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Annals of Surgical Oncology

, Volume 17, Issue 2, pp 572–578 | Cite as

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

  • Garrett M. Nash
  • Mark Gimbel
  • Jinru Shia
  • Daniel R. Nathanson
  • MacKevin I. Ndubuisi
  • Zhao-Shi Zeng
  • Nancy Kemeny
  • Philip B. Paty
Translational Research and Biomarkers

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.

Keywords

Liver Metastasis Liver Resection Cetuximab KRAS Mutation Colorectal Liver Metastasis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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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Copyright information

© Society of Surgical Oncology 2009

Authors and Affiliations

  • Garrett M. Nash
    • 1
  • Mark Gimbel
    • 1
  • Jinru Shia
    • 2
  • Daniel R. Nathanson
    • 1
  • MacKevin I. Ndubuisi
    • 1
  • Zhao-Shi Zeng
    • 1
  • Nancy Kemeny
    • 3
  • Philip B. Paty
    • 1
  1. 1.Department of SurgeryMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  2. 2.Department of PathologyMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.Department of MedicineMemorial Sloan-Kettering Cancer CenterNew YorkUSA

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