Assessment of clinical parameters associated with mutational status in metastatic malignant melanoma: a single-centre investigation of 141 patients

Schlaak, Max; Bajah, A.; Podewski, T.; Kreuzberg, Nicole; Bartenwerffer, W. von; Wardelmann, Eva; Merkelbach‐Bruse, Sabine; Büttner, Reinhard; Mauch, Cornelia; Kurschat, Peter

doi:10.1111/bjd.12140

Cited by 23 publications

(21 citation statements)

References 47 publications

(156 reference statements)

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“…We observed a correlation between BRAF mutations and being young at the time of primary melanoma diagnosis and an young age at diagnosis of the first metastasis, correlations previously reported [15][16][17][18][19] not confirmed in the meta-analysis by Lee et al 3 The high prevalence of BRAF mutations in young patients (median ages of 57 and 54 years in the retrospective and prospective cohorts respectively) may be linked to BRAF's role as 'strong' oncogenic driver, role attested by its presence in 80% of nevi, 20 meaning that fewer successive mutational events over a shorter time period are in such lesions required for the formation of a melanoma. This correlation currently appears to be specific to melanoma.…”

Section: Discussionsupporting

confidence: 82%

Prognostic and predictive values of oncogenic BRAF, NRAS, c‐KIT and MITF in cutaneous and mucous melanoma

Pracht

Mogha

Lespagnol

et al. 2015

Acad Dermatol Venereol

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Section: Discussionsupporting

confidence: 82%

Prognostic and predictive values of oncogenic BRAF, NRAS, c‐KIT and MITF in cutaneous and mucous melanoma

Pracht

Mogha

Lespagnol

et al. 2015

Acad Dermatol Venereol

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“…We also showed high interobserver agreement for scoring of the VE1 antibody staining, similar to Marin et al We showed the utility of VE1 on a variety of metastatic and primary melanomas, including different primary melanoma histologic subtypes and metastases from a variety of cutaneous, lymph node, and visceral locations. Furthermore, the VE1 immunostain was associated with younger patient age at diagnosis of the primary melanoma, supporting the association of BRAF mutated melanoma and younger age …”

Section: Discussionmentioning

confidence: 54%

“…Furthermore, the VE1 immunostain was associated with younger patient age at diagnosis of the primary melanoma, supporting the association of BRAF mutated melanoma and younger age. 27 There are several differences in our methods as compared to most previous investigators. These include the use of the Mixed Red Refine reagent from Leica Microsystems as opposed to the Ventana OptiView and Ultraview Universal DAB Detection kits.…”

Section: Discussionmentioning

confidence: 94%

Validation of the VE1 immunostain for the BRAFV600E mutation in melanoma

et al. 2014

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BACKGROUND BRAF mutation status, and therefore eligibility for BRAF inhibitors, is currently determined by sequencing methods. We assessed the validity of VE1, a monoclonal antibody against the BRAF V600E mutant protein, in the detection of mutant BRAF V600E melanomas as classified by DNA pyrosequencing. METHODS The cases were 76 metastatic melanoma patients with only one known primary melanoma who had had BRAF codon 600 pyrosequencing of either their primary (n=19), metastatic (n=57) melanoma, or both (n=17). All melanomas (n=93) were immunostained with the BRAF VE1 antibody using a red detection system. The staining intensity of these specimens was scored from 0 – 3+ by a dermatopathologist. Scores of 0 and 1+ were considered as negative staining while scores of 2+ and 3+ were considered positive. RESULTS The VE1 antibody demonstrated a sensitivity of 85% and a specificity of 100% as compared to DNA pyrosequencing results. There was 100% concordance between VE1 immunostaining of primary and metastatic melanomas from the same patient. V600K, V600Q, and V600R BRAF melanomas did not positively stain with VE1. CONCLUSIONS This hospital-based study finds high sensitivity and specificity for the BRAF VE1 immunostain in comparison to pyrosequencing in detection of BRAF V600E in melanomas.

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“…Hence, it is not surprising that available data on this topic are inconsistent but suggest a possible adverse prognostic effect for tumors harboring BRAF mutations, whether localized primary tumors, 20 regionally metastatic cases 21,22 or distant metastases are considered. [23][24][25] Further research on the topic is clearly warranted, ideally in the setting of prospective evaluations. At present, it seems premature to base decisions about prognosis solely based on BRAF mutation status.…”

Section: Prognostic Significance Of Braf Mutation In Metastatic Melanomamentioning

confidence: 99%

Frontline Approach to Metastatic BRAF-Mutant Melanoma Diagnosis, Molecular Evaluation, and Treatment Choice

Chapman

Hauschild

Sondak

2014

American Society of Clinical Oncology Educational Book

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An estimated 76,100 patients will be diagnosed with invasive melanoma in the United States in 2014, and 9,710 patients will die from the disease. In almost all cases, the cause of death is related to the development of widespread metastatic disease. Although death rates from most types of cancer have steadily decreased in the United States--a 20% decrease during two decades from a peak of 215.1 deaths per 100,000 population in 1991 to 171.8 in 2010--death rates from melanoma have steadily increased during the same time, especially among males. The news regarding melanoma is far from all bad. Increases in our understanding of the human immune system have led to the development of new immunotherapeutic drugs such as ipilimumab, which has been shown to improve survival in phase III trials in metastatic melanoma, and anti-programmed death 1 (anti-PD1) antibodies, recently hailed by ASCO as one of the past year's most noteworthy clinical cancer advances. However, no discovery has influenced and, indeed, transformed the management of metastatic melanoma more than the identifıcation of activating mutations in the BRAF gene in the mitogen-activated protein kinase (MAPK) pathway, which occur in about half of cutaneous melanomas and can be targeted with small molecule inhibitors of the BRAF protein, the downstream MEK protein, or both. This article will address how patients with metastatic melanoma are evaluated for their mutation status and how the presence of a targetable mutation influences therapeutic decisions regarding systemic therapy and even surgery.

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Assessment of clinical parameters associated with mutational status in metastatic malignant melanoma: a single-centre investigation of 141 patients

Cited by 23 publications

References 47 publications

Prognostic and predictive values of oncogenic BRAF, NRAS, c‐KIT and MITF in cutaneous and mucous melanoma

Prognostic and predictive values of oncogenic BRAF, NRAS, c‐KIT and MITF in cutaneous and mucous melanoma

Validation of the VE1 immunostain for the BRAFV600E mutation in melanoma

Frontline Approach to Metastatic BRAF-Mutant Melanoma Diagnosis, Molecular Evaluation, and Treatment Choice

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