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.