title: BRAFV600E mutation analysis by immunohistochemistry in patients with thoracic metastases from colorectal cancer.
abstract: The BRAF(V600E) 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 BRAF(V600E) in the thoracic metastases of sporadic mCRC patients has not been evaluated until now. The purpose of this study was to compare BRAF(V600E) IHC staining with molecular biology methods and to define the diagnostic value of the VE1 antibody for the detection of BRAF(V600E) 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 BRAF(V600E) 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 BRAF(V600E) in 34 of 310 (11%) cases or a non-BRAF(V600E) mutation in 5 of 310 (2%) cases. IHC with VE1 was strongly positive in 32 of 34 (88%) BRAF(V600E) mutated tumours and negative in non-BRAF(V600E) mutated tumours. IHC using the VE1 clone is a specific and sensitive method for the detection of BRAF(V600E) and may be either a complementary or an alternative method to molecular testing in mCRC patients.
authors.affiliation: 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.
authors.forename: Marius I
authors.initials: MI
authors.lastname: Ilie
authors.forename: Elodie
authors.initials: E
authors.lastname: Long-Mira
authors.forename: Véronique
authors.initials: V
authors.lastname: Hofman
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mouroux
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Vignaud
authors.forename: Guillaume
authors.initials: G
authors.lastname: Gauchotte
authors.forename: Hugues
authors.initials: H
authors.lastname: Begueret
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Merlio
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.forename: Xavier
authors.initials: X
authors.lastname: Hébuterne
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology*; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012680:Sensitivity and Specificity; D013899:Thoracic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf