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Purpose: BRAF (V600) mutations are frequent in melanomas, and BRAF(V600)-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ≥2 mm according to BRAF (V600) mutations and other previously reported prognostic criteria.
Methods: This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF (V600) mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60 % melanoma cells.
Results: BRAF mutations (p.V600E and p.V600K in 83 and 14 % of cases, respectively) were detected in 40 % of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3 %, with a median OS of 1.4 and 2.8 years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P = 0.005, hazard ratio 2.2, 95 % confidence interval 1.3-3.9) and BRAF status (P = 0.005, hazard ratio 1.9, 95 % confidence interval 1.2-3.1).
Conclusions: BRAF (V600) status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.
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http://dx.doi.org/10.1245/s10434-012-2457-5 | DOI Listing |
J Thorac Oncol
September 2025
Jusidman Cancer Center, Sheba Medical Center, Ramat Gan, Israel; Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Sci Data
September 2025
Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Baronissi, (SA), Italy.
Cutaneous melanoma (CM), with a continuously rising incidence worldwide, represents the most aggressive type of skin cancer, and it leads to the majority of skin cancer-related deaths. Approximately 50% of CM carry the activating BRAF mutation and, although BRAF inhibitors have demonstrated clinical efficacy, most patients often develop early resistance to treatment. Aberrant expression of non-coding RNAs (ncRNAs), which represent less than 2% of the entire transcriptome, has been implicated in CM development and progression.
View Article and Find Full Text PDFPharmaceuticals (Basel)
August 2025
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy.
: Melanoma, the deadliest human skin cancer, frequently harbors activating BRAF mutations, with V600E being the most prevalent. These alterations drive constitutive activation of the MAPK pathway, promoting uncontrolled cell proliferation, survival, and dissemination. The advent of BRAFi and MEKi has significantly improved outcomes in BRAF V600-mutant melanoma.
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Dermatology, University Hospital Tübingen, Tübingen, Germany.
Immune checkpoint inhibitors (ICI) have significantly improved melanoma-specific survival (MSS), particularly in patients with tumors with a high tumor mutational burden (TMB) or mutation. In the adjuvant setting, ICIs significantly improve relapse-free survival (RFS), but data on MSS are still lacking. Tissue samples from 83 patients with stage IIIC/D/IV melanoma who started adjuvant ICI between March 2018 and September 2019 were examined using a 700 gene panel.
View Article and Find Full Text PDFEur J Cancer
August 2025
Heidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, A Partnership Between DKFZ and University Hospital Heidelberg, Heidelberg, Germany. Electronic address:
Introduction: While BRAF-/MEK-inhibitor therapy is well established in V600E/K-mutated melanoma, the efficacy in advanced melanoma with rare BRAF mutations remains uncertain. This is an updated analysis of an international data collection including 49 new patients, accompanied by development of a publicly accessible global database.
Patients And Methods: A retrospective analysis was conducted at 20 international cancer centers, evaluating 143 patients with rare BRAF V600 (V600-nonE/K; 48 %) and non-V600 (52 %) mutations.