The Future of Molecular Analysis in Melanoma: Diagnostics to Direct Molecularly Targeted Therapy

Akabane, Hugo; Sullivan, Ryan J.

doi:10.1007/s40257-015-0159-z

Cited by 8 publications

(8 citation statements)

References 103 publications

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“…26 genes (EGFR, ALK, ROS1, BRAF, NRAS, MAP2K1, KRAS, PIK3CA, AKT1, CTNNB1, ERBB2, ERBB4, FGFR1, FGFR3, FGFR2, SMAD4, MET, NOTCH1, NTRK1, DDR2, PTEN, RET, STK11, TP53, FBXW7, UGT1A1) were identi ed by high-throughput sequencing technology (Semiconductor sequencing). Our results showed no mutation of BRAF, NRAS and MAP2K1 in this patient, which are closely associated with melanoma [9,10].…”

Section: Case Presentationsupporting

confidence: 46%

Melan-A Expression in Poorly Differentiated Carcinoma of Lung: A Potential Diagnostic Pitfall

Huang

Zhu

et al. 2021

Preprint

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BackgroundMelan-A/MART-1 is a melanocytic differentiation marker, which is recognized as an antigen on melanoma cells. It is relevant for pathologists as a useful diagnostic marker in the diagnosis of melanocytic tumors. However, the expressional pattern of Melan-A in poorly differentiated carcinoma of lung has never been reported so far.Case presentationHere, we report a 77-year-old female patient who presented with a large mass in the right lung and was subsequently diagnosed with a poorly differentiated carcinoma of lung. We unexpectedly found that the carcinoma in this patient exhibited diffuse Melan-A expression. ConclusionThis is the first case reported of a poorly differentiated carcinoma of lung with Melan-A expression. This report shows that Melan-A can express in poorly differentiated carcinoma, and highlights a potential diagnostic pitfall in the diagnosis of carcinoma, which urges pathologists to exercise caution in cases where Melan-A positivity and illustrates the need for further immunohistochemical or molecular examination to avoid misdiagnosis.

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Section: Case Presentationsupporting

confidence: 46%

Melan-A Expression in Poorly Differentiated Carcinoma of Lung: A Potential Diagnostic Pitfall

Huang

Zhu

et al. 2021

Preprint

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“…Mutations were tested preferentially in distant or lymph node metastases as heterogeneity of the mutational status between metastatic and primary tumor sites have been reported and as BRAF mutations have predictive value for the use of BRAFi and MEKi in metastatic disease [ 26 , 27 ]. If no such samples were available, analyses were performed in primaries.…”

Section: Methodsmentioning

confidence: 99%

Prognostic significance of BRAF and NRAS mutations in melanoma: a German study from routine care

Heppt

Siepmann

Engel³

et al. 2017

BMC Cancer

127

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BackgroundHotspot mutations of the oncogenes BRAF and NRAS are the most common genetic alterations in cutaneous melanoma. Specific inhibitors of BRAF and MEK have shown significant survival benefits in large phase III trials. However, the prognostic significance of BRAF and NRAS mutations outside of clinical trials remains unclear.MethodsThe mutational status of BRAF (exon 15) and NRAS (exon 2 and 3) was determined in melanoma samples of 217 patients with pyrosequencing and Sanger sequencing. The genotypes were correlated with clinical outcomes and pathologic features of the primary tumors. Time to disease progression was calculated with the cumulative incidence function. Survival analyses were performed with Kaplan-Meier estimates and Cox proportional hazards regression analysis. Relative survival was calculated with the Ederer-II method. Treatment with BRAF and MEK inhibitors and immune checkpoint blockade (ICB) was allowed.ResultsMutations in BRAF and NRAS were identified in 40.1 and 24.4% of cases, respectively. Concurrent mutations in both genes were detected in further 2.3%. The remaining 33.2% were wild type for the investigated exons (WT). BRAF mutations were significantly associated with younger age at first diagnosis (p < 0.001) and truncal localization of the culprit primary (p = 0.002). The nodular subtype was most common in the NRAS cohort. In addition, NRAS-mutant melanoma patients showed a higher frequency of nodal relapse (p = 0.013) and development of metastatic disease (p = 0.021). The time to loco-regional nodal relapse was shortest in NRAS-mutant melanoma (p = 0.002). Presence of NRAS mutation was an independent risk factor for disease progression in multivariate analysis (HR 2.01; 95% CI 1.02 – 3.98). BRAF-mutant melanoma patients showed a tendency for better overall and relative survival. Genotype was not a consistent risk factor in multivariate analysis. Instead, positive sentinel lymph node status (HR 2.65; 95% CI 1.15 – 6.10) and treatment with ICB in stage IV disease (HR 0.17; 95% CI 0.06–0.48) were significant multivariate risk factors.ConclusionsNRAS-mutant tumors tended to behave more aggressively particularly in early stages of the disease in this high-risk melanoma population. Treatment with immune checkpoint blockade improved survival in stage IV disease in a real-world setting.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3529-5) contains supplementary material, which is available to authorized users.

