paraffin embedded (FFPE) EC tumor DNA was sequenced using the clinically validated Imagia Canexia Health Find ItTM amplicon-based next generation sequencing gene panel assay. The 38 gene panel assessed single nucleotide variants (SNVs), indels (insertions and deletions), gene amplification and microsatellite instability (MSI) using 21 MSI loci. To compare to the original ProMisE classifier, we identified somatic mutations in POLE, TP53 and MSI-High or MS-Stable for molecular classification. Molecular subtypes assigned by both classifiers were assessed for concordance metrics and Kaplan-Meier survival curves. Results: The one-step NGS molecular classifier assessed 165 unique patient FFPE EC samples that had previously been assessed by ProMisE. There were 152/165 cases that were concordant between molecular subtype assignment from the original ProMisE and the one-step NGS assay with a kappa statistic of 0.88 and accuracy of 0.92. There were 13 samples that were discordant (original classifications: 3 POLE, 3 MMRd, 2 p53abn, 5 NSMP/p53wt), which will be reviewed in detail. Results were concordant in 14 of 15 cases (93%) when both diagnostic biopsy and hysterectomy specimens were tested. Molecular subtypes maintained their associations with clinical outcomes (progression free survival, disease specific survival, overall survival). Conclusion: The one-step NGS molecular classifier demonstrates high concordance with the original ProMisE classifier including between biopsy and hysterectomy samples. This shows that reliable molecular testing could be obtained from time of first diagnosis. Prognostic value of this new one-step classification tool is maintained. Appropriate interpretation of results is critical, including limiting POLE mutation assignment to a confirmed list of pathogenic mutations and correct order of segregation for ECs with more than one molecular feature. Further validation is needed in a larger cohort to implement into standard of care testing. Citation Format: Melissa K. McConechy, Amy Jamieson, Amy Lum, Samuel Leung, Adrian Kense, Sonal Brahmbhatt, Ka Mun Nip, Ebru Baran, Dilmi Perera, Kurt Yakimovich, Ruth Miller, C. Blake Gilks, David Huntsman, Jessica N. McAlpine. Development of a one-step molecular classifier for endometrial carcinoma using an amplicon-based gene panel and next generation sequencing technology. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4542.
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 | 0,002 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,001 |
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 ».