BRAFV600E mutations and immunohistochemical expression of VE1 protein in low‐grade serous neoplasms of the ovary. Issue 3 (22nd June 2018)

• Record Type: Journal Article
• Authors: Turashvili, Gulisa; Grisham, Rachel N; Chiang, Sarah; DeLair, Deborah F; Park, Kay J; Soslow, Robert A; Murali, Rajmohan
• Is Part Of: Histopathology. Volume 73:Issue 3(2018)
• Page Start: 438
• Page End: 443
• Publication Date: 2018-06-22
• Subjects: BRAFV600E mutation -- low‐grade serous carcinoma -- ovary -- serous borderline tumour -- VE1 immunohistochemistry; Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.13651
• Languages: English
• ISSNs: 0309-0167

Abstract

Abstract : 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 V 600E (26, 34%), KRAS G 12D (eight, 11%), and KRAS G 12V (eight, 11%). BRAF V 600E 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 V 600E ‐mutated tumours and correlated with BRAF mutation‐associated histological features ( P < 0.0001). Conclusions: BRAF V 600E mutations are significantly more common in SBTs than in LGSCs. Immunohistochemical expression of VE1 protein is associated strongly with BRAF V 600E mutation and BRAF mutation‐associated histological features. VE1 immunohistochemistry is a reliable method for the detection of BRAF V 600E mutations.