Genetic aberrations in primary esophageal melanomas: molecular analysis of c-KIT, PDGFR, KRAS, NRAS and BRAF in a series of 10 cases

Mod Pathol. 2011 Apr;24(4):495-501. doi: 10.1038/modpathol.2010.220. Epub 2010 Dec 3.


We present a series of 10 primary esophageal melanomas of Caucasian patients characterized clinicopathologically and on the molecular level. Mutation analysis for c-Kit (exons 9, 11, 13 and 17), PDGFR (exons 12, 14 and 18), NRAS and KRAS were determined using PCR and direct sequencing. Analysis of the V600E mutation of BRAF was performed using mutation-specific PCR. Expression of c-Kit and PDGFR-A was additionally determined using immunohistochemistry. One tumor harbored a missense mutation in the c-Kit (p.F504L) and in the KRAS gene (p.G12S). A different c-Kit mutation (c.1507_1508 ins TTGCCT) was detected in another case. A third case had a V600E BRAF mutation. Using immunohistochemistry, c-Kit expression could be detected in all cases. The two cases with c-Kit mutations showed high c-Kit expression. None of the tumors showed a PDGFR mutation or expression or a NRAS mutation. We conclude that molecular analysis can identify targets for a specific therapy such as tyrosin kinase inhibitors as additional treatment option in these highly malignant tumors.

MeSH terms

  • Aged
  • DNA Mutational Analysis
  • Esophageal Neoplasms / chemistry
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / ethnology
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • European Continental Ancestry Group / genetics
  • Exons
  • Female
  • Germany
  • Humans
  • Immunohistochemistry
  • Male
  • Melanoma / chemistry
  • Melanoma / drug therapy
  • Melanoma / ethnology
  • Melanoma / genetics*
  • Melanoma / pathology
  • Middle Aged
  • Molecular Targeted Therapy
  • Mutation*
  • Neoplasm Staging
  • Patient Selection
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins c-kit / analysis
  • Proto-Oncogene Proteins c-kit / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Receptor, Platelet-Derived Growth Factor alpha / analysis
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • ras Proteins / genetics*


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-kit
  • Receptor, Platelet-Derived Growth Factor alpha
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins