BRAF V600E mutational status in bile duct adenomas and hamartomas

Histopathology. 2015 Oct;67(4):562-7. doi: 10.1111/his.12674. Epub 2015 Mar 31.

Abstract

Aims: Bile duct adenomas (BDA) and bile duct hamartomas (BDH) are benign bile duct lesions considered neoplastic or secondary to ductal plate malformation, respectively. We have reported previously a high prevalence of BRAF V600E mutations detected by allele-specific polymerase chain reaction assay in BDA, and suggested that BDA may be precursors to a subset of intrahepatic cholangiocarcinomas harbouring V600E mutations. The aim of the present study was to assess the existence of BRAF V600E mutations, using immunohistochemical methods, in additional BDA as well as in BDH.

Methods and results: Fifteen BDA and 35 BDH were retrieved from the archives of the pathology departments of two French university hospitals. All cases were reviewed by two pathologists specialized in liver diseases. BRAF V600E mutational status was investigated by immunohistochemistry. Mutated BRAF mutant protein was detected in 53% of the BDA and in none of the cases of BDH.

Conclusion: Our findings suggest that BDA and BDH are different processes, and that BDA represent true benign neoplasms. They also support the hypothesis that mutated BDA might precede the development of the subset of intrahepatic cholangiocarcinomas harbouring BRAF V600E mutations.

Keywords: BRAF; V600E; bile duct adenoma; bile duct hamartoma; cholangiocarcinoma.

MeSH terms

  • Adenoma, Bile Duct / genetics*
  • Adenoma, Bile Duct / pathology
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / genetics*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / pathology*
  • Biomarkers, Tumor / genetics
  • DNA Mutational Analysis
  • Female
  • Hamartoma / genetics*
  • Hamartoma / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins B-raf / genetics*

Substances

  • Biomarkers, Tumor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf