J 2013

Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer

POPOVICI, Vlad, Eva BUDINSKÁ, Fred T BOSMAN, Sabine TEJPAR, Arnaud D ROTH et. al.

Basic information

Original name

Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer

Authors

POPOVICI, Vlad (642 Romania, guarantor, belonging to the institution), Eva BUDINSKÁ (703 Slovakia, belonging to the institution), Fred T BOSMAN (756 Switzerland), Sabine TEJPAR (56 Belgium), Arnaud D ROTH (756 Switzerland) and Mauro DELORENZI (756 Switzerland)

Edition

BMC Cancer, LONDON, BIOMED CENTRAL LTD, 2013, 1471-2407

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30200 3.2 Clinical medicine

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.319

RIV identification code

RIV/00216224:14110/13:00069862

Organization unit

Faculty of Medicine

DOI

UT WoS

000325080000001

Keywords in English

BRAF V600E mutation; Colorectal cancer; KRAS mutations; Stratified analysis; Survival analysis

Tags

International impact, Reviewed
Změněno: 15/4/2014 16:12, Ing. Mgr. Věra Pospíšilíková

Abstract

V originále

Background: The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population.Methods: We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05.Results: In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation.Conclusions: The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in others having limited prognostic value. However, in the subpopulations where it is prognostic, it represents a marker of much higher risk than previously considered. KRAS mutation status does not seem to represent a strong prognostic variable.