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“…The incidence of melanomas continues to increase at a high rate, particularly in western populations 1,2. Although melanoma represents a small proportion of skin cancers, it accounts for 75% of skin cancer deaths in the United States 3,4. The increasing rate of morbidity of melanoma is attributed mainly to its invasive potential and high resistance to many conventional therapies 5,6.…”

Section: Introductionmentioning

confidence: 99%

<p>Antitumor effects of conditioned media of human fetal dermal mesenchymal stem cells on melanoma cells</p>

BenCheng¹,

Wang²,

Pan³

et al. 2019

OTT

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Background: Malignant melanoma is the most lethal form of cutaneous tumor and has a high metastatic rate and motility capacity. Owing to the poor prognosis, it is urgent to seek an effective therapeutic regimen. Human mesenchymal stem cells (MSCs) can home to tumor cells and have been shown to play important roles in both promoting and inhibiting tumor development. Fetal dermal MSCs (FDMSCs), derived from fetal skin are a novel source of MSCs. Nevertheless, the antitumor capacity of FDMSCs on malignant melanoma is not clearly understood. Materials and methods: FDMSCs were extracted from the dorsal skin of fetal tissues. A375 melanoma cells lines were obtained from American Type Culture Collection. The effects of conditioned media from FDMSCs (CM-FDMSC) on A375 melanoma cells were tested in vivo using tumor formation assay and in vitro using cell viability, 5-ethynyl-2ʹ-deoxyuridine incorporation, flow cytometry, TdT-mediated dUTP Nick-End Labeling (TUNEL), wound healing, transwell invasion, and Western blotting. Results: CM-FDMSC inhibited A375 tumor formation in vivo. In vitro, CM-FDMSC inhibited the tumor-related activities of A375 melanoma cells, as evidenced reductions in viability, migration, and invasion. CM-FDMSC-treated A375 cells showed decreased phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) phosphorylation, and up-regulation of Bcl-2-Associated X (BAX) and down-regulation of B-cell lymphoma-2 (BCL-2) expression. Conclusion: CM-FDMSC can inhibit the tumor-forming behaviors of A375 melanoma cells and inhibit PI3K/AKT and mitogen-activated protein kinase signaling to shift their BCL-2/BAX ratio toward a proapoptotic state. Identification of the bioactive components in CM-FDMSC will be important for translating these findings into novel therapies for malignant melanoma.

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The Future of Molecular Analysis in Melanoma: Diagnostics to Direct Molecularly Targeted Therapy

Cited by 8 publications

References 103 publications

Melan-A Expression in Poorly Differentiated Carcinoma of Lung: A Potential Diagnostic Pitfall

Melan-A Expression in Poorly Differentiated Carcinoma of Lung: A Potential Diagnostic Pitfall

Prognostic significance of BRAF and NRAS mutations in melanoma: a German study from routine care

<p>Antitumor effects of conditioned media of human fetal dermal mesenchymal stem cells on melanoma cells</p>

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