Funding sources The CIO Köln Bonn is supported by a peer-reviewed Comprehensive Cancer Center grant from the Deutsche Krebshilfe.
CLINICAL AND LABORATORY INVESTIGATIONS
Assessment of clinical parameters associated with mutational status in metastatic malignant melanoma: a single-centre investigation of 141 patients
Article first published online: 25 MAR 2013
© 2013 The Authors. BJD © 2013 British Association of Dermatologists
British Journal of Dermatology
Volume 168, Issue 4, pages 708–716, April 2013
How to Cite
Schlaak, M., Bajah, A., Podewski, T., Kreuzberg, N., von Bartenwerffer, W., Wardelmann, E., Merkelbach-Bruse, S., Büttner, R., Mauch, C. and Kurschat, P. (2013), Assessment of clinical parameters associated with mutational status in metastatic malignant melanoma: a single-centre investigation of 141 patients. British Journal of Dermatology, 168: 708–716. doi: 10.1111/bjd.12140
Conflicts of interest None declared.
- Issue published online: 25 MAR 2013
- Article first published online: 25 MAR 2013
- Accepted for publication 23 October 2012
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.