title: Prognostic value of BRAF(V⁶⁰⁰) mutations in melanoma patients after resection of metastatic lymph nodes.
abstract: OBJECTIVE
  BRAF (V600) mutations are frequent in melanomas, and BRAF(V600)-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ≥2 mm according to BRAF (V600) mutations and other previously reported prognostic criteria.
  
  
  METHODS
  This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF (V600) mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60 % melanoma cells.
  
  
  RESULTS
  BRAF mutations (p.V600E and p.V600K in 83 and 14 % of cases, respectively) were detected in 40 % of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3 %, with a median OS of 1.4 and 2.8 years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P = 0.005, hazard ratio 2.2, 95 % confidence interval 1.3-3.9) and BRAF status (P = 0.005, hazard ratio 1.9, 95 % confidence interval 1.2-3.1).
  
  
  CONCLUSIONS
  BRAF (V600) status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.
authors: Department of Pathology, Ambroise Paré Hospital, Boulogne, France.
authors: Stéphanie
authors: S
authors: Moreau
authors: Philippe
authors: P
authors: Saiag
authors: Philippe
authors: P
authors: Aegerter
authors: Daphné
authors: D
authors: Bosset
authors: Christine
authors: C
authors: Longvert
authors: Zofia
authors: Z
authors: Hélias-Rodzewicz
authors: Cristi
authors: C
authors: Marin
authors: Frédérique
authors: F
authors: Peschaud
authors: Sophie
authors: S
authors: Chagnon
authors: Utte
authors: U
authors: Zimmermann
authors: Thierry
authors: T
authors: Clerici
authors: Jean-François
authors: JF
authors: Emile
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf