BRAF(V600E) mutations and immunohistochemical expression of VE1 protein in low-grade serous neoplasms of the ovary Journal Article


Authors: Turashvili, G.; Grisham, R. N.; Chiang, S.; DeLair, D. F.; Park, K. J.; Soslow, R. A.; Murali, R.
Article Title: BRAF(V600E) mutations and immunohistochemical expression of VE1 protein in low-grade serous neoplasms of the ovary
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 BRAFV 600E (26, 34%), KRASG 12D (eight, 11%), and KRASG 12V (eight, 11%). BRAFV 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 BRAFV 600E-mutated tumours and correlated with BRAF mutation-associated histological features (P < 0.0001). Conclusions: BRAFV 600E mutations are significantly more common in SBTs than in LGSCs. Immunohistochemical expression of VE1 protein is associated strongly with BRAFV 600E mutation and BRAF mutation-associated histological features. VE1 immunohistochemistry is a reliable method for the detection of BRAFV 600E mutations. © 2018 John Wiley & Sons Ltd
Keywords: ovary; low-grade serous carcinoma; serous borderline tumour; ve1 immunohistochemistry; brafv 600e mutation
Journal Title: Histopathology
Volume: 73
Issue: 3
ISSN: 0309-0167
Publisher: Wiley Blackwell  
Date Published: 2018-09-01
Start Page: 438
End Page: 443
Language: English
DOI: 10.1111/his.13651
PROVIDER: scopus
PMCID: PMC6105553
PUBMED: 29770477
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
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MSK Authors
  1. Kay Jung Park
    305 Park
  2. Rachel Nicole Grisham
    169 Grisham
  3. Robert Soslow
    793 Soslow
  4. Rajmohan Murali
    219 Murali
  5. Deborah F DeLair
    106 DeLair
  6. Sarah   Chiang
    146 Chiang