Abstract 5150: An immunohistochemical survey of predictive biomarkers for immunotherapy in ampullary carcinoma identifies strata with unique prognostic signatures
Notice bibliographique
Résumé
Abstract Introduction: Carcinomas located in the ampulla of Vater are a low incidence malignancy. Therapeutic options for early stage disease largely consist of pancreaticoduodenectomy followed by adjuvant chemotherapy with or without radiation. We explored the localization of CD8 and CD3 positive cells in addition to PDL-1 staining and mismatch repair deficiency markers to gain insight into the potential applicability of immunotherapy for patients with this disease. Methods: Excess material from clinically diagnosed cases collected between 1997 - 2013 were used to construct a duplicate 0.6mm core tissue microarray (TMA). All cases were derived from the Vancouver Coastal Health Region. Immunohistochemical staining was performed with the following markers: CD8, CD3, PD-L1, and the mismatch repair (MMR) markers: MSH2, MSH6, MLH1 and PMS2. CD3 and CD8 were quantified using localization within the tissue. PD-L1 was considered positive with >1% of cells stating positive. MMR markers were confirmed using full section and cases with convincing loss of any MMR marker were considered MMR deficient. Univariable disease specific survival analysis was performed to identify unique prognostic signatures and contingency analysis was performed to identify co-expression of the aforementioned biomarkers. Results: Ninety-eight cases were evaluable for all markers. The median age of the cohort was 69 [41 - 84] years. Forty-two percent were female. Adjuvant chemotherapy was provided to 15% of patients with the remainder undergoing post-surgical observation. Almost 90% were pT3 or pT4 and 48% had regional lymph node metastasis. CD3+ T-cells were either localized in the tumor stroma only (59%) or in both the stroma and epithelial compartments (41%). CD8+ T-cells were principally located in the stroma (66%) and both the epithelial and stroma (24%). Ten percent of cases had no CD8+ T-cells. PD-L1 staining was found in 10% of cases. MMR deficiency was found in 5% of cases. Improved prognostic signatures were found for cases with CD3+ and CD8+ T-cells in both the epithelial and stromal compartments (p <= 0.02). A trend towards a negative prognostic signature was observed for MMR deficient cases and for PD-L1 positive cases. The only significant positive association between biomarkers was found for CD3+ and CD8+ in both the epithelial and stromal compartments. Conclusions: The results of this analysis suggest that enhancement of an immune response yielding an increase CD3+ and CD8+ T-cells in the epithelial compartment may have a beneficial effect on prognosis. The relative scarcity of MMR deficiency in this disease is within the expected prevalence supported by other studies. Further exploration of the potential role of immunotherapy in immune enhanced subgroups of ampullary cancers is warranted. Citation Format: Steve E. Kalloger, Joanna Karasinska, James Topham, Daniel J. Renouf, David F. Schaeffer. An immunohistochemical survey of predictive biomarkers for immunotherapy in ampullary carcinoma identifies strata with unique prognostic signatures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5150.
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) | 0,003 | 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 ».