Detection of the BRAF V600E mutation in serous ovarian tumors: a comparative analysis of immunohistochemistry with a mutation-specific monoclonal antibody and allele-specific PCR

Bösmüller, Hans; Fischer, Anna; Pham, Deborah Lan; Fehm, Tanja; Capper, David; Deimling, Andreas von; Bonzheim, Irina; Staebler, Annette; Fend, Falko

doi:10.1016/j.humpath.2012.07.010

Cited by 83 publications

(87 citation statements)

References 27 publications

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“…Several studies have shown that anti‐BRAF‐V600E IHC had a sensitivity and specificity over 95% in cutaneous melanoma (Capper et al., 2011; Colomba et al., 2013; Long et al., 2013; Ritterhouse & Barletta, 2015). In colon and thyroid cancers, IHC also proved consistent (Bösmüller et al., 2013; He, Zhao, Zhang, & Gong, 2014; Ritterhouse & Barletta, 2015), but its reliability remains to be assessed in large series of primary CNS tumors. We studied BRAF‐V600E expression in 140 glial and GNT.…”

Section: Discussionmentioning

confidence: 99%

BRAF‐V600E immunohistochemistry in a large series of glial and glial–neuronal tumors

et al. 2017

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IntroductionSome glial–neuronal tumors (GNT) (pleomorphic xantho‐astrocytoma [PXA], ganglioglioma [GG]) display BRAF‐V600E mutation, which represents a diagnostic clue to these entities. Targeted therapies against BRAF‐V600 protein have shown promising results in GNT. The aim of this study was to assess the utility of BRAF‐V600E immunohistochemistry (IHC, clone VE1) in daily practice in a series of 140 glial, and GNT compared to molecular biology (MB) techniques.MethodsWe performed BRAF‐V600E IHC on all 140 cases. We used Sanger sequencing and allele‐specific quantitative PCR (ASQ‐PCR) to detect BRAF‐V600E mutation when sufficient amount of materiel was available.Results BRAF‐V600E immunostaining was detected in 29.5% of cases (41/140 cases; 61.5% GG/GC/AGG (32/52), 33% PXA, 6.6% pilocytic astrocytomas). In 47 cases, MB could be performed: Sanger sequencing and ASQ‐PCR in 34 cases, ASQ‐PCR only in 11 cases, and Sanger sequencing only in two cases. In initial tumors, Sanger sequencing identified BRAF‐V600E mutation in 19.5% tumors (seven of 36 tested cases). ASQ‐PCR showed mutation in 48.5% tumors (17/35 tested cases). In six cases (5 GG, one PXA), the results were discordant between IHC and MB; the five GG cases were immunopositive for BRAF‐V600E but wild type with both MB techniques. In another 7 GG, the percentage of mutated (ganglion) cells was low, and Sanger sequencing failed to detect the mutation, which was detected by IHC and ASQ‐PCR.ConclusionsIn tumors with few mutated cells (e.g., GG), anti‐BRAF‐V600E IHC appears more sensitive than Sanger sequencing. The latter, although considered as the gold standard, is not to be used up‐front to detect BRAF mutation in GG. The combination of IHC and ASQ‐PCR appears more efficient to appraise the indication of targeted therapies in these glioneuronal tumors.

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Section: Discussionmentioning

confidence: 99%

BRAF‐V600E immunohistochemistry in a large series of glial and glial–neuronal tumors

et al. 2017

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“…As part of the genomic characterization of her LCH, immunohistochemistry for the BRAF V600E protein was performed on a skin biopsy sample and on the bone marrow as well, using a well-described and validated BRAF V600E-specific antibody (16)(17)(18). Within the bone marrow, the majority of the CD1a-negative macrophages were BRAF V600E positive by immunostain ( Figure 2, E and F).…”

Section: Knowledge Of Genomic Alterations Improves Clinical Outcomesmentioning

confidence: 99%

Real-time genomic profiling of histiocytoses identifies early-kinase domain BRAF alterations while improving treatment outcomes

et al. 2017

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“…40 A caveat to this is that one must take care in examining immunohistochemical specimens for BRAF status, as the VE1 antibody has been shown to react with certain BRAF WT tissues, such as normal cells in the anterior pituitary as well as ciliated epithelial cells. 4,25,28,37 Immunohistochemistry can also be used to diagnose craniopharyngioma based on CTNNB1 status. In PCP, b-catenin is localized to the cell membrane, whereas…”

Section: Diagnosticsmentioning

confidence: 99%

Diagnosis and management of craniopharyngiomas in the era of genomics and targeted therapy

Martínez-Gutiérrez

D’Andrea²,

Cahill

et al. 2016

FOC

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Craniopharyngiomas are rare intracranial neoplasms that pose clinical challenges due to their location adjacent to vital structures. The authors have previously shown high mutation rates of BRAF V600E in papillary craniopharyngioma and of CTNNB1 in adamantinomatous craniopharyngioma. These activating driver mutations are potential therapeutic targets, and the authors have recently reported a significant response to BRAF/MEK inhibition in a patient with multiply recurrent PCP. As these targetable mutations warrant prospective research, the authors will be conducting a national National Cancer Institute–sponsored multicenter clinical trial to investigate BRAF/MEK inhibition in the treatment of craniopharyngioma. In this new era of genomic discovery, the treatment paradigm of craniopharyngioma is likely to change.

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Detection of the BRAF V600E mutation in serous ovarian tumors: a comparative analysis of immunohistochemistry with a mutation-specific monoclonal antibody and allele-specific PCR

Cited by 83 publications

References 27 publications

BRAF‐V600E immunohistochemistry in a large series of glial and glial–neuronal tumors

BRAF‐V600E immunohistochemistry in a large series of glial and glial–neuronal tumors

Real-time genomic profiling of histiocytoses identifies early-kinase domain BRAF alterations while improving treatment outcomes

Diagnosis and management of craniopharyngiomas in the era of genomics and targeted therapy

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