Emerging Concepts in the Workup of Melanoma APMG Pathologist, MD FCAP

Melanoma Leading cause of death from skin disease ~50% harbor a mutation in the BRAF gene that drives proliferation New York Times in Feb 2010 ran a three part series on a drug in trials (PLX4032) that showed dramatic results in patients with advanced melanoma The drug targets BRAF, shutting it down

August 17, 2011

Phase 3 Trial Results

BRAF and V600 BRAF gene codes for a protein in the epithelial growth factor receptor (EGFR) pathway About 50% of melanomas – Acquired mutation - the pathway is continually activated driving proliferation Most common mutation: V600E – Mutation in DNA causes change in protein amino acid sequence: Valine at amino acid 600 to GlutaminE Second common mutation: V600K – Same amino acid – Valine to Lysine

Vemurafenib (Zelboraf®) Package Insert

Testing Either primary or metastatic tissue – Formalin-fixed paraffin-embedded (FFPE) Performed using PCR – Very good analytic sensitivity - about 1% – Detects the BRAF mutation with less than 5% tumor cells in the tissue. – More sensitive than sequencing Can be significant in samples with low amount of tumor

Questions Contact pathologist with questions or to request testing on a patient: AMPG Pathologist, MD FCAP (888)

About these slides Provided by the CAP as an aid to pathologists Intended as a “starting point” from which customization / modifications can be made for personal use CAP requests to be notified when the presentation has been used via to Content has been reviewed by experts at the CAP, but does not necessarily reflect the official opinion of the College of American Pathologists. Version 1.0.1, rev. 4/26/2012 To obtain the latest version of this presentation, visit: