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BRAF mutation status is an independent prognostic factor for resected stage IIIB and IIIC melanoma: Implications for melanoma staging and adjuvant therapy

European Journal of Cancer

Abstract

Background

5-year survival for melanoma metastasis to regional lymph nodes (American Joint Committee on Cancer stage III) is <50%. Knowledge of outcomes following therapeutic lymphadenectomy for stage III melanoma related to BRAF status may guide adjuvant use of BRAF/MEK inhibitors along with established and future therapies.

Aims

To determine patterns of melanoma recurrence and survival following therapeutic lymph node dissection (TLND) associated with oncogenic mutations.

Methods

DNA was obtained from patients who underwent TLND and had ⩾2 positive nodes, largest node >3 cm or extracapsular invasion. Mutations were detected using an extended Sequenom MelaCARTA panel.

Results

Mutations were most commonly detected in BRAF (57/124 [46%] patients) and NRAS (26/124 [21%] patients). Patients with BRAF mutations had higher 3-year recurrence rate (77%) versus 54% for BRAF wild-type patients (hazard ratio (HR) 1.8, p = 0.008). The only prognostically significant mutations occurred in BRAF: median recurrence-free (RFS) and disease-specific survival (DSS) for BRAF mutation patients was 7 months and 16 months, versus 19 months and not reached for BRAF wild-type patients, respectively. Multivariate analysis identified BRAF mutant status and number of positive lymph nodes as the only independent prognostic factors for RFS and DSS.

Conclusions

Patients with BRAF mutations experienced rapid progression of metastatic disease with locoregional recurrence rarely seen in isolation, supporting incorporation of BRAF status into melanoma staging and use of BRAF/MEK inhibitors post-TLND.

Keywords: Melanoma, Molecular diagnostic techniques, Oncogenes, Proto-oncogene proteins B-raf.

Footnotes

a Surgical Oncology Group, School of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia

b Queensland Melanoma Project, Discipline of Surgery, The University of Queensland, Princess Alexandra Hospital, Woolloongabba, QLD, Australia

c QIMR Berghofer Medical Research Institute, Oncogenomics Laboratory, Brisbane, QLD, Australia

d Department of Pathology, Princess Alexandra Hospital, Woolloongabba, QLD, Australia

lowast Corresponding author at: School of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia. Tel: +61 738477133; fax: +61 733465598.