BRAF(V600E) and NRAS(Q61L/Q61R) mutation analysis in metastatic melanoma using immunohistochemistry: a study of 754 cases highlighting potential pitfalls and guidelines for interpretation and reporting.
Histopathology
; 69(4): 680-6, 2016 Oct.
Article
en En
| MEDLINE
| ID: mdl-27151331
ABSTRACT
BACKGROUND AND AIMS:
BRAF or NRAS mutations occur in approximately 60% of cutaneous melanomas, and the identification of such mutations underpins the appropriate selection of patients who may benefit from BRAF and MEK inhibitor targeted therapies. The utility of immunohistochemistry (IHC) to detect NRAS(Q61L) mutations is currently unknown. This study sought to assess the sensitivity and specificity of anti-BRAF(V600E) (VE1), anti-NRAS(Q61R) (SP174) and anti-NRAS(Q61L) (26193) antibodies for mutation detection in a large series of cases. METHODS ANDRESULTS:
Mutation status was determined using the OncoCarta assay in 754 cutaneous melanomas. IHC with the anti-BRAF(V600E) antibody was performed in all cases, and the anti-NRAS(Q61R) and anti-NRAS(Q61L) antibodies were assessed in a subset of 302 samples utilizing tissue microarrays. The staining with the anti-BRAF(V600E) and anti-NRAS(Q61R) antibodies was diffuse, homogeneous and cytoplasmic. The anti-NRAS(Q61L) antibody displayed variable intensity staining, ranging from weak to strong in NRAS(Q61L) mutant tumours. The sensitivity and specificity for anti-BRAF(V600E) was 100 and 99.3%, anti-NRAS(Q61R) was 100 and 100% and anti-NRAS(Q61L) was 82.6 and 96.2%, respectively.CONCLUSIONS:
The use of IHC is a fast, efficient and cost-effective method to identify single specific mutations in melanoma patients. BRAF(V600E) and NRAS(Q61R) antibodies have high sensitivity and specificity; however, the NRAS(Q61L) antibody appears less sensitive. IHC can help to facilitate the timely, appropriate selection and treatment of metastatic melanoma patients with targeted therapies. Detection of melanoma-associated mutations by IHC may also provide evidence for a diagnosis of melanoma in metastatic undifferentiated neoplasms lacking expression of melanoma antigens.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Análisis Mutacional de ADN
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Proteínas Proto-Oncogénicas B-raf
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GTP Fosfohidrolasas
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Melanoma
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Proteínas de la Membrana
Tipo de estudio:
Diagnostic_studies
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Guideline
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Prognostic_studies
Límite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Histopathology
Año:
2016
Tipo del documento:
Article
País de afiliación:
Australia
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM