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 Aug 7;105(15):1151-6.
doi: 10.1093/jnci/djt173. Epub 2013 Jul 22.

Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication

Paul Lochhead  1 , Aya Kuchiba, Yu Imamura, Xiaoyun Liao, Mai Yamauchi, Reiko Nishihara, Zhi Rong Qian, Teppei Morikawa, Jeanne Shen, Jeffrey A Meyerhardt, Charles S Fuchs, Shuji Ogino
Affiliations

Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication

Paul Lochhead et al. J Natl Cancer Inst. .

Abstract

BRAF mutation in colorectal cancer is associated with microsatellite instability (MSI) through its relationship with high-level CpG island methylator phenotype (CIMP) and MLH1 promoter methylation. MSI and BRAF mutation analyses are routinely used for familial cancer risk assessment. To clarify clinical outcome associations of combined MSI/BRAF subgroups, we investigated survival in 1253 rectal and colon cancer patients within the Nurses' Health Study and Health Professionals Follow-up Study with available data on clinical and other molecular features, including CIMP, LINE-1 hypomethylation, and KRAS and PIK3CA mutations. Compared with the majority subtype of microsatellite stable (MSS)/BRAF-wild-type, MSS/BRAF-mutant, MSI-high/BRAF-mutant, and MSI-high/BRAF-wild-type subtypes showed multivariable colorectal cancer-specific mortality hazard ratios of 1.60 (95% confidence interval [CI] =1.12 to 2.28; P = .009), 0.48 (95% CI = 0.27 to 0.87; P = .02), and 0.25 (95% CI = 0.12 to 0.52; P < .001), respectively. No evidence existed for a differential prognostic role of BRAF mutation by MSI status (P(interaction) > .50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Kaplan–Meier survival plots for colorectal cancer according to combined MSI/BRAF subgroup. A) Colorectal cancer–specific survival. B) Overall survival. Multi-group log-rank P values demonstrate statistically significant deviation of any one of the survival curves from the null hypothesis. MSI = microsatellite instability; MSS = microsatellite stable.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Vilar E, Tabernero J. Molecular dissection of microsatellite instable colorectal cancer. Cancer Discov. 2013;3(5);502–511 - PMC - PubMed
    1. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23(3):609–618 - PubMed
    1. Roth AD, Delorenzi M, Tejpar S, et al. Integrated analysis of molecular and clinical prognostic factors in stage II/III colon cancer. J Natl Cancer Inst. 2012;104(21):1635–1646 - PubMed
    1. Sinicrope FA, Foster NR, Yoon HH, et al. Association of obesity with DNA mismatch repair status and clinical outcome in patients with stage II or III colon carcinoma participating in NCCTG and NSABP adjuvant chemotherapy trials. J Clin Oncol. 2012;30(4):406–412 - PMC - PubMed
    1. Bertagnolli MM, Redston M, Compton CC, et al. Microsatellite instability and loss of heterozygosity at chromosomal location 18q: prospective evaluation of biomarkers for stages II and III colon cancer—a study of CALGB 9581 and 89803. J Clin Oncol. 2011;29(23):3153–3162 - PMC - PubMed

Publication types

Substances