TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients.
EBioMedicine
; 2(8): 825-30, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-26425688
ABSTRACT
We investigated the hypothesis that the varying treatment efficacy of adjuvant 5-fluorouracil (5FU) in stage III colon cancer is linked to the TP53 mutational status. ABCSG-90 was a prospective randomized trial in which effect of adjuvant 5FU was studied in stage III colon cancer patients. Tumor material of 70% of these patients (389/572) was available for analysis of the biomarker TP53 using a TP53-gene-specific Sanger sequencing protocol. Median follow-up was 88 months. TP53 mutation frequency was 33%. A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095). In the N1 category, TP53 wildtype patients had significantly better overall survival than TP53 mutated (81.0% vs. 62.0% overall survival at 5 years; HR = 2.131; 95% CI 1.344-3.378; P = 0.0010). In the N2 category, the TP53 status did not affect survival (P = 0.4992). In TP53 wildtype patients, the prognostic significance of N category was significantly enhanced (P = 0.0002). In TP53 mutated patients, survival curves of N1 and N2 patients overlapped and nodal category was no longer prognostic. The biomarker TP53 independently predicted effect of adjuvant 5FU in N1 colon cancer patients. TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.
Palavras-chave
5FU, 5-fluorouracil; ABCSG, Austrian Breast and Colorectal Cancer Study Group; Adjuvant 5-fluorouracil; CI, confidence intervals; FFPE, formalin-fixed paraffin-embedded; HR, hazard ratios; INF, interferon; LEV, levamisole; Predictive biomarker; Stage III colon cancer; TP53; Varying treatment efficacy
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Proteína Supressora de Tumor p53
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Neoplasias do Colo
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Fluoruracila
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Mutação
Tipo de estudo:
Clinical_trials
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Guideline
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Observational_studies
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Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article