The prognostic significance of the BRAFV600E mutation in papillary thyroid carcinoma detected by mutation-specific immunohistochemistry

McKelvie, Penelope; Chan, Fiona Y.; Yu, Yong; Waring, Paul; Gresshoff, Irma; Farrell, Stephen; Williams, Richard A.

doi:10.1097/pat.0000000000000008

Cited by 34 publications

(27 citation statements)

References 48 publications

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“…Our findings show that in colorectal carcinoma, VE1 IHC is not a reliable method for determining the BRAF V600E mutational status. In contrast, our results in melanoma and papillary thyroid carcinoma are in keeping with previously published data showing excellent concordance between molecular analysis and VE1 IHC (36)(37)(38)(39)(40)(41).…”

Section: Discussioncontrasting

confidence: 54%

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: Discussioncontrasting

confidence: 54%

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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“…Recently, a few studies have also investigated the prognostic value of BRAF protein expression and V600E mutation in PTC tumors using immunohistochemistry (Kondo et al, 2007;Capper et al, 2011;Feng et al, 2011;Koperek et al, 2012;McKelvie et al, 2013). In one of these (Feng et al, 2011), it was demonstrated that BRAF expression in PTC was significantly higher in tumors than in benign thyroid lesions.…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that this BRAF antibody might facilitate the use of BRAF molecular analysis for diagnosis, particularly in patients with uncertain diagnosis or with insufficient material for molecular analyses, or even as a surrogate for genetic testing in clinical decisions (Capper et al, 2011;Koperek et al, 2012). The VE1 antibody demonstrates high sensitivity in paraffin sections and may represent the new gold standard for the detection of the BRAF V600E mutation in PTC (Bullock et al, 2012;McKelvie et al, 2013;Routhier et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Several recent studies have established the important association of the BRAF V600E mutation in PTC prognosis (Xing et al, 2005;Lupi et al, 2007;Basolo et al, 2010;O'Neill et al, 2010;Capper et al, 2011;McKelvie et al, 2013). The V600E mutation results in a constitutively activated BRAF protein with a gain of function, independent of activator signals, and leading to continuous activation of the MAPK pathway, which may in turn result in the development of thyroid malignancies (Davies et al, 2002;Tang and Lee, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…A specific monoclonal antibody (VE1 clone) targeting the mutated form of the BRAF protein (V600E BRAF) has been used in several recent studies (Capper et al, 2011;Koperek et al, 2012;McKelvie et al, 2013) in order to distinguish the expression of the wild-type and the mutated BRAF proteins. It is possible that this BRAF antibody might facilitate the use of BRAF molecular analysis for diagnosis, particularly in patients with uncertain diagnosis or with insufficient material for molecular analyses, or even as a surrogate for genetic testing in clinical decisions (Capper et al, 2011;Koperek et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

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BRAF overexpression is associated with BRAF V600E mutation in papillary thyroid carcinomas

Silva¹,

Paula²,

Leal³

et al. 2015

Genet. Mol. Res.

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ABSTRACT.A common mutation in the BRAF gene, comprising the T1799A nucleotide transversion, which leads to the V600E amino acid substitution in the BRAF protein, has been observed in about 50% of papillary thyroid carcinomas (PTCs). However, BRAF protein expression has been rarely examined in such tumors. Clinical studies have shown important associations between BRAF mutation and clinical parameters in PTC, such as progression, invasion, and recurrence. The aim of this study was to evaluate the association between BRAF protein overexpression and the BRAF V600E mutation in a group of PTC patients. The study group included 116 patients with PTC from Araújo Jorge Hospital, Goiânia, Goiás, Brazil. Immunohistochemistry was utilized to analyze BRAF protein expression. Presence of the BRAF V600E mutation was determined by polymerase chain reaction amplification and restriction fragment length polymorphism, and confirmed by direct sequencing. The chi-square test with Yates correction and the Fisher exact test were used for statistical analysis. BRAF overexpression was detected in 55 patients with PTC (47.4%) and the BRAF V600E mutation was observed in 74 patients (63.8%). In the studied group, significant associations were observed between the BRAF V600E mutation and BRAF protein overexpression (P = 0.0115), and also between BRAF overexpression and extra-thyroid extension of the tumor (P = 0.0111). This study demonstrated a significant association between BRAF overexpression and the BRAF V600E mutation in PTC, highlighting the importance of these molecular events in the process of PTC carcinogenesis.

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Use of BRAF v600e immunocytochemistry on FNA direct smears of papillary thyroid carcinoma

Wobker

Kim

Hackman

et al. 2015

Cancer Cytopathology

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BACKGROUND: Mutations of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) are identified in almost half of all papillary thyroid carcinomas (PTCs). These mutations are specific for PTC and may confer a worse prognosis. An immunohistochemical (IHC) stain for BRAF is commercially available and has been validated in surgical specimens. Fine-needle aspiration (FNA) is frequently used as a diagnostic tool for risk stratification of thyroid nodules. Therefore, the authors evaluated the performance of immunostaining with the anti-BRAF antibody VE1 on FNA direct smears. METHODS: The authors identified 51 FNA specimens that had subsequent surgical resection specimens with a diagnosis of PTC. BRAF VE1 IHC was performed on the surgical specimens to determine their mutation status. The corresponding direct smears were then stained using the same VE1 stain to assess correlation. RESULTS: Twenty-two of the 46 included surgical specimens were positive for BRAF mutations (47.8%) by IHC, consistent with the published rates. The paired cytologic smears from these cases revealed 65.3% concordance. The overall sensitivity of BRAF staining on cytologic smears was 63.6%, and the specificity was 58.3%. Concordance rates were highest in specimens that were diagnosed as malignant or suspicious for malignancy (75% and 85.7%, respectively). The negative predictive value increased to 77.8% when suspicious for follicular neoplasm/suspicious cases were combined. CONCLUSIONS: Specimens that were malignant or suspicious on FNA were most likely to be BRAF concordant. Limitations to the interpretation of smears included low cellularity and obscuring blood, macrophages, or colloid. With further refinement, it is possible that BRAF immunocytochemistry can be applied prospectively to thyroid FNAs for risk stratification and to reduce false-negative rates. Cancer (Cancer Cytopathol) 2015;123:531-9.

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The prognostic significance of the BRAFV600E mutation in papillary thyroid carcinoma detected by mutation-specific immunohistochemistry

Cited by 34 publications

References 48 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

BRAF overexpression is associated with BRAF V600E mutation in papillary thyroid carcinomas

Use of BRAF v600e immunocytochemistry on FNA direct smears of papillary thyroid carcinoma

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