Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases

Georgios Karagkounis, Michael S. Torbenson, Hubert D. Daniel, Nilofer S. Azad, Luis A. Diaz, Ross C. Donehower, Kenzo Hirose, Nita Ahuja, Timothy M. Pawlik, Michael A. Choti

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Abstract

BACKGROUND Molecular biomarkers offer the potential for refining prognostic determinants in patients undergoing cancer surgery. Among patients with colorectal cancer, KRAS and BRAF are important biomarkers, but their role in patients undergoing surgical therapy for liver metastases is unknown. In this study, the incidence and prognostic significance of KRAS and BRAF mutations were determined in patients undergoing surgical therapy of colorectal liver metastases (CRLM). METHODS KRAS and BRAF analysis was performed on 202 patients undergoing surgery for CRLM between 2003 and 2008. Tumor samples were analyzed for somatic mutations using sequencing analysis (KRAS, codon12/13, BRAF, V600E). The frequency of mutations was ascertained, and their impact on outcome was determined relative to other clinicopathologic factors. RESULTS KRAS gene mutations were detected in 58/202 patients (29%). In contrast, mutation in the BRAF gene was identified in very low frequency in this surgical cohort, found in only 4/202 (2%) patients. On multivariate analysis, KRAS mutation was associated with worse survival (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.21-3.26), as well as recurrence risk (HR, 1.68; 95% CI, 1.04-2.70). Although other clinicopathologic features, including tumor number, carcinoembryonic antigen, and primary stage were also associated with survival, KRAS status remained independently predictive of outcome. The low incidence of BRAF mutation limited assessment of its prognostic impact. CONCLUSION Whereas KRAS mutations were found in approximately one third of patients, BFAF mutations were found in only 2% of patients undergoing surgery for CRLM. KRAS status was an independent predictor of overall and recurrence-free survival. Molecular biomarkers such as KRAS may help to refine our prognostic assessment of patients undergoing surgical therapy for CRLM.

Original languageEnglish (US)
Pages (from-to)4137-4144
Number of pages8
JournalCancer
Volume119
Issue number23
DOIs
StatePublished - Dec 1 2013

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Colorectal Surgery
Neoplasm Metastasis
Mutation
Liver
Incidence
Biomarkers
Survival
Confidence Intervals
Recurrence
Neoplasms
Carcinoembryonic Antigen
Mutation Rate
Genes
Colorectal Neoplasms
Therapeutics
Multivariate Analysis
Odds Ratio

Keywords

  • factors
  • hepatectomy
  • molecular
  • personalized therapy
  • predictors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Karagkounis, G., Torbenson, M. S., Daniel, H. D., Azad, N. S., Diaz, L. A., Donehower, R. C., ... Choti, M. A. (2013). Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer, 119(23), 4137-4144. https://doi.org/10.1002/cncr.28347

Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. / Karagkounis, Georgios; Torbenson, Michael S.; Daniel, Hubert D.; Azad, Nilofer S.; Diaz, Luis A.; Donehower, Ross C.; Hirose, Kenzo; Ahuja, Nita; Pawlik, Timothy M.; Choti, Michael A.

In: Cancer, Vol. 119, No. 23, 01.12.2013, p. 4137-4144.

Research output: Contribution to journalArticle

Karagkounis, G, Torbenson, MS, Daniel, HD, Azad, NS, Diaz, LA, Donehower, RC, Hirose, K, Ahuja, N, Pawlik, TM & Choti, MA 2013, 'Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases', Cancer, vol. 119, no. 23, pp. 4137-4144. https://doi.org/10.1002/cncr.28347
Karagkounis G, Torbenson MS, Daniel HD, Azad NS, Diaz LA, Donehower RC et al. Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer. 2013 Dec 1;119(23):4137-4144. https://doi.org/10.1002/cncr.28347
Karagkounis, Georgios ; Torbenson, Michael S. ; Daniel, Hubert D. ; Azad, Nilofer S. ; Diaz, Luis A. ; Donehower, Ross C. ; Hirose, Kenzo ; Ahuja, Nita ; Pawlik, Timothy M. ; Choti, Michael A. / Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. In: Cancer. 2013 ; Vol. 119, No. 23. pp. 4137-4144.
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title = "Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases",
abstract = "BACKGROUND Molecular biomarkers offer the potential for refining prognostic determinants in patients undergoing cancer surgery. Among patients with colorectal cancer, KRAS and BRAF are important biomarkers, but their role in patients undergoing surgical therapy for liver metastases is unknown. In this study, the incidence and prognostic significance of KRAS and BRAF mutations were determined in patients undergoing surgical therapy of colorectal liver metastases (CRLM). METHODS KRAS and BRAF analysis was performed on 202 patients undergoing surgery for CRLM between 2003 and 2008. Tumor samples were analyzed for somatic mutations using sequencing analysis (KRAS, codon12/13, BRAF, V600E). The frequency of mutations was ascertained, and their impact on outcome was determined relative to other clinicopathologic factors. RESULTS KRAS gene mutations were detected in 58/202 patients (29{\%}). In contrast, mutation in the BRAF gene was identified in very low frequency in this surgical cohort, found in only 4/202 (2{\%}) patients. On multivariate analysis, KRAS mutation was associated with worse survival (hazard ratio [HR], 1.99; 95{\%} confidence interval [CI], 1.21-3.26), as well as recurrence risk (HR, 1.68; 95{\%} CI, 1.04-2.70). Although other clinicopathologic features, including tumor number, carcinoembryonic antigen, and primary stage were also associated with survival, KRAS status remained independently predictive of outcome. The low incidence of BRAF mutation limited assessment of its prognostic impact. CONCLUSION Whereas KRAS mutations were found in approximately one third of patients, BFAF mutations were found in only 2{\%} of patients undergoing surgery for CRLM. KRAS status was an independent predictor of overall and recurrence-free survival. Molecular biomarkers such as KRAS may help to refine our prognostic assessment of patients undergoing surgical therapy for CRLM.",
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author = "Georgios Karagkounis and Torbenson, {Michael S.} and Daniel, {Hubert D.} and Azad, {Nilofer S.} and Diaz, {Luis A.} and Donehower, {Ross C.} and Kenzo Hirose and Nita Ahuja and Pawlik, {Timothy M.} and Choti, {Michael A.}",
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T1 - Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases

