VE1 immunohistochemistry in pituitary adenomas is not associated with BRAF V600E mutation

Sperveslage, Jan; Gierke, Midea; Capper, David; Honegger, Jürgen; Sipos, Bence; Beschorner, Rudi; Schittenhelm, Jens

doi:10.1007/s00401-013-1118-5

Cited by 21 publications

(20 citation statements)

References 10 publications

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“…Although other studies reported excellent concordance between molecular analysis and VE1 IHC in some central nervous system tumors, specifically epithelioid glioblastomas (43), pleomorphic xanthoastrocytoma (44), and dysembryoplastic neuroepithelial tumor (45), other authors found that the utility of VE1 IHC is limited in pituitary adenomas (46), similar to what we found in colorectal carcinoma. Sperveslage and colleagues evaluated 78 pituitary adenomas using two different platforms (Leica Bond-Max and Ventana OptiView).…”

Section: Discussionsupporting

confidence: 86%

Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing

Estrella

Tetzlaff

Bassett

et al. 2015

Molecular Cancer Therapeutics

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Although sequencing provides the gold standard for identifying colorectal carcinoma with BRAF V600E mutation, immunohistochemistry (IHC) with the recently developed mouse monoclonal antibody VE1 for BRAF V600E protein has shown promise as a more widely available and rapid method. However, we identified anecdotal discordance between VE1 IHC and sequencing results and therefore analyzed VE1 staining by two different IHC methods (Leica Bond and Ventana BenchMark) in whole tissue sections from 480 colorectal carcinomas (323 BRAF wild-type, 142 BRAF V600E mutation, and 15 BRAF non-V600E mutation). We also compared the results with melanomas and papillary thyroid carcinomas (PTC). With the Bond method, among 142 BRAF V600E-mutated colorectal carcinomas, 77 (54%) had diffuse VE1 staining and 48 (33%) had heterogeneous staining, but 17 (12%) were negative. Among 323 BRAF wild-type colorectal carcinomas, 196 (61%) were negative, but 127 (39%) had staining, including 7 with diffuse staining. When positivity was defined as staining in !20% of tumor cells, VE1 IHC had sensitivity of 75% and specificity of 93% for BRAF V600E mutation. With the Ventana method, among 57 BRAF V600E-mutated colorectal carcinomas, 36 (63%) had diffuse VE1 staining, whereas 6 (11%) had no or weak (<20% of tumor cells) staining. Among 33 BRAF wildtype colorectal carcinomas, 16 (48%) had no or weak staining, whereas 15 (45%) had heterogeneous staining. In contrast with colorectal carcinoma, Bond and Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing results. We conclude that VE1 IHC produces suboptimal results in colorectal carcinoma and should not be used to guide patient management.

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Section: Discussionsupporting

confidence: 86%

Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing

Estrella

Tetzlaff

Bassett

et al. 2015

Molecular Cancer Therapeutics

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“…Genotyping for BRAF mutations, including V600E, were negative in all cases. Our findings are consistent with those of Sperveslage et al, 15 who found that the VE1 antibody stained 21% of pituitary adenomas in the absence of the BRAF V600E mutation. In their study, the case with the strongest VE1 staining was an ACTH-expressing adenoma, and they also observed staining in growth hormone-producing and mammosomatotroph adenomas.…”

Section: Discussionsupporting

confidence: 83%

VE1 Antibody Immunoreactivity in Normal Anterior Pituitary and Adrenal Cortex Without Detectable BRAF V600E Mutations

