Melanoma IHC Test Useful for Detecting BRAF V600E Mutations

When it comes to cutaneous malignant melanoma (CMM), BRAF V600E is a common mutation found in approximately 50% of cases. Currently, BRAF mutations are detected by using DNA tests, but there may be an alternative assay that's less expensive, requires less tissue, more efficient, and thought to be more sensitive.

Using the VE1 antibody, the objective of this study-which was published in the January 2015 issue of JAMA Dermatology-was to test the use of VE1 immunohistochemical (IHC) analysis on CMM to better assess BRAFV600E expression, and to also determine intratumoral and intertumoral heterogeneity.  

Researchers conducted a retrospective cohort study at Karolinska University Hospital from September 2012 to September 2013, examining CMM cases (124 primary tumors and 76 metastases) with VE1 IHC analysis, and results were compared with DNA mutation analyses.

Positive staining results with the VE1 antibody were detected in 94 of 200 tumors (47.0%). However, VE1 staining intensity varied among the primary tumors and corresponding metastases in 63 of 135 tumors (46.7%), but a change of mutational status based on DNA analysis was found in only four matched tumors (3.0%). Dissimilar findings between DNA mutation analysis and IHC analysis were observed in 12 tumors. The overall sensitivity and specificity of VE1 IHC analysis were 96.7% and 94.5%, respectively. A comparable sensitivity was obtained for primary and metastatic CMMs. The specificity was lower among primary CMM (92.4%) compared with metastases (98.0%).

Based on study results, VE1 IHC analysis was found to be a helpful and rapid method to detect BRAF V600E mutations--which may also contribute to the detection of intratumoral and intertumoral heterogenetic subclones.  For those tumors exhibiting positive results, BRAF-mutation testing should be conducted to confirm, and for those tumors with a negative test result, further analysis is recommended.

In summary, the use of BRAF V600E mutation–specific monoclonal antibody VE1 IHC analysis may facilitate rapid detection of BRAF V600E mutations in CMM and demonstrate heterogeneity among tumors.