BRAF V600E mutation and the tumour suppressor IGFBP7 in atypical genital naevi

Br J Dermatol. 2010 Mar;162(3):677-80. doi: 10.1111/j.1365-2133.2009.09558.x. Epub 2009 Nov 16.

Abstract

Background: Atypical genital naevi (AGN) are naevi of special sites with atypical histological features that overlap with those of malignant melanoma. Activating BRAF mutations, identified in the majority of banal melanocytic naevi and cutaneous melanomas, are reportedly uncommon in naevomelanocytic proliferations in nonsun-exposed sites. We have recently shown that constitutive activation of the BRAF-MEK-ERK signalling pathway in oncogenic BRAF-positive naevi increases expression and secretion of IGFBP7, which induces senescence and apoptosis.

Objectives: To ascertain the frequency of BRAF V600E mutations in AGN compared with banal naevi without atypia. An additional aim was to assess the expression of IGFBP7 in oncogenic BRAF-positive AGN.

Methods: Genomic DNA was isolated per protocol from seven genital naevi without atypia and 13 AGN for BRAF genotyping. Immunohistochemical staining for IGFBP7 was performed on all cases.

Results: The BRAF V600E mutation was identified in 43% of genital naevi without atypia and 23% of AGN (P = 0.61). In both groups, IGFBP7 expression was maintained in 67% of BRAF V600E-positive cases.

Conclusions: The prevalence of BRAF V600E in AGN suggests that ultraviolet exposure is not essential for generating the mutation. The BRAF V600E mutational status appears to be of limited diagnostic utility in distinguishing genital naevi that exhibit atypia from those that do not. Similar to oncogenic BRAF-positive common naevi without atypia, enhanced expression of the tumour suppressor IGFBP7 in oncogenic BRAF-positive AGN supports that they are biologically inert.

MeSH terms

  • Adolescent
  • Adult
  • Dysplastic Nevus Syndrome / genetics*
  • Female
  • Genes, Tumor Suppressor
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics
  • Proto-Oncogene Proteins B-raf / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Young Adult

Substances

  • Insulin-Like Growth Factor Binding Proteins
  • Tumor Suppressor Proteins
  • insulin-like growth factor binding protein-related protein 1
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf