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KRAS Mutation Correlates With Accelerated Metastatic Progression in Patients With Colorectal Liver Metastases

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Observational studies of patients with primary colorectal cancer have identified KRAS mutation as a marker of poor prognosis. To examine more directly whether KRAS mutations are associated with accelerated metastatic progression, we evaluated KRAS mutation as well as Ki-67 expression in patients with colorectal liver metastases not treated with cetuximab.

Methods

KRAS mutation status was assessed in a series of resected or sampled colorectal liver metastases. In a subset of these tumors, Ki-67 antigen expression was assessed by immunohistochemical stains. Median follow-up after liver resection or biopsy was 2.3 years.

Results

KRAS mutation in the liver metastasis was detected in 27% of the 188 patients. High Ki-67 expression in the liver metastasis was identified in 62% of 124 patients analyzed. Both markers were associated with multiple liver metastases and shorter time interval to their detection. KRAS mutation and high Ki-67 expression were independent predictors of poor survival after colon resection (hazard ratio [HR] 1.9 [95% confidence interval (95% CI), 1.1–3.4], HR 2.6 [95% CI, 1.4–4.8], respectively). Tumors with high Ki-67 expression were less likely to be selected for liver resection, and KRAS mutation was independently associated with poor survival after liver resection (HR 2.4 [95% CI, 1.4–4.0]).

Conclusions

KRAS mutation is associated with more rapid and aggressive metastatic behavior of colorectal liver metastases. These data suggest an important role for KRAS activation in colorectal cancer progression and support continued efforts to develop KRAS pathway inhibitors for this disease.

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Acknowledgment

Supported by a grant from the National Cancer Institute (2 P01 CA65930-05A2) and by the philanthropy of Marie and William Bianco. We also acknowledge the contributions of William Gerald, MD (deceased).

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Authors and Affiliations

  1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Garrett M. Nash MD, Mark Gimbel MD, Daniel R. Nathanson MD, MacKevin I. Ndubuisi PhD, Zhao-Shi Zeng MD & Philip B. Paty MD

  2. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Jinru Shia MD

  3. Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Nancy Kemeny MD

Authors
  1. Garrett M. Nash MD
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  2. Mark Gimbel MD
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  3. Jinru Shia MD
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  4. Daniel R. Nathanson MD
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  5. MacKevin I. Ndubuisi PhD
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  6. Zhao-Shi Zeng MD
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  7. Nancy Kemeny MD
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  8. Philip B. Paty MD
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Correspondence to Philip B. Paty MD.

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Nash, G.M., Gimbel, M., Shia, J. et al. KRAS Mutation Correlates With Accelerated Metastatic Progression in Patients With Colorectal Liver Metastases. Ann Surg Oncol 17, 572–578 (2010). https://doi.org/10.1245/s10434-009-0605-3

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  • DOI: https://doi.org/10.1245/s10434-009-0605-3

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