Strong p53 Expression Is an Independent Predictor of Outcome in De Novo Diffuse Large B Cell Lymphoma (DLBCL) Treated with Either CHOP or CHOP-R.
Notice bibliographique
Résumé
Abstract Background: The addition of rituximab to CHOP (CHOP-R) chemotherapy has resulted in an improved outcome for patients with DLBCL and has recently been shown to diminish the prognostic impact of two recognized biomarkers, namely Bcl-2 and Bcl-6. In the CHOP era, p53 mutations in DLBCL were associated with an aggressive clinical course and shortened survival. Using immunohistochemistry and mutational analysis, p53 over-expression and mutational status were examined in a population-based cohort of DLBCL patients treated with CHOP or CHOP-R (Sehn et al, J Clin Oncol2005; 23: 5027–33). Method: We analyzed 155 patients from a total cohort of 292 patients based on available paraffin blocks with sufficient tissue for interpretable immunohistochemistry for all antigens. All were initial diagnostic biopsies of de novo DLBCL cases accrued between 1999 and 2002 at the BCCA. HIV+ patients or those with active secondary malignancies were excluded. Tissue microarrays (TMA) were built using duplicate 0.6mm cores from paraffin embedded formalin fixed (FFPE) diagnostic biopsies and stained with antibodies against CD10, Bcl-6, MUM1, Bcl-2, p53 and p21. DLBCL cases were assigned to GCB or non-GCB subgroups based on the method of Hans et al., Blood 103: 275–82 (2004). Strong nuclear expression of the p53 antibody (clone DO7) was defined as high intensity (3/3) expression in >50% of the malignant cells. The p53 gene mutational analysis was performed on this subset of cases with DNA extracted from FFPE samples using the AmpliChip™ p53 test (developed in Roche Molecular Systems, Inc.). Results: Patients were treated with either CHOP (n = 77) or CHOP-R (n = 78). Their clinical characteristics, including the IPI factors, were evenly matched. The two treatment cohorts represent consecutive eras of therapy and thus the median follow-up of living patients was 5.1 and 4.0 y for CHOP vs CHOP-R, respectively. Of the 155 patients, 75 had a GCB phenotype and 80 non-GCB, with similar distribution in both treatment groups. There were 19 strong p53-positive cases (19/155 or 12.3%). Ten p53-positive cases were GCB and 9 were non-GCB. All 19 strong p53-positive cases were negative for p21 expression and 16/17 analyzable cases had p53 mutations. Univariate analysis of the entire cohort (n = 155) revealed that both IPI and p53 expression were of prognostic importance (p < 0.0001). In multivariate analysis, strong p53 and IPI were independent predictors of OS (p = 0.005 and p < 0.0001, respectively). Importantly, when analyzed by treatment era, strong p53 expression remained significant in both CHOP (p=0.015) and CHOP-R groups (p=0.012). Conclusion: Strong p53 protein expression correlates with p53 mutations and is an independent prognostic factor for patients with DLBCL even when treated with CHOP-R. p53 mutations were found in both GCB and non-GCB subtypes. Importantly the prognostic impact of p53 is not diminished in the era of CHOP-R, identifying a subgroup of patients with inferior survival. Overall Survival for 155 DLBCL Based on p53 Status Overall Survival for 155 DLBCL Based on p53 Status
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 | 0,000 | 0,000 |
| 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 ».