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[Cancer Research 65, 6063-6069, July 15, 2005]
© 2005 American Association for Cancer Research


Molecular Biology, Pathobiology, and Genetics

Poor Survival Associated with the BRAF V600E Mutation in Microsatellite-Stable Colon Cancers

Wade S. Samowitz1, Carol Sweeney2, Jennifer Herrick2, Hans Albertsen2, Theodore R. Levin3, Maureen A. Murtaugh2, Roger K. Wolff2 and Martha L. Slattery2

1 Department of Pathology, University of Utah Health Sciences Center; 2 Department of Family and Preventive Medicine, Health Research Center, Salt Lake City, Utah and 3 Kaiser Permanente Medical Center, Walnut Creek, California

Requests for reprints: Wade S. Samowitz, Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT 84132. Phone: 801-585-2556; Fax: 801-585-3831; E-mail: wade.samowitz{at}hsc.utah.edu.

The BRAF V600E mutation has been associated with microsatellite instability and the CpG island methylator phenotype (CIMP) in colon cancer. We evaluated a large population-based sample of individuals with colon cancer to determine its relationship to survival and other clinicopathologic variables. The V600E BRAF mutation was seen in 5% (40 of 803) of microsatellite-stable tumors and 51.8% (43 of 83) of microsatellite-unstable tumors. In microsatellite-stable tumors, this mutation was related to poor survival, CIMP high, advanced American Joint Committee on Cancer (AJCC) stage, and family history of colorectal cancer [odds ratio, 4.23; 95% confidence interval (95% CI), 1.65-10.84]. The poor survival was observed in a univariate analysis of 5-year survival (16.7% versus 60.0%; P < 0.01); in an analysis adjusted for age, stage, and tumor site [hazard rate ratio (HRR), 2.97; 95% CI, 2.05-4.32]; in stage-specific, age-adjusted analyses for AJCC stages 2 to 4 (HRR, 4.88, 3.60, and 2.04, respectively); and in Kaplan-Meier survival estimates for AJCC stages 2 to 4 (P < 0.01 for all three stages). Microsatellite-unstable tumors were associated with an excellent 5-year survival whether the V600E mutation was present or absent (76.2% and 75.0%, respectively). We conclude that the BRAF V600E mutation in microsatellite-stable colon cancer is associated with a significantly poorer survival in stages 2 to 4 colon cancer but has no effect on the excellent prognosis of microsatellite-unstable tumors.




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Copyright © 2005 by the American Association for Cancer Research.