BRAF^V600E mutations and immunohistochemical expression of VE1 protein in low-grade serous neoplasms of the ovary

Aims: The most common BRAF mutation in ovarian low-grade serous neoplasms (LGSNs) involves substitution of valine by glutamic acid at position 600 (V600E). Small studies have demonstrated high specificity of immunohistochemistry with mutation-specific monoclonal antibody VE1. We sought to investigate the expression of VE1 protein in LGSNs and its correlation with BRAF mutation-associated histological features and BRAF mutation status.

Methods and results: We reviewed pathology reports and available slides from ovarian serous borderline tumours (SBTs) and low-grade serous carcinomas (LGSCs) diagnosed between 2000 and 2012. VE1 immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissue sections. Tumours with ≥50% positive cells were considered positive. Of 121 LGSNs, there were 73 SBTs, eight SBTs with micropapillary features (mpSBT) and 40 LGSCs (22 primary, 18 metastatic). VE1 was positive in 52% (38 of 73) of SBTs and 9% (two of 22) of primary LGSCs, and in none of the mpSBTs and metastatic LGSCs (P < 0.0001). Of 76 tumours with known mutation status, 42 (55%) harboured mutations, including BRAF^V600E (26, 34%), KRAS^G12D (eight, 11%), and KRAS^G12V (eight, 11%). BRAF^V600E mutations were present in 48% (25 of 52) of SBTs and 5% (one of 22) of LGSCs (P < 0.0001). VE1 was positive in 96% (25 of 26) of BRAF^V600E -mutated tumours and correlated with BRAF mutation-associated histological features (P < 0.0001).

Conclusions: BRAF^V600E mutations are significantly more common in SBTs than in LGSCs. Immunohistochemical expression of VE1 protein is associated strongly with BRAF^V600E mutation and BRAF mutation-associated histological features. VE1 immunohistochemistry is a reliable method for the detection of BRAF^V600E mutations.