Expression of BRAF V600E mutant protein in epithelial ovarian tumors. 2013

Matthias Preusser, and David Capper, and Anna S Berghoff, and Reinhard Horvat, and Fritz Wrba, and Monika Schindl, and Sebastian F Schoppmann, and Andreas von Deimling, and Peter Birner
Department of Medicine I, Medical University of Vienna, Vienna, Austria.

BACKGROUND Genetic analyses have identified BRAF V600E mutations in a subset of ovarian carcinomas. The aim of this study was to investigate the expression of BRAF V600E aberrant protein using a novel mutation-specific antibody in epithelial ovarian tumors. METHODS We immunohistochemically analyzed expression of V600E-mutant BRAF protein in archival formalin-fixed, paraffin-embedded tissue specimens of 142 epithelial ovarian tumors [98 invasive carcinomas and 44 tumors of low malignant potential (LMP)] using monoclonal antibody VE1. BRAF mutation status was validated in all immunopositive cases and in 6 immunonegative control cases by gene sequencing. RESULTS We found anti-BRAF V600E immunolabeling in 4 serous carcinomas and 5 serous LMP. Presence of a BRAF V600E mutation was confirmed by sequencing analysis in 6 of the 9 cases (3 LMP tumors, 3 low-grade carcinomas). In 2 partially VE1-positive tumors deriving from 1 patient (1 LMP and 1 contralateral invasive high-grade serous carcinoma), genetic analysis repeatedly resulted in BRAF wild-type, arguing for false-positive immunostaining results. One immunopositive case was repeatedly inconclusive in genetic analysis. In all 6 genetically confirmed cases, BRAF V600E mutant protein expression was homogenous throughout the tumor tissue. CONCLUSIONS We found BRAF V600E mutations in 13% (4/31) of serous LMP and 5% (3/62) of invasive serous carcinomas. No BRAF V600E mutations were detected in nonserous epithelial ovarian tumors. For reliable assessment of the BRAF V600E status in ovarian epithelial tumor samples, an integrated approach using immunohistochemistry and genetic analysis seems advisable, as both methods lead to incorrect results in some cases.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009361 Neoplasm Invasiveness Ability of neoplasms to infiltrate and actively destroy surrounding tissue. Invasiveness, Neoplasm,Neoplasm Invasion,Invasion, Neoplasm
D009375 Neoplasms, Glandular and Epithelial Neoplasms composed of glandular tissue, an aggregation of epithelial cells that elaborate secretions, and of any type of epithelium itself. The concept does not refer to neoplasms located in the various glands or in epithelial tissue. Epithelial Cell Neoplasms,Glandular Cell Neoplasms,Epithelial Neoplasms,Glandular Neoplasms,Glandular and Epithelial Neoplasms,Neoplasms, Epithelial,Neoplasms, Glandular,Neoplasms, Glandular Epithelial,Cell Neoplasm, Epithelial,Cell Neoplasm, Glandular,Cell Neoplasms, Epithelial,Epithelial Cell Neoplasm,Epithelial Neoplasm,Epithelial Neoplasm, Glandular,Glandular Cell Neoplasm,Glandular Epithelial Neoplasm,Glandular Epithelial Neoplasms,Glandular Neoplasm,Neoplasm, Epithelial,Neoplasm, Epithelial Cell,Neoplasm, Glandular,Neoplasm, Glandular Cell,Neoplasm, Glandular Epithelial
D010051 Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. Cancer of Ovary,Ovarian Cancer,Cancer of the Ovary,Neoplasms, Ovarian,Ovary Cancer,Ovary Neoplasms,Cancer, Ovarian,Cancer, Ovary,Cancers, Ovarian,Cancers, Ovary,Neoplasm, Ovarian,Neoplasm, Ovary,Neoplasms, Ovary,Ovarian Cancers,Ovarian Neoplasm,Ovary Cancers,Ovary Neoplasm
D002277 Carcinoma A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for "cancer." Carcinoma, Anaplastic,Carcinoma, Spindle-Cell,Carcinoma, Undifferentiated,Carcinomatosis,Epithelial Neoplasms, Malignant,Epithelioma,Epithelial Tumors, Malignant,Malignant Epithelial Neoplasms,Neoplasms, Malignant Epithelial,Anaplastic Carcinoma,Anaplastic Carcinomas,Carcinoma, Spindle Cell,Carcinomas,Carcinomatoses,Epithelial Neoplasm, Malignant,Epithelial Tumor, Malignant,Epitheliomas,Malignant Epithelial Neoplasm,Malignant Epithelial Tumor,Malignant Epithelial Tumors,Neoplasm, Malignant Epithelial,Spindle-Cell Carcinoma,Spindle-Cell Carcinomas,Tumor, Malignant Epithelial,Undifferentiated Carcinoma,Undifferentiated Carcinomas
D005189 False Positive Reactions Positive test results in subjects who do not possess the attribute for which the test is conducted. The labeling of healthy persons as diseased when screening in the detection of disease. (Last, A Dictionary of Epidemiology, 2d ed) False Positive Reaction,Positive Reaction, False,Positive Reactions, False,Reaction, False Positive,Reactions, False Positive
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012189 Retrospective Studies Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. Retrospective Study,Studies, Retrospective,Study, Retrospective
D015870 Gene Expression The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION. Expression, Gene,Expressions, Gene,Gene Expressions

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