Abstract P1-07-10: Comparison of three commercial ER/PR assays on a single clinical outcome series.
Notice bibliographique
Résumé
Abstract Introduction: Adjuvant tamoxifen is the standard therapy for early stage hormone receptor+ breast cancers (BC). Estrogen receptor (ER) and progesterone receptor (PR) analysis is routinely performed by immunohistochemical (IHC) testing on BC specimens to assist in determining hormone receptor status and patient treatment. ER/PR IHC methodologies and guidelines have recently come under review. Many clinical laboratories have opted to use platform specific, ready-to-use (RTU) ER/PR assays provided by three companies: Dako, Leica and Ventana. While each of these companies are using antibodies that were validated on BC clinical outcome series, these platform specific RTU assays have never been directly compared using the same clinical outcome series. We present a systematic comparison of the three platform specific RTU ER/PR assays, using a retrospective BC cohort, to evaluate the concordance and reproducibility of the RTU ER/PR assays, and to assess the ability of the RTU ER assays to predict tamoxifen response. Methods: The Calgary Tamoxifen Cohort is a retrospective database containing demographic, clinical and pathological data for 820 BC patients diagnosed between 1985–2000 at the Tom Baker Cancer Centre (Calgary, Canada). Formalin-fixed paraffin-embedded tissue blocks were available for 511 patients, and replicate 0.6mm cores were taken and built into tissue microarrays (TMAs). The TMAs were stained using the platform specific assays on the DakoLink Plus, Ventana BenchMark Ultra, or Bond-III Leica autostainers. Slides were manually scored by the Allred method. Results: Ventana and Dako had the best concordance for ER (κ=0.90). Substantial agreement was seen for ER staining between Leica and Ventana (κ=0.79), and Dako and Leica (κ=0.66). Agreement was more consistent between the three platforms for PR staining (κ=0.78–0.82). Inter-observer reproducibility was evaluated for all three platforms between three observers: Dako ER (κ=0.80–0.92) and PR (κ=0.69–0.90); Leica ER (κ=0.67–0.83) and PR (κ=0.70–0.89); Ventana ER (κ=0.88–1.00) and PR (κ=0.78–0.94). TMAs were rescored and intra-observer agreement was calculated: Dako ER (κ=1.00) and PR (κ=0.98); Leica ER (κ=0.91) and PR (κ=0.94); Ventana ER (κ=1.00) and PR (κ=0.94). ER Allred scores were dichotomized using current standards and univariate analysis for 5-year disease free survival was performed. All platforms achieved significance with the logrank test and hazard ratio (HR) estimates (p < 0.0001). Cox models were also run to adjust for lymph node status, grade, size and HER2 status. ER status determined by Dako [HR=0.37(0.19–0.74), p = 0.005] and Ventana [HR=0.40(0.18–0.87), p = 0.021] maintained significance, while ER status determined by Leica [HR=0.61(0.31–1.20), p = 0.154] did not. Conclusions: Concordance between RTU assays demonstrated more variation for ER than PR. All assays showed substantial agreement for inter- and intra- observer reproducibility. Although ER RTU assays from all vendors performed as expected in univariate analysis, multivariate models demonstrated differences. Dako and Ventana appeared equivalent in the multivariate analysis, each providing prognostic information, whereas Leica did not achieve independence in this analysis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-07-10.
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 | 0,022 | 0,036 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,002 |
| Bibliométrie | 0,002 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».