BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer
- PMID: 21285991
- PMCID: PMC3048210
- DOI: 10.1038/bjc.2011.19
BRAF mutation is a powerful prognostic factor in advanced and recurrent colorectal cancer
Abstract
Background: Activating mutation of KRAS and BRAF are focused on as potential prognostic and predictive biomarkers in patients with colorectal cancer (CRC) treated with anti-EGFR therapies. This study investigated the clinicopathological features and prognostic impact of KRAS/BRAF mutation in advanced and recurrent CRC patients.
Method: Patients with advanced and recurrent CRC treated with systemic chemotherapy (n=229) were analysed for KRAS/BRAF genotypes by cycleave PCR. Prognostic factors associated with survival were identified by univariate and multivariate analyses using the Cox proportional hazards model.
Results: KRAS and BRAF mutations were present in 34.5% and 6.5% of patients, respectively. BRAF mutated tumours were more likely to develop on the right of the colon, and to be of the poorly differentiated adenocarcinoma or mucinous carcinoma, and peritoneal metastasis. The median overall survival (OS) for BRAF mutation-positive and KRAS 13 mutation-positive patients was 11.0 and 27.7 months, respectively, which was significantly worse than that for patients with wild-type (wt) KRAS and BRAF (40.6 months) (BRAF; HR=4.25, P<0.001, KRAS13; HR=2.03, P=0.024). After adjustment for significant features by multivariate Cox regression analysis, BRAF mutation was associated with poor OS (HR=4.23, P=0.019).
Conclusion: Presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC. The KRAS13 mutation showed a trend towards poor OS in patients with advanced and recurrent CRC.
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References
-
- Andreyev HJ, Norman AR, Cunningham D, Oates JR, Clarke PA (1998) Kirsten ras mutations in patients with colorectal cancer: the multicenter ‘RASCAL’ study. J Natl Cancer Inst 90: 675–684 - PubMed
-
- Bazan V, Migliavacca M, Zanna I, Tubiolo C, Grassi N, Latteri MA, La Farina M, Albanese I, Dardanoni G, Salerno S, Tomasino RM, Labianca R, Gebbia N, Russo A (2002) Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype. Ann Oncol 13: 1438–1446 - PubMed
-
- Bennecke M, Kriegl L, Bajbouj M, Retzlaff K, Robine S, Jung A, Arkan MC, Kirchner T, Greten FR (2010) Ink4a/Arf and oncogene-induced senescence prevent tumor progression during alternative colorectal tumorigenesis. Cancer Cell 18: 135–146 - PubMed
-
- Benvenuti S, Sartore-Bianchi A, Di Nicolantonio F, Zanon C, Moroni M, Veronese S, Siena S, Bardelli A (2007) Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res 67: 2643–2648 - PubMed
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