Analysis of BRAF mutation status in high-risk malignant melanoma patients having received HD IFNa therapy in adjuvant setting.

Abstract

e19020 Background: Mutation in BRAF gene is considered to be a predictor of response to vemurafenib. However, it still remains to be demonstrated wheter BRAF mutational status is a prognostic factor in high risk melanomas. Methods: Between May 2003 till July 2011, there were 100 patients with a wide local excision of high risk malignant melanoma removed, who received HD IFNa adjuvant treatment. We retrospectively analyzed the data of 57 patients, who had determined BRAF V600 mutation status by real-time PCR assay (Cobas 4800 BRAF V600 Mutation Test). 48 patients were identified as a high-risk melanoma initialy, 9 after locoregional recurrence. Results: We have analysed samples from primary tumors (N35), lymph nodes (N16) and mets (N6). BRAF V600 mutation was found in 35 cases (61.4%). The median age was 52 yrs (range 19-66 yrs) in the whole group, in the subgroup of BRAF MT/WT it was 52.5/51 yrs (nonsignificant). The female/male ratio was 22/35, with no sex dependent differences for the BRAF MT or WT. The most frequent tumor stage T4N0M0 (29.8%) was the most common indication to the IFN treatment. The recurrence (distant mets) of melanoma was observed in 33 patients (57.8%); BRAF MT/WT 21 vs 12, HR 0.74, (95%CI 0.37-1.48) p =0.25. We observed 24 deaths (42.1%); BRAF MT/WT 16 vs 8, HR 0.72 (95%CI 0.32-1.62) p =0.46. We found a statistically significant higher risk of death associated with lower age in the whole group (p =0.006; OR =0,92). Logistic regression in the subgroup of BRAF MT patients revealed that the positivity of lymph nodes was associated with 5.6-times higher probability of death (OR =0.89, p =0.094). Additionally, a higher age was significantly associated with better overall survival (OS) p=0.012. On the other hand, in the subgroup of BRAF WT patients neither the age nor the positivity of lymph nodes influenced OS. Conclusions: We confirmed that BRAF mutation occurs in approximately 60% high-risk malignant melanomas. There were no statistically significant differences in DFS or OS between BRAF MT/WT form. However, our analysis corroborates the notion that BRAF MT patients have higher risk of death or recurrence, which we consider to be clinically relevant.