title: Frequency of chromosome 17 polysomy in relation to CEP17 copy number in a large breast cancer cohort.
abstract: Eligibility to anti-HER2 therapy for breast tumors strictly depends on demonstrating HER2 overexpression (by immunohistochemistry) or HER2 gene amplification by in situ hybridization (ISH), usually defined by the ratio of HER2 gene to chromosome 17 centromere (CEP17) copies. However, the CEP17 copy number increase (CNI) has been proven responsible for misleading HER2 FISH results and recent small cohort studies suggest that chromosome 17 polysomy is actually very rare. Here we investigated by FISH the frequency of true chromosome 17 polysomy in a consecutive cohort of 5,477 invasive breast cancer patients. We evaluated and selected the LSI 17p11.2 probe for chromosome 17 enumeration on a training cohort of 67 breast cancer samples (CEP17 ≥ 2.5). LSI 17p11.2 was used in the 297/5,477 patients from the validation cohort displaying CEP17 CNI (CEP17 ≥ 3.0). Using HER2/17p11.2 scoring criteria, 37.3%/1.5% patients initially classified as equivocal/non-amplified were reclassified as amplified. For a more accurate assessment of chromosome 17 and ploidy in the samples, we tested six markers located on chromosome 17 and centromeric regions of chromosome 8 (CEP8) and 11 (CEP11) in 67 patients with CEP17 and LSI 17p11.2 CNI. True polysomy (hyperdiploidy) according to these markers was found in 0.48% of cases (24/5,020). CEP8 and CEP11 CNI (≥3.0) was more frequent in the hyperdiploid than CEP17 non-polysomic group (55.6% vs. 6.1% and 25% vs. 2.3%, respectively). Our results suggest that chromosome 17 polysomy is a rare event found in <1% breast cancer cases and that polysomy of other chromosomes frequently occurs with chromosome 17 polysomy.
authors: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 775 15 Olomouc, the Czech Republic.
authors: Vladimira
authors: V
authors: Koudelakova
authors: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 775 15 Olomouc, the Czech Republic.
authors: Radek
authors: R
authors: Trojanec
authors: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 775 15 Olomouc, the Czech Republic.
authors: Jana
authors: J
authors: Vrbkova
authors: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 775 15 Olomouc, the Czech Republic.
authors: Sandra
authors: S
authors: Donevska
authors: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 775 15 Olomouc, the Czech Republic.
authors: Katerina
authors: K
authors: Bouchalova
authors: Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 3, 775 15 Olomouc, the Czech Republic.
authors: Zdenek
authors: Z
authors: Kolar
authors: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 775 15 Olomouc, the Czech Republic.
authors: Lakshman
authors: L
authors: Varanasi
authors: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 775 15 Olomouc, the Czech Republic.
authors: Marian
authors: M
authors: Hajduch
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence