Immunohistochemistry versus next-generation sequencing for the routine detection of BRAF V600E mutation in melanomas

Just, Pierre‐Alexandre; Audebourg, Anne; Pasmant, Éric; Clauser, Éric; Carlotti, A.; Laurent, Sara; Avril, Marie-Françoise; Vacher-Lavenu, Marie-Cécile; Vidaud, Michel; Terris, Benoı̂t

doi:10.1016/j.humpath.2014.05.017

Cited by 9 publications

(7 citation statements)

References 2 publications

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“…Our study is the largest reported comparison of BRAF IHC and genomic testing from the UK and reflects the performance of these tests in day-to-day clinical practice at two cancer centres using assays that are currently available to all UK pathology departments either in-house or via national reference centres. Our results are closely comparable to previous validation studies ( Long et al , 2011 ; Colomba et al , 2013 ; Just et al , 2014 ; Pearlstein et al , 2014 ; Thiel et al , 2015 ).…”

Section: Discussionsupporting

confidence: 92%

“…Moreover, ascertaining BRAF status in metastatic melanoma facilitates patients' entry into clinical trials with BRAF inhibitors. There are several methods to detect BRAF mutations including immunohistochemistry (IHC), pyrosequencing, Sanger sequencing and real-time PCR ( Colomba et al , 2013 ; Long et al , 2013 ; Just et al , 2014 ; Thiel et al , 2015 ). Table 1 highlights the abilities of these techniques to detect the various mutations.…”

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confidence: 99%

“…The drawback is that it is relatively time-consuming and has a limited capacity. The VE1 antibody clone has been validated and shown to detect the V600E and the rarer V600E2-mutated variants with a sensitivity and specificity of 95–100% and 97–100%, respectively, ( Long et al , 2011 ; Colomba et al , 2013 ; Just et al , 2014 ; Pearlstein et al , 2014 ; Thiel et al , 2015 ), although data from UK-based centres were lacking. IHC may be preferable for routine clinical use since it is quicker, cheaper and can be offered by more histopathology laboratories.…”

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confidence: 99%

“…IHC may be preferable for routine clinical use since it is quicker, cheaper and can be offered by more histopathology laboratories. However, since the antibody does not identify the less common V600K, V600R and non-V600 mutations, the overall sensitivity of IHC to detect BRAF mutations when compared with genomic methods is reported to be 76–89% ( Long et al , 2011 ; Just et al , 2014 ; Thiel et al , 2015 ).…”

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confidence: 99%

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A UK feasibility and validation study of the VE1 monoclonal antibody immunohistochemistry stain for BRAF-V600E mutations in metastatic melanoma

Paterson

Maraka

et al. 2016

Br J Cancer

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Background:Determining the BRAF mutation status of patients with advanced metastatic melanoma is essential in order to assess patients' eligibility for targeted BRAF inhibitor therapy. The aim of this study was to validate the utility of immunohistochemistry (IHC) to rapidly obtain the BRAF status in the UK cancer centre setting.Methods:All samples sent for molecular testing for detection of the BRAF mutation over a 26-month period were prospectively tested using the VE1 monoclonal antibody IHC stain.Results:Two-hundred and nineteen samples from 214 patients were identified. All patients were AJCC stage III/IV, except one. There was an overall 95.0% (208/219) concordance rate, with a sensitivity of 94.4% (84/89) and a specificity of 95.4% (124/130) when using genomic assays as the gold standard. Discordance resulted from the inability of the molecular technique to detect the V600E2 mutation and an inability of the IHC staining technique to detect non-V600E mutations. Molecular testing on smaller tumour deposits was also unreliable.Conclusions:IHC staining has good sensitivity and excellent specificity for BRAF V600E mutations. BRAF IHC can be incorporated into a BRAF mutation testing algorithm for UK cancer centres to as a feasible first-line assay and identify a subset of cases that require subsequent genomic testing. It has the additional major advantages of reduced cost and rapid turnaround time.

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Section: Discussionsupporting

confidence: 92%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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A UK feasibility and validation study of the VE1 monoclonal antibody immunohistochemistry stain for BRAF-V600E mutations in metastatic melanoma

Paterson

Maraka

et al. 2016

Br J Cancer

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“…Recent studies have shown that IHC for BRAF V600E and NRAS Q16R has excellent specificity that is highly concordant with molecular testing (e.g. PCR, pyrosequencing or next-generation sequencing) [ 38 , 39 , 40 , 41 ]. Other point mutations of BRAF (V600K, V600Q, and V600R) or NRAS (Q61K, Q61L, Q61H) melanomas do not stain positively with BRAF VE1 and NRAS Q61R antibodies [ 39 , 41 ], respectively.…”

Section: Ihc Markers For Melanoma Diagnosismentioning

confidence: 99%

Diagnostic Immunohistochemistry in Cutaneous Neoplasia: An Update

2015

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Immunohistochemistry (IHC) is an important adjunct in the diagnosis of neoplastic skin diseases. In addition to the many established IHC markers currently in use, new markers continue to emerge, although their general acceptance and routine application requires robust validation. Here, we summarize the most well-established and commonly used biomarkers along with an array of newer ones reported in the past several decades that either demonstrate or hold high clinical promise in the field of cutaneous pathology. We also highlight recent applications of novel IHC markers in melanoma diagnosis including genetic mutation status markers [e.g. BRAF (v-raf murine sarcoma viral oncogene homolog B) and NRAS (neuroblastoma RAS viral oncogene homolog)] and an epigenetic alteration marker (e.g. 5-hydroxymethylcytosine). We specifically focus on the role of IHC in the differential diagnosis of cutaneous lesions that fall under the following categories: melanoma, epidermal tumors with an intraepidermal epitheliomatous pattern, spindle cell lesions of the dermis, small round blue cell tumors of the dermis, and cutaneous adnexal tumors. While IHC is a valuable tool in diagnostic dermatopathology, marker selection and interpretation must be highly informed by clinical context and the histologic differential diagnosis. With rapid progress in our understanding of the genetic and epigenetic mechanisms of tumorigenesis, new IHC markers will continue to emerge in the field of diagnostic dermatopathology.

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High specificity and sensitivity of NRAS Q61R immunohistochemistry (IHC) in melanomas

Just

Pouliquen

Audebourg

et al. 2016

Journal of the American Academy of Dermatology

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Immunohistochemistry versus next-generation sequencing for the routine detection of BRAF V600E mutation in melanomas

Cited by 9 publications

References 2 publications

A UK feasibility and validation study of the VE1 monoclonal antibody immunohistochemistry stain for BRAF-V600E mutations in metastatic melanoma

A UK feasibility and validation study of the VE1 monoclonal antibody immunohistochemistry stain for BRAF-V600E mutations in metastatic melanoma

Diagnostic Immunohistochemistry in Cutaneous Neoplasia: An Update

High specificity and sensitivity of NRAS Q61R immunohistochemistry (IHC) in melanomas

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