title: Evaluation of HER2/neu Status by Immunohistochemistry Using Computer-Based Image Analysis and Correlation With Gene Amplification by Fluorescence In Situ Hybridization Assay: A 10-Year Experience and Impact of Test Standardization on Concordance Rate.
abstract: BACKGROUND
  The American Society of Clinical Oncology/College of American Pathologists proposed several recommendations for human epidermal growth factor receptor 2 (HER2) test standardization. One suggestion was that image analysis (IA) could be useful for scoring of HER2/neu immunohistochemistry. The utilization of IA in a real-world practice in a large cohort of cases has not been previously reported.
  
  
  OBJECTIVE
  To compare HER2/neu quantification by IA with gene amplification by fluorescence in situ hybridization (FISH); to determine sensitivity, specificity, and concordance rates with the FISH assay; and to determine association between HER2 status with estrogen receptor (ER), progesterone receptor (PR), and Ki-67 expression.
  
  
  METHODS
  We evaluated HER2 results performed by immunohistochemistry and FISH in conjunction with ER, PR, and Ki-67 in 3093 invasive breast cancer cases from 2002 to 2011.
  
  
  RESULTS
  The overall concordance between immunohistochemistry and FISH was 87.3% (1768 of 2026). When analyzed by year, there was an improvement in the positive concordance rate from 49.4% (44 of 89) to 95.0% (57 of 60) (P < .001). The negative concordance rate was at least 95% with a median false-negative rate of 1.5%. In the FISH+ group, amplification ratio showed significant correlation with IA scores (P < .001). Positive versus negative HER2 status was associated with lower ER and PR levels (P < .001) and higher Ki-67 expression (P < .001).
  
  
  CONCLUSIONS
  Scoring of HER2/neu by IA was associated with high false-positive rates before 2008. Improvement in concordance rate after 2008 may be due to proper tissue handling, improved HER2/neu scoring by IA, and assay standardization.
authors.forename: Venetia R
authors.initials: VR
authors.lastname: Sarode
authors.forename: Qun Diane
authors.initials: QD
authors.lastname: Xiang
authors.forename: Alana
authors.initials: A
authors.lastname: Christie
authors.forename: Rebecca
authors.initials: R
authors.lastname: Collins
authors.forename: Roshni
authors.initials: R
authors.lastname: Rao
authors.forename: A Marilyn
authors.initials: AM
authors.lastname: Leitch
authors.forename: David
authors.initials: D
authors.lastname: Euhus
authors.affiliation: From the Departments of Pathology (Drs Sarode, Xiang, and Collins).
authors.forename: Barbara
authors.initials: B
authors.lastname: Haley
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods / Q000592:standards*; D007150:Immunohistochemistry / Q000379:methods / Q000592:standards*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods / Q000592:standards*; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques / Q000379:methods / Q000592:standards*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human