title: Multi-center evaluation of the novel fully-automated PCR-based Idylla™ BRAF Mutation Test on formalin-fixed paraffin-embedded tissue of malignant melanoma.
abstract: The advent of BRAF-targeted therapies led to increased survival in patients with metastatic melanomas harboring a BRAF V600 mutation (implicated in 46-48% of malignant melanomas). The Idylla(™) System (Idylla(™)), i.e., the real-time-PCR-based Idylla(™) BRAF Mutation Test performed on the fully-automated Idylla(™) platform, enables detection of the most frequent BRAF V600 mutations (V600E/E2/D, V600K/R/M) in tumor material within approximately 90 min and with 1% detection limit. Idylla(™) performance was determined in a multi-center study by analyzing BRAF mutational status of 148 archival formalin-fixed paraffin-embedded (FFPE) tumor samples from malignant melanoma patients, and comparing Idylla(™) results with assessments made by commercial or in-house routine diagnostic methods. Of the 148 samples analyzed, Idylla(™) initially recorded 7 insufficient DNA input calls and 15 results discordant with routine method results. Further analysis learned that the quality of 8 samples was insufficient for Idylla(™) testing, 1 sample had an invalid routine test result, and Idylla(™) results were confirmed in 10 samples. Hence, Idylla(™) identified all mutations present, including 7 not identified by routine methods. Idylla(™) enables fully automated BRAF V600 testing directly on FFPE tumor tissue with increased sensitivity, ease-of-use, and much shorter turnaround time compared to existing diagnostic tests, making it a tool for rapid, simple and highly reliable analysis of therapeutically relevant BRAF mutations, in particular for diagnostic units without molecular expertise and infrastructure.
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Linea
authors.initials: L
authors.lastname: Melchior
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Grauslund
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.affiliation: Oncology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Montagut
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Erica
authors.initials: E
authors.lastname: Torres
authors.affiliation: Pathology Department, Hospital del Mar, Barcelona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Moragón
authors.affiliation: Department Clinical Biology, Imelda Hospital, Bonheiden, Belgium.
authors.forename: Isabel
authors.initials: I
authors.lastname: Micalessi
authors.affiliation: Department Clinical Biology, Imelda Hospital, Bonheiden, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Frans
authors.affiliation: Department Anatomic Pathology, Imelda Hospital, Bonheiden, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Noten
authors.affiliation: Department Anatomic Pathology, Imelda Hospital, Bonheiden, Belgium.
authors.forename: Claire
authors.initials: C
authors.lastname: Bourgain
authors.affiliation: Unit Molecular Pathology, Laboratorium Pathologie Oost-Nederland, Hengelo, The Netherlands.
authors.forename: Renske
authors.initials: R
authors.lastname: Vriesema
authors.affiliation: Unit Molecular Pathology, Laboratorium Pathologie Oost-Nederland, Hengelo, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: van der Geize
authors.affiliation: Pathology Department, Jan Yperman Hospital, Ieper, Belgium.
authors.forename: Kristof
authors.initials: K
authors.lastname: Cokelaere
authors.affiliation: Pathology Department, Jan Yperman Hospital, Ieper, Belgium.
authors.forename: Nancy
authors.initials: N
authors.lastname: Vercooren
authors.affiliation: Pathology Department, Jan Yperman Hospital, Ieper, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Crul
authors.affiliation: Pathology Department, Städtischen Klinikum Karlsruhe, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rüdiger
authors.affiliation: Pathology Department, Städtischen Klinikum Karlsruhe, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Buchmüller
authors.affiliation: Biocartis NV, Mechelen, Belgium.
authors.forename: Martin
authors.initials: M
authors.lastname: Reijans
authors.affiliation: Biocartis NV, Mechelen, Belgium. Electronic address: cjans@biocartis.com.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jans
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods; D005557:Formaldehyde; D006801:Humans; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D016612:Paraffin Embedding / Q000379:methods; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000096142:Cutaneous Malignant Melanoma
chemical_list: D005557:Formaldehyde; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf