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
. 2010 Feb;17(2):416-24.
doi: 10.1245/s10434-009-0713-0. Epub 2009 Oct 8.

KRAS mutation and microsatellite instability: two genetic markers of early tumor development that influence the prognosis of colorectal cancer

Garrett M Nash  1 , Mark Gimbel, Alfred M Cohen, Zhao-Shi Zeng, Mackevin I Ndubuisi, Daniel R Nathanson, Jurg Ott, Francis Barany, Philip B Paty
Affiliations

KRAS mutation and microsatellite instability: two genetic markers of early tumor development that influence the prognosis of colorectal cancer

Garrett M Nash et al. Ann Surg Oncol. 2010 Feb.

Abstract

Introduction: We examined two genetic markers established early in colorectal tumor development, microsatellite instability (MSI) and mutation of the KRAS proto-oncogene, to see if these genetic changes influence metastatic disease progression and survival.

Patients and methods: MSI and KRAS mutation status were assessed in 532 primary adenocarcinomas (stage I-IV) from patients treated by colon resection. Median follow-up was 4.1 years (range 0-13.3 years) overall, 5.4 years for survivors.

Results: MSI and KRAS mutation were detected in 12 and 36% of cases, respectively. MSI was more common in early-stage disease (I, 15%; II, 21%; III, 10%; IV, 2%; P = 0.0001). Prevalence of KRAS mutation did not vary with stage (I, 36%; II, 34%; III, 35%; IV, 40%; P = ns). Disease-specific survival was far superior for MSI tumors than for microsatellite stability (MSS) tumors (5-year survival 92 vs. 59%, P < 0.0001). KRAS mutation was a marker of poor survival (5-year survival 55 vs. 68%, P = 0.0002). Using Cox regression analysis MSI, KRAS mutation, and stage were strong independent predictors of survival in the entire patient population. A high-mortality group with MSS/KRAS-mutant tumors was identified within the stage I and II cohort.

Conclusions: MSI and KRAS mutation provide fundamental genetic signatures influencing tumor behavior across patient subsets and stages of tumor development.

PubMed Disclaimer

Figures

FIG. 1
FIG. 1
a Stage distribution of MSI (P < 0.0001) and KRAS. b Chisquare table of MSI and KRAS prevalence
FIG. 2
FIG. 2
Disease-specific survival for stage I–IV patients: a MSI versus MSS, b KRAS mutant versus wild type
FIG. 3
FIG. 3
Disease-specific survival by stage: a MSI versus MSS, b KRAS mutant (mut) versus Wild type (wt)
FIG. 4
FIG. 4
Disease-specific survival stratified by both genetic markers
FIG. 5
FIG. 5
Early-stage cancer stratified by MSS and mutant KRAS
See this image and copyright information in PMC

References

    1. Skibber J, Minsky B, Hoff P. Cancer of the colon. In: DeVita VT, Rosenberg SA, editors. Principles and practice of oncology. Lippincott Williams & Wilkins; Philadelphia: 2001.
    1. Chapuis PH, Fisher R, Dent OF, Newland RC, Pheils MT. The relationship between different staging methods and survival in colorectal carcinoma. Dis Colon Rectum. 1985;28:158–61. - PubMed
    1. Barillari P, de Angelis R, Valabrega S, Indinnimeo M, Gozzo P, Ramacciato G, et al. Relationship of symptom duration and survival in patients with colorectal carcinoma. Eur J Surg Oncol. 1989;15:441–5. - PubMed
    1. Robinson M, Hardcastle J. Should we be screening for colorectal cancer? Br Med Bull. 1998;54:807–821. - PubMed
    1. Culliford A, Paty P. Surgery of colon cancer. In: Saltz L, editor. Colorectal cancer: multimodality management. Blackwell; Oxford, UK: 2002.

Publication types

MeSH terms