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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 2/2010

01-02-2010 | Translational Research and Biomarkers

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

Authors: Garrett M. Nash, MD, Mark Gimbel, MD, Jinru Shia, MD, Daniel R. Nathanson, MD, MacKevin I. Ndubuisi, PhD, Zhao-Shi Zeng, MD, Nancy Kemeny, MD, Philip B. Paty, MD

Published in: Annals of Surgical Oncology | Issue 2/2010

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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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Metadata
Title
KRAS Mutation Correlates With Accelerated Metastatic Progression in Patients With Colorectal Liver Metastases
Authors
Garrett M. Nash, MD
Mark Gimbel, MD
Jinru Shia, MD
Daniel R. Nathanson, MD
MacKevin I. Ndubuisi, PhD
Zhao-Shi Zeng, MD
Nancy Kemeny, MD
Philip B. Paty, MD
Publication date
01-02-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 2/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0605-3

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