Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 May 28;108(10):2153-63.
doi: 10.1038/bjc.2013.212. Epub 2013 May 9.

The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer

V Eklöf  1 , M L Wikberg, S Edin, A M Dahlin, B-A Jonsson, Å Öberg, J Rutegård, R Palmqvist
Affiliations

The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer

V Eklöf et al. Br J Cancer. .

Abstract

Background: Mutations in KRAS, BRAF, PIK3CA and PTEN expression have been in focus to predict the effect of epidermal growth factor receptor-blocking therapy in colorectal cancer (CRC). Here, information on these four aberrations was collected and combined to a Quadruple index and used to evaluate the prognostic role of these factors in CRC.

Patients: We analysed the mutation status in KRAS, BRAF and PIK3CA and PTEN expression in two separate CRC cohorts, Northern Sweden Health Disease Study (NSHDS; n=197) and Colorectal Cancer in Umeå Study (CRUMS; n=414). A Quadruple index was created, where Quadruple index positivity specifies cases with any aberration in KRAS, BRAF, PIK3CA or PTEN expression.

Results: Quadruple index positive tumours had a worse prognosis, significant in the NSHDS but not in the CRUMS cohort (NSHDS; P=0.003 and CRUMS; P=0.230) in univariate analyses but significance was lost in multivariate analyses. When analysing each gene separately, only BRAF was of prognostic significance in the NSHDS cohort (multivariate HR 2.00, 95% CI: 1.16-3.43) and KRAS was of prognostic significance in the CRUMS cohort (multivariate HR 1.48, 95% CI: 1.02-2.16). Aberrations in PIK3CA and PTEN did not add significant prognostic information.

Conclusions: Our results suggest that establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in CRC.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The interrelationship between cases with mutations in KRAS, BRAF, PIK3CA and loss of PTEN expression in the NSHDS and the CRUMS cohorts. Total number of aberrations in NSHDS (A); KRAS (N=30), BRAF (N=31), PIK3CA (N=3), PTEN (N=18); CRUMS (B); KRAS (N=77), BRAF (N=50), PIK3CA (N=8), PTEN (N=57). Patients with missing value in any of the marker were excluded from the Figure.
Figure 2
Figure 2
Cancer-specific survival analyses with respect to the Quadruple index and the KRAS, BRAF, PIK3CA and loss of PTEN expression separately.
Figure 3
Figure 3
Cancer-specific survival analyses in the NSHDS and the CRUMS, stratified for KRAS or BRAF mutations, in relation to MSI screening status and CIMP status.
See this image and copyright information in PMC

References

    1. Ahuja N, Mohan AL, Li Q, Stolker JM, Herman JG, Hamilton SR, Baylin SB, Issa JP. Association between CpG island methylation and microsatellite instability in colorectal cancer. Cancer Res. 1997;57:3370–3374. - PubMed
    1. Amado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626–1634. - PubMed
    1. Barault L, Charon-Barra C, Jooste V, de la Vega MF, Martin L, Roignot P, Rat P, Bouvier AM, Laurent-Puig P, Faivre J, Chapusot C, Piard F. Hypermethylator phenotype in sporadic colon cancer: study on a population-based series of 582 cases. Cancer Res. 2008;68:8541–8546. - PubMed
    1. Bardelli A, Siena S. Molecular mechanisms of resistance to cetuximab and panitumumab in colorectal cancer. J Clin Oncol. 2010;28:1254–1261. - PubMed
    1. Benlloch S, Paya A, Alenda C, Bessa X, Andreu M, Jover R, Castells A, Llor X, Aranda FI, Massuti B. Detection of BRAF V600E mutation in colorectal cancer: comparison of automatic sequencing and real-time chemistry methodology. J Mol Diagn. 2006;8:540–543. - PMC - PubMed

Publication types

MeSH terms