TP53 Mutational Status and Prediction of Benefit from Adjuvant 5-Fluorouracil in Stage III Colon Cancer Patients
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
Affiliations
Daniela Kandioler
Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria
Martina Mittlböck
Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Clinical Biometrics, Medical University of Vienna, 1090 Vienna, Austria
Sonja Kappel
Department of Surgery/Surgical Research, Medical University of Vienna, 1090 Vienna, Austria
Harald Puhalla
Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria
Friedrich Herbst
Department of Surgery, Hospital Barmherzige Brüder, 1020 Vienna, Austria
Cord Langner
Institute for Pathology, Medical University of Graz, 8036 Graz, Austria
Brigitte Wolf
Department of Surgery/Surgical Research, Medical University of Vienna, 1090 Vienna, Austria
Jörg Tschmelitsch
Department of Surgery, Hospital Barmherzige Brüder, 9300 St Veit/Glan, Austria
Walter Schippinger
Department of Internal Medicine, Albert Schweitzer Clinic, 8020 Graz, Austria
Günther Steger
Department of Internal Medicine, Medical University of Vienna, 1090 Vienna, Austria
Friedrich Hofbauer
Department of Surgery, Hospital Oberpullendorf, 7350 Oberpullendorf, Austria
Hellmut Samonigg
Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria
Michael Gnant
Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria
Bela Teleky
Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria
Irene Kührer
Department of Internal Medicine, Medical University of Vienna, 1090 Vienna, Austria
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.
