title: Impact of oncogenic BRAF mutations and p16 expression on the growth rate of early melanomas and naevi in vivo.
abstract: BACKGROUND
  It is important to know what drives and arrests melanocytic growth in vivo but observations linking oncogenic mutations to growth rates of melanocytic neoplasms in vivo are sparse.
  
  
  OBJECTIVE
  To clarify the relationship between BRAF(V) (600E) mutations and p16 expression and the growth rate of melanocytic neoplasms in vivo.
  
  
  METHODS
  We measured the growth rate of 54 melanocytic lesions (26 melanomas, 28 naevi) in vivo with digital dermatoscopy and correlated it with BRAF(V) (600E) and p16 expression, and with dermatoscopic and histological patterns.
  
  
  RESULTS
  Melanomas grew faster than naevi (mean 2·7 vs. 0·8 mm(2) /year; P < 0·001) and the growth rate was faster in lesions with more nests (> 25% nests: 2·0 mm(2) /year vs. < 25% nests: 1·0 mm(2) /year; P = 0·036). Melanomas with the BRAF(V) (600E) mutation grew significantly faster than melanomas without the mutation (mean 3·36 vs. 1·60 mm(2) /year, P = 0·018). This effect of the BRAF(V) (600E) mutation on the growth rate was not observed in melanocytic naevi (mean 1·01 vs. 0·47 mm(2) /year, P = 0·274). Histopathologically, extensive nesting, larger nests and larger cell sizes were more common in melanocytic neoplasms with the BRAF(V) (600E) mutation than in those without the mutation. Melanomas expressing p16 had a slower growth rate than melanomas without p16 expression (2·27 vs. 4·34 mm(2) /year, P = 0·047). This effect was not observed in naevi (0·81 vs. 0·68 mm(2) /year, P = 0·836).
  
  
  CONCLUSIONS
  The expression of BRAF(V) (600E) and the loss of p16 accelerate the growth rate of early melanomas in vivo but not in melanocytic naevi. In comparison to melanocytic proliferations that lack the mutation, the epidermal melanocytes in lesions that harbour BRAF(V) (600E) mutations are larger and more frequently arranged in large nests.
authors.affiliation: Department of Dermatology, Medical University of Vienna, Währinger Güurtel 18-20, 1090, Vienna, Austria.
authors.forename: P
authors.initials: P
authors.lastname: Tschandl
authors.affiliation: Institute of Neurology, Medical University of Vienna, Währinger Güurtel 18-20, 1090, Vienna, Austria.|Department of Internal Medicine I, Medical University of Vienna, Währinger Güurtel 18-20, 1090, Vienna, Austria.
authors.forename: A S
authors.initials: AS
authors.lastname: Berghoff
authors.affiliation: Institute of Neurology, Medical University of Vienna, Währinger Güurtel 18-20, 1090, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Preusser
authors.affiliation: Department of Pathology, Medical University of Vienna, Währinger Güurtel 18-20, 1090, Vienna, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Pammer
authors.affiliation: Department of Dermatology, Medical University of Vienna, Währinger Güurtel 18-20, 1090, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Pehamberger
authors.affiliation: Department of Dermatology, Medical University of Vienna, Währinger Güurtel 18-20, 1090, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Kittler
mesh_terms: D049108:Cell Enlargement; D049109:Cell Proliferation / Q000235:genetics; D046169:Dermoscopy; D005260:Female; D019942:Genes, p16; D006801:Humans; D008297:Male; D008544:Melanocytes / Q000473:pathology*; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009508:Nevus, Pigmented / Q000235:genetics* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology
chemical_list: D048493:Proto-Oncogene Proteins B-raf