title: Polysomy 17 in breast cancer: clinicopathologic significance and impact on HER-2 testing.
abstract: OBJECTIVE
  Polysomy 17 is frequently found in breast cancer and may complicate the interpretation of HER-2 testing results. We investigated the impact of polysomy 17 on HER-2 testing and studied its clinicopathologic significance in relation to HER2 gene amplification.
  
  
  METHODS
  In 226 patients with primary invasive breast carcinoma, HER2 gene and chromosome 17 copy numbers were determined by dual-color fluorescent in situ hybridization (FISH). The interpretation of FISH results was based on either absolute HER2 gene copy number or the ratio HER2/chromosome 17. Results were correlated with HER-2 protein expression on immunohistochemistry (IHC), HER2 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR), and with various clinicopathologic parameters.
  
  
  RESULTS
  All cases with an equivocal HER-2 result by FISH, either by absolute HER2 copy number (44 of 226 patients; 19.5%) or by the ratio HER2/chromosome 17 (three of 226 patients; 1.3%), displayed polysomy 17. On its own, polysomy 17 was not associated with HER-2 overexpression on IHC or increased HER2 mRNA levels by RT-PCR. Moreover, and in contrast with HER2 gene amplification, polysomy 17 was not associated with high tumor grade, hormone receptor negativity, or reduced disease-free survival.
  
  
  CONCLUSIONS
  Polysomy 17 affects HER-2 testing in breast cancer and is a major cause of equivocal results by FISH. We show that tumors displaying polysomy 17 in the absence of HER2 gene amplification resemble more HER-2-negative than HER-2-positive tumors. These findings highlight the need for clinical trials to investigative whether polysomy 17 tumors benefit from HER-2-targeted therapy.
authors.affiliation: Department of Pathology, Katholieke Universiteit Leuven, Leuven, Belgium. isabelle.vandenbempt@uz.kuleuven.ac.be
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vanden Bempt
authors.forename: Peter
authors.initials: P
authors.lastname: Van Loo
authors.forename: Maria
authors.initials: M
authors.lastname: Drijkoningen
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
authors.forename: Ann
authors.initials: A
authors.lastname: Smeets
authors.forename: Marie-Rose
authors.initials: MR
authors.lastname: Christiaens
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.forename: Christiane
authors.initials: C
authors.lastname: De Wolf-Peeters
mesh_terms: D000782:Aneuploidy; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D018734:Genes, erbB-2 / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human