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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 5/2010

01-05-2010 | Translational Research and Biomarkers

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

Authors: Antoine Italiano, MD, PhD, Isabelle Hostein, PhD, Isabelle Soubeyran, MD, PhD, Thibault Fabas, MSc, Daniel Benchimol, MD, Serge Evrard, MD, Jean Gugenheim, MD, Yves Becouarn, MD, René Brunet, MD, Marianne Fonck, MD, Eric François, MD, Marie-Christine Saint-Paul, MD, Florence Pedeutour, PharmD, PhD

Published in: Annals of Surgical Oncology | Issue 5/2010

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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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Metadata
Title
KRAS and BRAF Mutational Status in Primary Colorectal Tumors and Related Metastatic Sites: Biological and Clinical Implications
Authors
Antoine Italiano, MD, PhD
Isabelle Hostein, PhD
Isabelle Soubeyran, MD, PhD
Thibault Fabas, MSc
Daniel Benchimol, MD
Serge Evrard, MD
Jean Gugenheim, MD
Yves Becouarn, MD
René Brunet, MD
Marianne Fonck, MD
Eric François, MD
Marie-Christine Saint-Paul, MD
Florence Pedeutour, PharmD, PhD
Publication date
01-05-2010
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 5/2010
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-009-0864-z

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