KIT mutations and CD117 overexpression are markers of better progression-free survival in vulvar melanomas

Br J Dermatol. 2017 Nov;177(5):1376-1384. doi: 10.1111/bjd.15836. Epub 2017 Nov 5.

Abstract

Background: Few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas.

Objectives: To evaluate the clinicopathological features of 95 cases of vulvar melanoma.

Methods: p53, CD117, Ki-67, neurofibromin, brafv600e and nrasq61r immunostains, and molecular analyses by either targeted next-generation or direct sequencing, were performed on available archival materials.

Results: Molecular testing detected mutations in KIT (44%), BRAF (25%), NF1 (22%), TP53 (17%), NRAS (9%) and TERT promoter (9%). Co-mutation of KIT and NF1 and of KIT and NRAS were identified in two and one cases, respectively. KIT mutations were significantly associated with better progression-free survival in univariate analyses. In multivariate analyses CD117 expression was significantly associated with better progression-free survival. Tumour thickness was significantly associated with worse progression-free and overall survival, and perineural invasion significantly correlated with reduced melanoma-specific survival and reduced overall survival. Cases were from multiple centres and only a subset of samples was available for molecular testing.

Conclusions: KIT mutations and CD117 overexpression are markers of better progression-free survival. In addition to its prognostic value, molecular testing may identify cases that might respond to targeted agents or immunotherapeutic approaches.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Melanoma / genetics*
  • Melanoma / mortality
  • Middle Aged
  • Mutation / genetics*
  • Prognosis
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-kit / genetics*
  • Proto-Oncogene Proteins c-kit / metabolism
  • Retrospective Studies
  • Vulvar Neoplasms / genetics*
  • Vulvar Neoplasms / mortality
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Proteins B-raf