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BRAFV600E mutation analysis by immunohistochemistry in patients with thoracic metastases from colorectal cancer

Ilie, Marius I.1,2,3,4; Long-Mira, Elodie1,3; Hofman, Véronique1,2,3,4; Mouroux, Jérôme1,5; Vignaud, Jean-Michel6; Gauchotte, Guillaume6; Begueret, Hugues7; Merlio, Jean-Philippe7; Emile, Jean-François8,9; Hébuterne, Xavier1,10; Hofman, Paul1,2,3,4

doi: 10.1097/PAT.0000000000000113
Anatomical Pathology

Summary: The BRAFV600E mutation confers worse prognosis to metastatic colorectal cancer (mCRC) patients. In addition, this mutation has a negative predictive value for response to treatment with monoclonal antibodies against EGFR in patients with KRAS wild-type (wt) mCRC. The utility of immunohistochemistry (IHC) as an alternative approach for detection of BRAFV600E in the thoracic metastases of sporadic mCRC patients has not been evaluated until now. The purpose of this study was to compare BRAFV600E IHC staining with molecular biology methods and to define the diagnostic value of the VE1 antibody for the detection of BRAFV600E in this population.

BRAF mutations were analysed by two DNA sequencing methods (pyrosequencing and Sanger sequencing) in a Caucasian population of 310 sporadic mCRC with thoracic metastases patients expressing KRAS wt. Detection of the BRAFV600E mutation was performed in the corresponding tumours by IHC using the VE1 antibody and compared to results of the DNA-based assays.

Thirty-nine out of 310 (13%) of tumours harboured a BRAF mutation, which corresponded to either a BRAFV600E in 34 of 310 (11%) cases or a non-BRAFV600E mutation in 5 of 310 (2%) cases. IHC with VE1 was strongly positive in 32 of 34 (88%) BRAFV600E mutated tumours and negative in non-BRAFV600E mutated tumours.

IHC using the VE1 clone is a specific and sensitive method for the detection of BRAFV600E and may be either a complementary or an alternative method to molecular testing in mCRC patients.

1INSERM U1081/CNRS UMR7284, Team 3, University of Nice Sophia Antipolis, Antoine Lacassagne Cancer Center, Institute for Research on Cancer and Aging in Nice (IRCAN), Nice

2Human Biobank, Pasteur Hospital, Nice

3Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice

4Cancer Research Association (ARC) Labelled Team, Villejuif

5Department of Thoracic Surgery, Pasteur Hospital, Nice

6Laboratory of Pathology, University Hospital of Nancy-Brabois, Nancy

7Laboratory of Pathology, Haut Lévêque Hospital, Bordeaux

8Department of Pathology, Ambroise Paré Hospital, Paris

9EA 4340, Université de Versailles SQY, Boulogne

10Department of Gastroenterology, Archet Hospital, Nice, France

Address for correspondence: Professor P. Hofman, Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, 30 Voie Romaine, 06001 Nice Cedex 01, France. E-mail:

Received 12 October, 2013

Revised 3 December, 2013

Accepted 12 December, 2013

© 2014 Royal College of Pathologists of Australasia
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