Molecular and immunohistochemical characterization reveals novel BRAF mutations in metanephric adenoma

Am J Surg Pathol. 2015 Apr;39(4):549-57. doi: 10.1097/PAS.0000000000000377.

Abstract

Metanephric adenoma (MA) is a rare benign renal tumor comprised of a neoplastic proliferation of primitive metanephric tubular cells. A previous study identified BRAF V600E mutations in approximately 90% of MA and found that similar BRAF exon 15 mutations are exceedingly rare in other common renal tumors, including renal cell carcinoma and oncocytoma. A recent follow-up study has validated mutation-specific immunohistochemistry (IHC) for detection of BRAF V600E mutations in a small cohort of MA. Here, we extend these findings to a larger, independent cohort of MA, demonstrating an overall 88% sensitivity and 100% specificity for BRAF V600E IHC. In addition, we report 2 cases of MA with novel BRAF exon 15 mutations, including a V600D missense mutation and a compound V600D and K601L missense mutation. Finally, we evaluate BRAF V600E IHC in a large tissue microarray cohort of common renal tumors and find no significant expression in several renal cell carcinoma subtypes. These data support a role for BRAF V600E IHC in diagnostically challenging cases of MA and expand the spectrum of BRAF exon 15 mutations in this uncommon but unique renal neoplasm.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / enzymology
  • Adenoma / genetics*
  • Adenoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • DNA Mutational Analysis*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry*
  • Kidney Neoplasms / enzymology
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Predictive Value of Tests
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies
  • Tissue Array Analysis

Substances

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