title: HER-2 fluorescence in situ hybridization: results from the survey program of the College of American Pathologists.
abstract: BACKGROUND
  Fluorescence in situ hybridization (FISH) is a common method used to determine HER-2 status in breast cancer. Limited information is available concerning reproducibility of FISH in determining HER-2 gene amplification.
  
  
  OBJECTIVE
  To present proficiency testing results of FISH for HER-2 conducted by the Cytogenetics Resource Committee of the College of American Pathologists/American College of Medical Genetics.
  
  
  METHODS
  During the past 5 years, unstained sections from 9 invasive breast carcinomas were used for HER-2 FISH proficiency testing, allowing for comparison of FISH results among a large number of laboratories. Additional data were collected using an educational (ungraded) challenge and supplemental questions in the surveys.
  
  
  RESULTS
  The number of laboratories participating in HER-2 FISH proficiency testing has increased steadily during the past 5 years (from 35 in 2000 to 139 in 2004). Reproducibility of test results among laboratories was excellent for breast tumors with low copy number (no HER-2 amplification) and for breast tumors with high copy number (HER-2 amplification). However, there was considerable variation in interpretation of results for a tumor with low-level HER-2 amplification that was tested on 2 separate occasions. Responses to supplemental questions indicated that there was a need for consensus on the use of a separate equivocal/borderline interpretative category and the need for standardization of cutoff values used to define interpretative categories.
  
  
  CONCLUSIONS
  The College of American Pathologists proficiency survey programs provide useful information concerning the reproducibility of clinical testing for HER-2 by FISH and reflect clinical interpretation of HER-2 FISH analyses from laboratories across the country.
authors.affiliation: Department of Pathology, University of Kansas Medical Center, Kansas City, KS 66160, USA. dpersons@kumc.edu
authors.forename: Diane L
authors.initials: DL
authors.lastname: Persons
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Tubbs
authors.forename: Linda D
authors.initials: LD
authors.lastname: Cooley
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Dewald
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Dowling
authors.forename: Emma
authors.initials: E
authors.lastname: Du
authors.forename: James T
authors.initials: JT
authors.lastname: Mascarello
authors.forename: Kathleen W
authors.initials: KW
authors.lastname: Rao
authors.forename: Kathleen S
authors.initials: KS
authors.lastname: Wilson
authors.forename: Daynna J
authors.initials: DJ
authors.lastname: Wolff
authors.forename: Gail
authors.initials: G
authors.lastname: Habegger-Vance
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D020732:Cytogenetic Analysis / Q000379:methods / Q000592:standards*; D003625:Data Collection; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000592:standards*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D012955:Societies, Medical; D014481:United States
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases