title: Polysomy 17 in HER-2/neu status elaboration in breast cancer: effect on daily practice.
abstract: OBJECTIVE
  To assess the effect of chromosome 17 copy number on HER-2/neu status determination in breast cancers.
  
  
  METHODS
  HER-2/neu gene copy and chromosome 17 centromere numbers were evaluated on 893 breast carcinomas using double color fluorescence in situ hybridization (FISH). The net and chromosome 17 corrected (ratio) HER-2/neu copy numbers were compared and related to immunohistochemistry done according to the Food and Drug Administration (FDA)-approved scoring system (0, 1+, 2+, and 3+) as a first screening step in 584 cases.
  
  
  RESULTS
  When a ratio > or = 2 was considered as criterion for FISH positivity, 49.3% (440 of 893) of cases showed amplification versus 56.2% (502 of 893) by using a net HER-2/neu gene copy number >4 as a alternative criterion; 14.8% (67 of 453) of cases having a ratio <2 had a net HER-2/neu gene copy number >4 and 1.1% (5 of 440) with a ratio > or = 2 had a net HER-2/neu gene copy number <4. Among discordant cases, 88.8% (64 of 72) were polysomic (>2.25 chromosomes 17/cell) and among polysomic cases, 12.8% (40 of 312) of the low polysomic (2.26-3.75 chromosomes 17/cell) and 36.9% (24 of 65) of the highly polysomic (>3.75 chromosomes 17/cell) cases showed discordance. In cases with a ratio <2, polysomy 17 incidences were 85.7% (6 of 7) in IHC 3+, 42.4% (79 of 186) in IHC 2+, 33.3% (15 of 45) in IHC 1+, and 29.1% (16 of 55) in IHC 0.
  
  
  CONCLUSIONS
  A net increase in HER-2/neu gene copy number consecutive to polysomy 17 in the absence of specific gene amplification might lead to a strong protein overexpression in a small subset of breast carcinomas. HER-2/neu status determination by FISH is dependent on the criterion considered for positivity in clinical practice.
authors.affiliation: Pathology Department, Institut Jules Bordet, Brussels, Belgium.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Laurence
authors.initials: L
authors.lastname: Lespagnard
authors.forename: Virginie
authors.initials: V
authors.lastname: Durbecq
authors.forename: Marianne
authors.initials: M
authors.lastname: Paesmans
authors.forename: Christine
authors.initials: C
authors.lastname: Desmedt
authors.forename: Maria
authors.initials: M
authors.lastname: Gomez-Galdon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Veys
authors.forename: Fatima
authors.initials: F
authors.lastname: Cardoso
authors.forename: Christos
authors.initials: C
authors.lastname: Sotiriou
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Leo
authors.forename: Martine J
authors.initials: MJ
authors.lastname: Piccart
authors.forename: Denis
authors.initials: D
authors.lastname: Larsimont
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases