1147 - BRAF Mutations Are Frequent in Malignant Melanoma in Israeli Population and Predicts Poor Response to Biochemotherapy

Abstract

ABSTRACT Introduction Malignant melanoma is a highly-aggressive form of skin cancer. Lesions developing in non-chronically sun-damaged skin are associated with frequent activating mutations in BRAF with substitution of valine for glutamic acid at position 600 (BRAFV600E). The prognostic significance of BRAF mutation in patients with metastatic melanoma (MM) treated with chemobiotherapy is uncertain. Patients and methods We studied the prognostic significance of BRAF mutation in 69 patients with MM treated with chemobiotherapy at the Soroka Medical Center, Beer Chemobiotherapy consisted of BCNU, DTIC, cisplatin, IL-2, alpha-interferon, GM-CSF, cimetidine, and tamoxifen. Samples were micro-dissected at the molecular lab, Hacarmel hospital, and subjected to high-resolution melting analysis using primers flanking codon 600 in the BRAF gene. All abnormal high-resolution melting traces were subjected to bidirectional DNA sequencing. Results Mean age-55 years (range 25-80); Gender-male/female–41/28; Ulceration–30/54; Site of primary lesion: limbs/head/neck/trunk/retina/mucous membranes–12/13/0/14/2/3; Depth: T1/T2/T3/T4/undetermined-3/8/24/16/4; Lymph node biopsy–32/54; Lymph node involvement: none/micrometastases/metastases–14/2/16. BRAF mutation–42/69 (61%). BRAF mutation correlated with poor response to treatment (P = 0.056), but had no effect on disease-free interval (DFI). DFI was affected only by nodal stage (P = 0.026). In Cox multivariate analysis only male gender was associated with worse prognosis (P = 0.03), while BRAF mutation showed a trend towards worse prognosis (P = 0.169). Conclusions BRAF mutation in patients with MM treated with chemobiotherapy may predict poor response to treatment. Disclosure All authors have declared no conflicts of interest.