Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France)

J Eur Acad Dermatol Venereol. 2015 Dec;29(12):2436-43. doi: 10.1111/jdv.13332. Epub 2015 Sep 16.

Abstract

Background: Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment.

Objectives: We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP.

Methods: IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples.

Results: The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively.

Conclusions: This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Costs and Cost Analysis
  • Female
  • France
  • Humans
  • Immunohistochemistry* / economics
  • Melanoma / chemistry*
  • Melanoma / genetics
  • Melanoma / secondary
  • Middle Aged
  • Proto-Oncogene Proteins B-raf / analysis*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Sensitivity and Specificity
  • Sequence Analysis, DNA* / economics
  • Sequence Analysis, DNA* / methods
  • Skin Neoplasms / chemistry*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Time Factors
  • Young Adult

Substances

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