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1.
Br J Dermatol ; 168(4): 708-16, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23528057

RESUMO

BACKGROUND: Inhibitors of the mutated, constitutively activated BRAF protein have shown efficacy in the treatment of metastatic melanoma in clinical trials. Mutation analysis especially of the BRAF, NRAS and KIT genes is essential to identify patients suitable for targeted therapies and has been introduced into routine patient care. OBJECTIVES: To correlate mutational status with clinical parameters including age, skin type, number of melanocytic naevi, primary tumour location, chronic sun damage and exposure to ultraviolet (UV) irradiation. The overall aim was to define subgroups with an increased or decreased likelihood of gene mutations. Additionally, the impact of activating BRAF mutations on clinical course was investigated. METHODS: In a single-centre, retrospective approach, mutation analysis was performed on patients with metastatic malignant melanoma. Clinical parameters were correlated with molecular findings. The total sun-burden score was assessed using a validated standardized questionnaire. RESULTS: The analysis included 141 patients with metastatic melanoma. Forty-four per cent of patients had activating BRAF mutations and were significantly younger than patients with wild-type BRAF or with NRAS mutations. KIT mutations were detected in only 3% of the patients. BRAF-mutated melanomas developed preferentially in intermittently sun-exposed areas of the body, and patients had significantly more melanocytic naevi. Once patients had progressed into stage IV disease, survival times were identical for those with BRAF-mutated and BRAF wild-type tumours. CONCLUSIONS: Mutations of the BRAF gene are correlated with younger age, a higher number of melanocytic naevi and a tumour location in intermittently UV-exposed skin. Signs of chronic photodamage are not indicative of mutational status. Patients with metastatic melanoma with BRAF mutations showed a nonsignificant tendency to progress later to stage IV disease, but once metastases were present the prognosis was identical to that with BRAF wild-type tumours.


Assuntos
Melanoma/genética , Mutação/genética , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , Análise Mutacional de DNA , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit/genética , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Luz Solar/efeitos adversos
2.
Hautarzt ; 62(6): 430-5, 2011 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-21556962

RESUMO

Basal cell carcinoma, actinic keratosis as a carcinoma in situ and squamous cell carcinoma are classified as non-melanoma epithelial skin cancers. These forms of skin cancer are thought to be the most common cancers worldwide with rising incidences. In the past years new insights into the pathogenesis of non-melanoma skin cancers have been gained. Through knowledge of the pathologic pathways, new treatment options have become available. This review summarizes the recent advantages of treatment options of non-melanoma skin cancer.


Assuntos
Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/terapia , Ceratose Actínica/terapia , Lesões Pré-Cancerosas/terapia , Neoplasias Cutâneas/terapia , Humanos
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