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Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial

Tejpar, Sabine
Delorenzi, Mauro
Fiocca, Roberto
Klingbiel, Dirk
Dietrich, Daniel
Biesmans, Bart
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Published in Journal of clinical oncology. 2010, vol. 28, no. 3, p. 466-474
Abstract PURPOSE: Mutations within the KRAS proto-oncogene have predictive value but are of uncertain prognostic value in the treatment of advanced colorectal cancer. We took advantage of PETACC-3, an adjuvant trial with 3,278 patients with stage II to III colon cancer, to evaluate the prognostic value of KRAS and BRAF tumor mutation status in this setting. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tissue blocks (n = 1,564) were prospectively collected and DNA was extracted from tissue sections from 1,404 cases. Planned analysis of KRAS exon 2 and BRAF exon 15 mutations was performed by allele-specific real-time polymerase chain reaction. Survival analyses were based on univariate and multivariate proportional hazard regression models. RESULTS: KRAS and BRAF tumor mutation rates were 37.0% and 7.9%, respectively, and were not significantly different according to tumor stage. In a multivariate analysis containing stage, tumor site, nodal status, sex, age, grade, and microsatellite instability (MSI) status, KRAS mutation was associated with grade (P = .0016), while BRAF mutation was significantly associated with female sex (P = .017), and highly significantly associated with right-sided tumors, older age, high grade, and MSI-high tumors (all P < 10(-4)). In univariate and multivariate analysis, KRAS mutations did not have a major prognostic value regarding relapse-free survival (RFS) or overall survival (OS). BRAF mutation was not prognostic for RFS, but was for OS, particularly in patients with MSI-low (MSI-L) and stable (MSI-S) tumors (hazard ratio, 2.2; 95% CI, 1.4 to 3.4; P = .0003). CONCLUSION: In stage II-III colon cancer, the KRAS mutation status does not have major prognostic value. BRAF is prognostic for OS in MS-L/S tumors.
Keywords Adenocarcinoma/diagnosis/ genetics/pathologyAdolescentAdultAgedColonic Neoplasms/diagnosis/ genetics/pathologyFemaleHumansMaleMiddle AgedMutationPrognosisProspective StudiesProto-Oncogene Proteins/ geneticsProto-Oncogene Proteins B-raf/ geneticsYoung AdultRas Proteins/ genetics
PMID: 20008640
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Other version: http://jco.ascopubs.org/content/28/3/466.full.pdf+html
Research group Groupe Roth Arnaud (oncologie) (285)
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ROTH, Arnaud et al. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. In: Journal of Clinical Oncology, 2010, vol. 28, n° 3, p. 466-474. doi: 10.1200/JCO.2009.23.3452 https://archive-ouverte.unige.ch/unige:21268

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Deposited on : 2012-05-23

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