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KRAS and BRAF Mutational Status in Primary Colorectal Tumors and Related Metastatic Sites: Biological and Clinical Implications

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

Abstract

Background

KRAS and BRAF mutations in primary colorectal tumors (PT) are predictive of nonresponse to anti–epidermal growth factor receptor (EGFR) antibodies in patients with metastatic colorectal cancer (mCRC). The question of primary resistance to anti-EGFR treatment as a result of the presence of KRAS or BRAF mutations only in metastases has been raised but not resolved.

Methods

We analyzed the mutational status of KRAS and BRAF in 64 new patients with mCRC and performed a systematic review of published data from 285 patients.

Results

A total of 285 and 95 matched PT/metastases were available for the analysis of the KRAS and the BRAF status, respectively. An identical mutational pattern of KRAS in PT and the matching metastases were reported in all the cases but 14 (5%). In six cases (2%), KRAS was mutated in the PT and wild type in the metastatic site, whereas in eight cases (3%), KRAS was wild type in the PT and mutated in the metastatic site. An identical mutational pattern of BRAF in PT and the matching metastases was reported in all but two cases (3%). In one case (1.5%), BRAF was mutated in the PT and wild type in the metastatic site, whereas in one case (1.5%), BRAF was wild type in the PT and mutated in the metastatic site.

Conclusions

The acquisition by metastases of a KRAS or a BRAF mutation that was not present in the PT is a rare event, occurring in 5% of cases of mCRC. This is not a frequent mechanism of primary resistance to anti-EGFR treatments in mCRC.

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Acknowledgment

We thank Delphine Le Corre and Pierre Laurent-Puig (INSERM UMR-S775, Centre universitaire des Saints Pères, Paris, France) for their helpful advice and Nathalie Leroudier (Institut de Pharmacologie Moléculaire et Cellulaire, Sophia-Antipolis, France) for the sequencing analyses. This work was supported by the Comité des Alpes-Maritimes de la Ligue Nationale Contre le Cancer, the University Hospital Centre of Nice (Contrat d’Incitation à la Recherche 2006), and the Institut National du Cancer.

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Authors and Affiliations

  1. Laboratory of Solid Tumors Genetics, Nice University Hospital, Nice, France

    Antoine Italiano MD, PhD, Thibault Fabas MSc & Florence Pedeutour PharmD, PhD

  2. Faculty of Medicine, CNRS, UMR 6543, Nice, France

    Antoine Italiano MD, PhD, Thibault Fabas MSc & Florence Pedeutour PharmD, PhD

  3. Department of Medical Oncology, Institut Bergonie, Bordeaux, France

    Antoine Italiano MD, PhD, Yves Becouarn MD, René Brunet MD & Marianne Fonck MD

  4. Department of Pathology, Institut Bergonie, Bordeaux, France

    Isabelle Hostein PhD & Isabelle Soubeyran MD, PhD

  5. General Surgery and Surgical Oncology Department, Nice University Hospital, Nice, France

    Daniel Benchimol MD

  6. Department of Surgery, Institut Bergonie, Bordeaux, France

    Serge Evrard MD

  7. Gastrointestinal Surgery Department, Liver Transplant Unit, Nice University Hospital, Nice, France

    Jean Gugenheim MD

  8. Department of Medical Oncology, Centre Antoine-Lacassagne, Nice, France

    Eric François MD

  9. Department of Pathology, Nice University Hospital, Nice, France

    Marie-Christine Saint-Paul MD

Authors
  1. Antoine Italiano MD, PhD
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  2. Isabelle Hostein PhD
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  3. Isabelle Soubeyran MD, PhD
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  4. Thibault Fabas MSc
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  5. Daniel Benchimol MD
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  6. Serge Evrard MD
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  7. Jean Gugenheim MD
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  10. Marianne Fonck MD
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  12. Marie-Christine Saint-Paul MD
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  13. Florence Pedeutour PharmD, PhD
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Correspondence to Antoine Italiano MD, PhD.

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Italiano, A., Hostein, I., Soubeyran, I. et al. KRAS and BRAF Mutational Status in Primary Colorectal Tumors and Related Metastatic Sites: Biological and Clinical Implications. Ann Surg Oncol 17, 1429–1434 (2010). https://doi.org/10.1245/s10434-009-0864-z

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  • DOI: https://doi.org/10.1245/s10434-009-0864-z

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