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BRAF V 600E mutations and immunohistochemical expression of VE 1 protein in low‐grade serous neoplasms of the ovary
Author(s) -
Turashvili Gulisa,
Grisham Rachel N,
Chiang Sarah,
DeLair Deborah F,
Park Kay J,
Soslow Robert A,
Murali Rajmohan
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13651
Subject(s) - immunohistochemistry , protein expression , microbiology and biotechnology , serous fluid , cancer research , pathology , biology , medicine , gene , genetics
Aims The most common BRAF mutation in ovarian low‐grade serous neoplasms ( LGSN s) involves substitution of valine by glutamic acid at position 600 (V600E). Small studies have demonstrated high specificity of immunohistochemistry with mutation‐specific monoclonal antibody VE 1. We sought to investigate the expression of VE 1 protein in LGSN s 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 ( SBT s) and low‐grade serous carcinomas ( LGSC s) diagnosed between 2000 and 2012. VE 1 immunohistochemistry was performed on formalin‐fixed, paraffin‐embedded tissue sections. Tumours with ≥50% positive cells were considered positive. Of 121 LGSN s, there were 73 SBT s, eight SBT s with micropapillary features (mp SBT ) and 40 LGSC s (22 primary, 18 metastatic). VE 1 was positive in 52% (38 of 73) of SBT s and 9% (two of 22) of primary LGSC s, and in none of the mp SBT s and metastatic LGSC s ( 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 SBT s and 5% (one of 22) of LGSC s ( P < 0.0001). VE 1 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 SBT s than in LGSC s. Immunohistochemical expression of VE 1 protein is associated strongly with BRAF V 600E mutation and BRAF mutation‐associated histological features. VE 1 immunohistochemistry is a reliable method for the detection of BRAF V 600E mutations.