ArticlePloS one2013
Tumor homogeneity between primary and metastatic sites for BRAF status in metastatic melanoma determined by immunohistochemical and molecular testing.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- High-resolution melting analysis for accurate detection of BRAF mutations: a systematic review and meta-analysis.Scientific reports · 2014Pooled it
- Immunohistochemistry for Skin Cancers: New Insights into Diagnosis and Treatment of Melanoma.Cancers · 2025Review
- Comparative efficiency of differential diagnostic methods for the identification of BRAF V600E gene mutation in papillary thyroid cancer (Review).Experimental and therapeutic medicine · 2024Review
- BRAF V600E Mutation in Malignant Melanoma-A Romanian Research Experience.Medicina (Kaunas, Lithuania) · 2024Article
- The Contribution of Evolutionary Game Theory to Understanding and Treating Cancer.Dynamic games and applications · 2022Review
- Predictive Evaluation on Cytological Sample of Metastatic Melanoma: The Role of BRAF Immunocytochemistry in the Molecular Era.Diagnostics (Basel, Switzerland) · 2021Article
- BRAF Heterogeneity in Melanoma.Current treatment options in oncology · 2021Review
- VE1 immunohistochemistry is an adjunct tool for detection of BRAFJournal of clinical laboratory analysis · 2021Article
- Positive Association Between Location of Melanoma, Ultraviolet Signature, Tumor Mutational Burden, and Response to Anti-PD-1 Therapy.JCO precision oncology · 2021Article
- Metastatic Melanoma Patient-Derived Xenografts Respond to MDM2 Inhibition as a Single Agent or in Combination with BRAF/MEK Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Concordance and Discordance Rates of V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (JMA journal · 2020Article
- Immunohistochemical BRAF V600E Expression and Intratumor BRAF V600E Heterogeneity in Acral Melanoma: Implication in Melanoma-Specific Survival.Journal of clinical medicine · 2020Article
- Intra-patient Heterogeneity of BRAF and NRAS Molecular Alterations in Primary Melanoma and Metastases.Acta dermato-venereologica · 2020Article
- Article
- Intra- and Inter-TumorInternational journal of molecular sciences · 2019Article
- Immunohistochemical and Molecular Features of Melanomas Exhibiting Intratumor and Intertumor Histomorphologic Heterogeneity.Cancers · 2019Article
- An analysis of genetic heterogeneity in untreated cancers.Nature reviews. Cancer · 2019Review
- Budget Impact of Dabrafenib and Trametinib in Combination as Adjuvant Treatment of BRAF V600E/K Mutation-Positive Melanoma from a U.S. Commercial Payer Perspective.Journal of managed care & specialty pharmacy · 2019Article
- Dynamic and unpredictable changes in mutant allele fractions of BRAF and NRAS during visceral progression of cutaneous malignant melanoma.BMC cancer · 2019Article
- Comparison of droplet digital PCR and direct Sanger sequencing for the detection of the BRAFJournal of clinical laboratory analysis · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BRAF inhibitors have demonstrated improvement of overall survival in patients with metastatic melanoma and BRAF(V600) mutations. In order to evaluate BRAF tumor heterogeneity between primary and metastatic site, we have evaluated the performance of immunohistochemistry (IHC) with an anti-BRAF(V600E) antibody in both localization by comparison with high resolution melting analysis followed by Sanger sequencing in a parallel blinded study. A total of 230 samples distributed as primary melanoma (n = 88) and different types of metastatic samples (n = 142) were studied in 99 patients with advanced or metastatic melanoma (stage III or IV). The prevalence of each BRAF mutation was c.1799T>A, BRAF(V600E) (45.2%), c.1799_1800TG>AA, BRAF(V600E2) (3.0%), c.1798_1799GT>AA, BRAF(V600K) (3.0%), c.1801 A>G, BRAF(K601E) (1.3%), c.1789_1790CT>TC, BRAF(L597S) (0.4%), c.1780G>A, BRAF(D594N) (0.9%) respectively. IHC was positive in 109/112 samples harboring BRAF(V600E/E2) mutations and negative in other cases. The cytoplasmic staining was either strongly positive in tumor cells of BRAF(V600E) mutated cases. It appeared strong brown, different from the vesicular grey cytoplasmic pigmentation of melanophages. Concordance between the two techniques was 96.4%. Sensitivity of IHC for detecting the BRAF(V600E/E2) mutations was 97.3%, while specificity was 100%. Both our IHC and molecular study demonstrated homogeneity between primary and metastatic sites for BRAF status in melanoma. This study also provides evidence that IHC may be a cost-effective first-line method for BRAF(V600E) detection. Thereafter, molecular techniques should be used in negative, ambiguous or non-contributive cases.
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