期刊
EBIOMEDICINE
卷 2, 期 8, 页码 825-830出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2015.06.003
关键词
TP53; Predictive biomarker; Stage III colon cancer; Adjuvant 5-fluorouracil; Varying treatment efficacy
资金
- Medical Scientific Fund of the Mayor of the Capital City of Vienna [2093, 2297]
- Anniversary Fund of the Oesterreichische Nationalbank [8916, 12557]
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. (C) 2015 The Authors. Published by Elsevier B.V.
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