title: 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.affiliation: Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kandioler
authors.affiliation: Center for Medical Statistics, Informatics, and Intelligent Systems, Section for Clinical Biometrics, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Mittlböck
authors.affiliation: Department of Surgery/Surgical Research, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kappel
authors.affiliation: Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Puhalla
authors.affiliation: Department of Surgery, Hospital Barmherzige Brüder, 1020 Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Herbst
authors.affiliation: Institute for Pathology, Medical University of Graz, 8036 Graz, Austria.
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.affiliation: Department of Surgery/Surgical Research, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wolf
authors.affiliation: Department of Surgery, Hospital Barmherzige Brüder, 9300 St Veit/Glan, Austria.
authors.forename: Jörg
authors.initials: J
authors.lastname: Tschmelitsch
authors.affiliation: Department of Internal Medicine, Albert Schweitzer Clinic, 8020 Graz, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Schippinger
authors.affiliation: Department of Internal Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Steger
authors.affiliation: Department of Surgery, Hospital Oberpullendorf, 7350 Oberpullendorf, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Hofbauer
authors.affiliation: Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.
authors.forename: Hellmut
authors.initials: H
authors.lastname: Samonigg
authors.affiliation: Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Gnant
authors.affiliation: Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Bela
authors.initials: B
authors.lastname: Teleky
authors.affiliation: Department of Internal Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Irene
authors.initials: I
authors.lastname: Kührer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011446:Prospective Studies; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005472:Fluorouracil
keywords: 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