POPOVICI, Vlad, Eva BUDINSKÁ, Fred T BOSMAN, Sabine TEJPAR, Arnaud D ROTH and Mauro DELORENZI. Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer. BMC Cancer. LONDON: BIOMED CENTRAL LTD, 2013, vol. 13, No 439, p. 1-7. ISSN 1471-2407. Available from: https://dx.doi.org/10.1186/1471-2407-13-439.
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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
Original language English
Type of outcome Article in a journal
Field of Study 30200 3.2 Clinical medicine
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 3.319
RIV identification code RIV/00216224:14110/13:00069862
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1186/1471-2407-13-439
UT WoS 000325080000001
Keywords in English BRAF V600E mutation; Colorectal cancer; KRAS mutations; Stratified analysis; Survival analysis
Tags International impact, Reviewed
Changed by Changed by: Ing. Mgr. Věra Pospíšilíková, učo 9005. Changed: 15/4/2014 16:12.
Abstract
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.
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