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

Kandioler D, Mittlböck M, Kappel S, Puhalla H, Herbst F, Langner C, Wolf B, Tschmelitsch J, Schippinger W, Steger G, Hofbauer F, Samonigg H, Gnant M, Teleky B, Kührer I, p53 Research Group and the Austrian Breast and Colorectal Study Group (ABCS - EBioMedicine (2015)

Bottom Line: A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095).In the N2 category, the TP53 status did not affect survival (P = 0.4992).TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria.

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.

No MeSH data available.


Related in: MedlinePlus

(A,B): Kaplan–Maier estimates of cumultative survival by TP53 status (A) in N1 patients (B) in N2 patients.
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f0005: (A,B): Kaplan–Maier estimates of cumultative survival by TP53 status (A) in N1 patients (B) in N2 patients.

Mentions: In N1 patients, the five-year overall survival was 81.0% for TP53 wildtype patients compared to 62.0% in TP53 mutant patients (HR = 2.131 (95 % CI: 1.344–3.378); P = 0.0010) (Fig. 1A). In N2 patients, the TP53 status did not affect the overall survival (P = 0.4992). The five-year overall survival was 66.3% for TP53 wildtype patients and 69.3% for mutant patients (HR = 0.834 (95% CI: 0.493–1.412)) (Fig. 1B).


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

Kandioler D, Mittlböck M, Kappel S, Puhalla H, Herbst F, Langner C, Wolf B, Tschmelitsch J, Schippinger W, Steger G, Hofbauer F, Samonigg H, Gnant M, Teleky B, Kührer I, p53 Research Group and the Austrian Breast and Colorectal Study Group (ABCS - EBioMedicine (2015)

(A,B): Kaplan–Maier estimates of cumultative survival by TP53 status (A) in N1 patients (B) in N2 patients.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4563117&req=5

f0005: (A,B): Kaplan–Maier estimates of cumultative survival by TP53 status (A) in N1 patients (B) in N2 patients.
Mentions: In N1 patients, the five-year overall survival was 81.0% for TP53 wildtype patients compared to 62.0% in TP53 mutant patients (HR = 2.131 (95 % CI: 1.344–3.378); P = 0.0010) (Fig. 1A). In N2 patients, the TP53 status did not affect the overall survival (P = 0.4992). The five-year overall survival was 66.3% for TP53 wildtype patients and 69.3% for mutant patients (HR = 0.834 (95% CI: 0.493–1.412)) (Fig. 1B).

Bottom Line: A significant interaction between TP53 status, outcomes and nodal category was found (P = 0.0095).In the N2 category, the TP53 status did not affect survival (P = 0.4992).TP53 was not predictive in N2 patients, in whom 5FU is known to have no effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Medical University of Vienna, 1090 Vienna, Austria.

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.

No MeSH data available.


Related in: MedlinePlus