title: Malignant Melanoma of Vulva and Vagina: A Histomorphological Review and Mutation Analysis--A Single-Center Study.
abstract: OBJECTIVE
  The aim of this work was to determine molecular characteristics and specifically, the frequency of BRAF, C-KIT, and NRAS mutations in vulvar and vaginal melanomas.
  
  
  METHODS
  A retrospective review of all cases of vulvar and vaginal melanoma between 2002 and 2013 was performed. We reviewed the clinical and histological characteristics of all cases and performed genotyping studies on cases that had tissue available for the study, using next-generation sequencing.
  
  
  RESULTS
  We identified 33 vulvar and 11 vaginal melanomas in women with mean ages 58 and 61 years, respectively. Next-generation sequencing analysis on 20 cases (15 vulvar and 5 vaginal) identified a BRAF mutation in 7.6%, C-KIT mutation in 27.6%, NRAS mutation in 27.6%, and TP53 mutation in 7.6% of the vulvar cases. We detected only a single TP53 mutation in the vaginal cases. We did not identify any statistically significant relationship between the mutation status and patients' outcome, depth of invasion, ulceration, stage at presentation, or lymph node metastasis.
  
  
  CONCLUSIONS
  BRAF mutations are infrequent, whereas C-KIT and NRAS mutations are seen with higher frequency in vulvar melanomas than melanomas of other sites. These mutations can be considered as potential therapeutic targets in patients harboring them. Further studies are necessary to increase our understanding of mutational events occurring in melanoma of the lower female genital tract and their relationship with clinical parameters/outcome.
authors.affiliation: University Health Network, Toronto, Canada; University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marjan
authors.initials: M
authors.lastname: Rouzbahman
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
authors.forename: Ayman
authors.initials: A
authors.lastname: Al Habeeb
authors.forename: Marcus
authors.initials: M
authors.lastname: Butler
authors.forename: Jason
authors.initials: J
authors.lastname: Dodge
authors.forename: Stephane
authors.initials: S
authors.lastname: Laframboise
authors.forename: Joan
authors.initials: J
authors.lastname: Murphy
authors.forename: Golnar
authors.initials: G
authors.lastname: Rasty
authors.forename: Danny
authors.initials: D
authors.lastname: Ghazarian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006651:Histocytochemistry; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D014625:Vaginal Neoplasms / Q000235:genetics / Q000473:pathology*; D014846:Vulvar Neoplasms / Q000235:genetics / Q000473:pathology*; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human