TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients.

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.

• Authors: Daniela Kandioler, Martina Mittlböck, Sonja Kappel, Harald Puhalla, Friedrich Herbst, Cord Langner, Brigitte Wolf, Jörg Tschmelitsch, Walter Schippinger, Günther Steger, Friedrich Hofbauer, Hellmut Samonigg, Michael Gnant, Bela Teleky, Irene Kührer, p53 Research Group and the Austrian Breast and Colorectal Study Group (ABCSG)
• Journal: EBioMedicine (EBioMedicine) Vol. 2 Issue 8 Pg. 825-30 (Aug 2015) ISSN: 2352-3964 [Print] Netherlands
• PMID: 26425688 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• TP53 protein, human
• Tumor Suppressor Protein p53
• Fluorouracil

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Colonic Neoplasms (drug therapy, genetics, mortality)
• Disease-Free Survival
• Female
• Fluorouracil (administration & dosage)
• Humans
• Male
• Middle Aged
• Mutation
• Neoplasm Staging
• Prospective Studies
• Survival Rate
• Tumor Suppressor Protein p53 (genetics)