Mordes

Lynch

Campbell

et al. 2014

American Journal of Clinical Pathology

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The BRAF gene is found to be mutated in various hematologic as well as solid tumors, including hairy cell leukemia, 1 pleomorphic xanthoastrocytoma, 2,3 malignant melanoma, 4 papillary thyroid carcinomas, 5 gastrointestinal carcinomas, 6,7 and lung adenocarcinomas. 8 The mutantspecific BRAF V600E (clone VE1) antibody was developed to recognize the most common activating mutation in BRAF using immunohistochemistry on formalin-fixed paraffinembedded tissue, and was initially validated in melanoma and papillary thyroid carcinoma. 9 This antibody was also shown to detect BRAF V600E mutations in colon carcinoma, lung carcinoma, and brain metastases, including metastatic melanoma. 2,[10][11][12][13] We report that the VE1 antibody stains normal anterior pituitary gland and adrenal cortex without detectable BRAF V600E mutations.Upon completion of this activity you will be able to:• describe the distribution of reactivity to VE1 monoclonal antibody in endocrine tissues.• correlate the VE1 monoclonal antibody staining of endocrine organs with BRAF V600E mutation.• outline the role of concordant genetic testing when using VE1 monoclonal antibody as a screening tool for BRAF V600E mutation in tumors.The ASCP is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The ASCP designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit ™ per article. Physicians should claim only the credit commensurate with the extent of their participation in the activity. This activity qualifies as an American Board of Pathology Maintenance of Certification Part II Self-Assessment Module.The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.Questions appear on p 896. Exam is located at www.ascp.org/ajcpcme.

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“…In contrast to the labor-intensive detection of BRAF V600E mutation by molecular testing, identification of BRAF V600E mutant protein by immunohistochemistry is a rapid method that may be quickly implemented in diagnostic pathology practice since it is a widespread technique available in most academic centers as well as in non-academic pathology practices. However, validation of the BRAF V600E mutation IHC specificity by comparative molecular analysis should be performed for each tumor entity before routine diagnostic implementation, since it has been recently reported that in pituitary adenomas, the BRAF V600E mutation-specific VE1 immunostaining is not associated with presence of BRAF V600E mutation [35]. …”

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry is highly sensitive and specific for detection of BRAF V600E mutation in pleomorphic xanthoastrocytoma

Ida

Vrana

Rodríguez

et al. 2013

acta neuropathol commun

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BackgroundHigh frequencies of the BRAF V600E mutation have been reported in pleomorphic xanthoastrocytoma (PXA). Recently, a BRAF V600E mutation-specific antibody has been developed and validated. We evaluated the immunohistochemical (IHC) detection of BRAF V600E mutation in PXA by comparing to gold standard molecular analysis and investigating the interobserver variability of the IHC scoring. We performed BRAF V600E IHC in 46 cases, of which 37 (80%) cases had sufficient tumor tissue for molecular analysis. IHC detection was performed using monoclonal mouse antibody VE1 (Spring Bioscience). IHC slides were scored independently by four reviewers blind to molecular data, including a primary (gold standard) and three additional reviewers. BRAF V600E mutation status was assessed by allele-specific polymerase chain reaction (PCR) with fragment analysis.ResultsAll 46 cases showed interpretable BRAF V600E IHC results: 27 (59%) were positive (strong cytoplasmic staining), 19 (41%) were negative (6 of these cases with focal/diffuse weak cytoplasmic staining, interpreted as nonspecific by the primary reviewer). By molecular analysis, all 37 cases that could be tested had evaluable results: 22 (59%) cases were positive for BRAF V600E mutation and were scored as “IHC-positive”, and 15 (41%) were negative (including 11 cases scored as “IHC-negative” and 4 cases scored as negative with minimal nonspecific staining). IHC detection of BRAF V600E mutant protein was congruent in all 37 cases that were successfully evaluated by molecular testing (sensitivity and specificity of 100%). Agreement for IHC scoring among the 4 reviewers was almost perfect (kappa 0.92) when cases were scored as “positive/negative” and substantial (kappa 0.78) when minimal nonspecific staining was taken into account.ConclusionsWe conclude that detection of BRAF V600E mutation by immunohistochemistry is highly sensitive and specific. BRAF V600E IHC interpretation is usually straightforward, but awareness of possible nonspecific staining is necessary and training is recommended. It is a practical rapid method that may avoid the need of labor-intensive molecular testing and may be most valuable in small biopsies unsuitable for molecular analysis.

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VE1 immunohistochemistry in pituitary adenomas is not associated with BRAF V600E mutation

Cited by 21 publications

References 10 publications

Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing

Assessment of BRAF V600E Status in Colorectal Carcinoma: Tissue-Specific Discordances between Immunohistochemistry and Sequencing

VE1 Antibody Immunoreactivity in Normal Anterior Pituitary and Adrenal Cortex Without Detectable BRAF V600E Mutations

Immunohistochemistry is highly sensitive and specific for detection of BRAF V600E mutation in pleomorphic xanthoastrocytoma

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