title: Impact of polysomy 17 on HER2 testing of invasive breast cancer patients.
abstract: BACKGROUND
  Current American Society of Clinical Oncology/College of American Pathologists guidelines define HER2-positive tumors as those with >6 HER2 genes per nucleus or those with HER2/CEP17 (chromosome 17) ratio>2.2. These guidelines are potentially contradictory in tumors with polysomy of chromosome 17. The current study was performed to determine the impact of polysomy 17 on the interpretation of HER2 testing of invasive breast carcinomas.
  
  
  METHODS
  Chromosome 17 copies and HER2 gene status were identified by fluorescent in situ hybridization in 384 cases with invasive breast cancer, and the corresponding HER2 expression was obtained by immunohistochemistry stain.
  
  
  RESULTS
  The average CEP17 copy number for the group was 2.1 (range, 1.0-12.4). Forty-eight cases (13.8%, 48/348) were identified as chromosome 17 polysomy with CEP 17 copy number≥3. Ninety-two (26.4%) cases had >6 copies of HER2 per nucleus, and 92 cases (26.4%) qualified as HER2 gene amplified using the HER2/CEP17 ratio (>2.2) guideline. Polysomy 17 showed poorly positive correlations with both HER2 gene copy number and HER2 overexpression (P<0.01, r=0.338 and 0.271, respectively). The distribution of clinicopathologic parameters of Polysomy 17 tumors was more similar to HER2 negative than HER2 positive tumors.
  
  
  CONCLUSIONS
  Polysomy 17 is a crucial cause of equivocal HER2 testing results by FISH, depending on which criterion (ratio vs. absolute number) is used for interpretation. Polysomy 17 cannot be an independent predictive factor for HER2 gene amplification or protein overexpression.
authors.affiliation: Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University Yunnan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University Yunnan, China.
authors.forename: Dequan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University Yunnan, China.
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Kunming Medical University Yunnan, China.
authors.forename: Chengang
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Pathology, The Third Affiliated Hospital, Kunming Medical University Yunnan, China.
authors.forename: Zaoxiu
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University Yunnan, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University Yunnan, China.
authors.forename: Zhuangqing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University Yunnan, China.
authors.forename: Sijun
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University Yunnan, China.
authors.forename: Zhuoni
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D018734:Genes, erbB-2 / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D055815:Young Adult
keywords: Chromosome 17; breast cancer; fluorescence in situ hybridization (FISH); human epidermal growth factor receptor (HER2); immunohistochemistry (IHC); polysomy