Molecular Diagnostics

BJC Open article

British Journal of Cancer (2012) 107, 340–344. doi:10.1038/bjc.2012.218 www.bjcancer.com
Published online 22 May 2012

KRAS mutations in primary tumours and post-FOLFOX metastatic lesions in cases of colorectal cancer

Y Kawamoto1,2,3,4, K Tsuchihara2, T Yoshino3, N Ogasawara2, M Kojima5, M Takahashi3, A Ochiai5, H Bando3, N Fuse3, M Tahara3, T Doi3, H Esumi2, Y Komatsu4 and A Ohtsu3

  1. 1Department of Gastroenterology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
  2. 2Cancer Physiology Project, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, Japan
  3. 3Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, Japan
  4. 4Department of Cancer Center, Hokkaido University Hospital, Sapporo 060-8638, Japan
  5. 5Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa 277-8577, Japan

Correspondence: Dr K Tsuchihara, E-mail: ktsuchih@east.ncc.go.jp

Received 14 February 2012; Revised 25 April 2012; Accepted 29 April 2012
Advance online publication 22 May 2012

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Abstract

Background:

  

KRAS mutations are predictive markers for the efficacy of anti-EGFR antibody therapies in patients with metastatic colorectal cancer. Although the mutational status of KRAS is reportedly highly concordant between primary and metastatic lesions, it is not yet clear whether genotoxic chemotherapies might induce additional mutations.

Methods:

  

A total of 63 lesions (23 baseline primary, 18 metastatic and 24 post-treatment metastatic) from 21 patients who were treated with FOLFOX as adjuvant therapy for stage III/IV colorectal cancer following curative resection were examined. The DNA samples were obtained from formalin-fixed paraffin-embedded specimens, and KRAS, NRAS, BRAF and PIK3CA mutations were evaluated.

Results:

  

The numbers of primary lesions with wild-type and mutant KRAS codons 12 and 13 were 8 and 13, respectively. The mutational status of KRAS remained concordant between the primary tumours and the post-FOLFOX metastatic lesions, irrespective of patient background, treatment duration and disease-free survival. Furthermore, the mutational statuses of the other genes evaluated were also concordant between the primary and metastatic lesions.

Conclusion:

  

Because the mutational statuses of predictive biomarker genes were not altered by FOLFOX therapy, specimens from both primary tumours and post-FOLFOX tumour metastases might serve as valid sources of DNA for known genomic biomarker testing.

Keywords:

colorectal cancer; genomic biomarker; KRAS; anti-EGFR antibody; oxaliplatin