AU - Karagkounis, Georgios

AU - Torbenson, Michael S.

AU - Daniel, Hubert D.

AU - Azad, Nilofer S.

AU - Diaz, Luis A.

AU - Donehower, Ross C.

AU - Hirose, Kenzo

AU - Ahuja, Nita

AU - Pawlik, Timothy M.

AU - Choti, Michael A.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - BACKGROUND Molecular biomarkers offer the potential for refining prognostic determinants in patients undergoing cancer surgery. Among patients with colorectal cancer, KRAS and BRAF are important biomarkers, but their role in patients undergoing surgical therapy for liver metastases is unknown. In this study, the incidence and prognostic significance of KRAS and BRAF mutations were determined in patients undergoing surgical therapy of colorectal liver metastases (CRLM). METHODS KRAS and BRAF analysis was performed on 202 patients undergoing surgery for CRLM between 2003 and 2008. Tumor samples were analyzed for somatic mutations using sequencing analysis (KRAS, codon12/13, BRAF, V600E). The frequency of mutations was ascertained, and their impact on outcome was determined relative to other clinicopathologic factors. RESULTS KRAS gene mutations were detected in 58/202 patients (29%). In contrast, mutation in the BRAF gene was identified in very low frequency in this surgical cohort, found in only 4/202 (2%) patients. On multivariate analysis, KRAS mutation was associated with worse survival (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.21-3.26), as well as recurrence risk (HR, 1.68; 95% CI, 1.04-2.70). Although other clinicopathologic features, including tumor number, carcinoembryonic antigen, and primary stage were also associated with survival, KRAS status remained independently predictive of outcome. The low incidence of BRAF mutation limited assessment of its prognostic impact. CONCLUSION Whereas KRAS mutations were found in approximately one third of patients, BFAF mutations were found in only 2% of patients undergoing surgery for CRLM. KRAS status was an independent predictor of overall and recurrence-free survival. Molecular biomarkers such as KRAS may help to refine our prognostic assessment of patients undergoing surgical therapy for CRLM.

AB - BACKGROUND Molecular biomarkers offer the potential for refining prognostic determinants in patients undergoing cancer surgery. Among patients with colorectal cancer, KRAS and BRAF are important biomarkers, but their role in patients undergoing surgical therapy for liver metastases is unknown. In this study, the incidence and prognostic significance of KRAS and BRAF mutations were determined in patients undergoing surgical therapy of colorectal liver metastases (CRLM). METHODS KRAS and BRAF analysis was performed on 202 patients undergoing surgery for CRLM between 2003 and 2008. Tumor samples were analyzed for somatic mutations using sequencing analysis (KRAS, codon12/13, BRAF, V600E). The frequency of mutations was ascertained, and their impact on outcome was determined relative to other clinicopathologic factors. RESULTS KRAS gene mutations were detected in 58/202 patients (29%). In contrast, mutation in the BRAF gene was identified in very low frequency in this surgical cohort, found in only 4/202 (2%) patients. On multivariate analysis, KRAS mutation was associated with worse survival (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.21-3.26), as well as recurrence risk (HR, 1.68; 95% CI, 1.04-2.70). Although other clinicopathologic features, including tumor number, carcinoembryonic antigen, and primary stage were also associated with survival, KRAS status remained independently predictive of outcome. The low incidence of BRAF mutation limited assessment of its prognostic impact. CONCLUSION Whereas KRAS mutations were found in approximately one third of patients, BFAF mutations were found in only 2% of patients undergoing surgery for CRLM. KRAS status was an independent predictor of overall and recurrence-free survival. Molecular biomarkers such as KRAS may help to refine our prognostic assessment of patients undergoing surgical therapy for CRLM.

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KW - molecular

KW - personalized therapy

KW - predictors

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