Precise ERBB2 copy number assessment in breast cancer by means of molecular inversion probe array analysis
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Matthias Christgen1, Jana L. van Luttikhuizen2, Mieke Raap1, Peter Braubach1, Lars Schmidt1, Danny Jonigk1, Friedrich Feuerhake1, Ulrich Lehmann1, Brigitte Schlegelberger2, Hans H. Kreipe1, Doris Steinemann2
1Institute of Pathology, Hannover Medical School, Hannover, Germany
2Institute of Human Genetics, Hannover Medical School, Hannover, Germany
Doris Steinemann, email: [email protected]
Keywords: HER2/ERBB2, OncoScan, breast cancer, copy number profiling, next generation sequencing
Received: July 02, 2016 Accepted: September 19, 2016 Published: October 03, 2016
HER2/ERBB2 amplification/overexpression determines the eligibility of breast cancer patients to HER2-targeted therapy. This study evaluates the agreement between ERBB2 copy number assessment by fluorescence in situ hybridization, a standard method recommended by the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP), and newly available DNA extraction-based methods. A series of n=29 formalin-fixed paraffin-embedded breast cancers were subjected to ERBB2 copy number assessment by fluorescence in situ hybridization (FISH, Vysis, Abbott). Following macrodissection of invasive breast cancer tissue and DNA extraction, ERBB2 copy number was also determined by molecular inversion probe array analysis (MIP, OncoScan, Affymetrix) and next generation sequencing combined with normalized amplicon coverage analysis (NGS/NAC, AmpliSeq, Ion Torrent). ERBB2 copy number values obtained by MIP or NGS/NAC were tightly correlated with ERBB2 copy number values obtained by conventional FISH (rs = 0.940 and rs = 0.894, P < 0.001). Using ASCO/CAP guideline-conform thresholds for categorization of breast cancers as HER2-negative, equivocal or positive, nearly perfect concordance was observed for HER2 classification by FISH and MIP (93% concordant classifications, κ = 0.87). Substantial concordance was observed for FISH and NGS/NAC (83% concordant classifications, κ = 0.62). In conclusion, MIP facilitates precise ERBB2 copy number detection and should be considered as an ancillary method for clinical HER2 testing.
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