Rapid BRAF Mutation Testing in Pigmented Melanomas

Am J Dermatopathol. 2020 May;42(5):343-348. doi: 10.1097/DAD.0000000000001592.

Abstract

BRAF mutations are present in ∼40%-60% of melanomas, and targeted therapy in advanced-stage melanoma is associated with improvement in overall and progression-free survival. Accordingly, BRAF mutation determination is standard-of-care in metastatic melanoma, and a rapid, accurate assay is desirable. Melanin can present unique challenges due to inhibition of the polymerase chain reaction. The novel cartridge-based Idylla platform offers rapid molecular oncology testing; however, a formal evaluation of the impact of melanin on testing heretofore has not been explored. In this study, we evaluated the performance of Idylla BRAF mutation detection in 23 melanomas including resections, small biopsies, and cytology cell blocks. Pathologists assigned each case a pigment score from 0 to 2 based on extent of melanin content. Samples with a pigment score of 2 were successfully resulted, thus demonstrating that high melanin content did not inhibit the assay. Sensitivity and specificity of BRAF mutation detection were 100% compared with reference laboratory testing. Tissue input requirements were low, with the Idylla successfully detecting a BRAF mutation in cell block material containing only ∼400 tumor cells. The assay was simple and quick to perform, with total hands-on time of 5-10 minutes and instrument time ∼90 minutes. In summary, the Idylla BRAF mutation assay provides rapid, robust testing for melanomas with high melanin content, including samples with limited material. The assay requires minimal technical expertise, making mutation status determination accessible in a range of clinical laboratory settings. The total assay time of <2 hours facilitates prompt results to guide patient care decisions.

MeSH terms

  • DNA Mutational Analysis / methods*
  • Humans
  • Melanoma / genetics*
  • Melanoma, Cutaneous Malignant
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics*
  • Real-Time Polymerase Chain Reaction / methods*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Skin Neoplasms / genetics*

Substances

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