title: Divisional role of quantitative HER2 testing in breast cancer.
abstract: BACKGROUND
  Human epidermal growth factor receptor 2 (HER2) is amplified in human breast cancers in which therapy targeted to HER2 significantly improves patient outcome. We re-visited the use of real-time quantitative polymerase chain reaction (qPCR)-based assays using formalin-fixed paraffin-embedded (FFPE) tissues as alternative methods and investigated their particular clinical relevance.
  
  
  METHODS
  DNA and RNA were isolated from FFPE specimens and HER2 status was assessed by qPCR in 249 consecutive patients with primary breast cancer. Concordance with results forg immunohistochemistry (IHC) and in situ hybridization (ISH), clinical characteristics and survival was assessed.
  
  
  RESULTS
  HER2 gene copy number had a stronger correlation with clinicopathological characteristics and excellent concordance with IHC/ISH results (Sensitivity: 96.7 %; concordance: 99.2 %). HER2 gene expression showed inadequate sensitivity, rendering it unsuitable to determine HER2 status (Sensitivity: 46.7 %; concordance: 92.1 %), but lower HER2 gene expression, leading to the classification of many cases as "false negative", contributed to a prediction of better prognosis within the HER2-amplified subpopulation.
  
  
  CONCLUSIONS
  Quantitative HER2 assessments are suggested to have evolved their accuracy in this decade, which can be a potential alternative for HER2 diagnosis in line with the in situ method, while HER2 gene expression levels could provide additional information regarding prognosis or therapeutic strategy within a HER2-amplified subpopulation.
authors.affiliation: The Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Yamamoto-Ibusuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Peifen
authors.initials: P
authors.lastname: Fu
authors.forename: Satoko
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Saori
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Yumi
authors.initials: Y
authors.lastname: Honda
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Iyama
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Iwase
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005188:False Negative Reactions; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D016612:Paraffin Embedding; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human