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The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
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2013 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 108, no 10, 2153-2163 p.Article in journal (Refereed) Published
Abstract [en]

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 Umea 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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2013. Vol. 108, no 10, 2153-2163 p.
Keyword [en]
BRAF, colorectal cancer, KRAS, prognosis, Quadruple index
National Category
Cancer and Oncology Cell and Molecular Biology Surgery
Identifiers
URN: urn:nbn:se:umu:diva-76265DOI: 10.1038/bjc.2013.212ISI: 000319561300030OAI: oai:DiVA.org:umu-76265DiVA: diva2:635986
Available from: 2013-07-08 Created: 2013-07-08 Last updated: 2017-12-06Bibliographically approved

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Eklöf, VincyWikberg, Maria L.Edin, SofiaJonsson, Björn-AndersRutegård, JörgenPalmqvist, Richard

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Eklöf, VincyWikberg, Maria L.Edin, SofiaJonsson, Björn-AndersRutegård, JörgenPalmqvist, Richard
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PathologyDepartment of Surgical and Perioperative SciencesSurgery
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British Journal of Cancer
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