title: Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility.
abstract: The importance of HER2 status in breast cancer management has focused attention on the ability of clinical assays to correctly assign HER2 amplification status. There is no consensus as to the best method for assessing HER2 status. Disadvantages of fluorescence in situ hybridization (FISH) testing include longer time required for staining and scoring slides, requirements for specialized training and fluorescence microscopy, and loss of the signal due to quenching of the fluorescent dye. Silver-enhanced in situ hybridization (SISH) is a rapid fully automated assay providing permanently stained slides that are interpreted by conventional bright field microscopy which enables pathologists to evaluate slides within the context of tissue morphology. This study evaluates the concordance between SISH and FISH assays in determining the status of HER2 gene amplification in a cohort of 298 primary invasive breast carcinomas. Furthermore, we assessed in detail the variables contributing to interobserver interpretive reproducibility of HER2 SISH among 10 pathologists. HER2 was quantified using the ratio of HER2 to CHR17 signals using the conventional historical interpretation scale and also by the American Society of Clinical Oncology/College of American Pathologists reporting scheme. For SISH status determined by consensus among 10 pathologists, overall concordance between SISH and FISH was identified in 288 of 298 cases (96.6%) using the conventional Food and Drug Administration approved criteria. Overall agreement was observed in 282 of 285 cases (98.9%) using the American Society of Clinical Oncology/College of American Pathologists result reporting scheme (with equivocal cases removed). In conclusion, SISH represents a novel approach for the determination of HER2 status in breast cancer. The overall concordance between SISH and FISH is excellent, and the interpretation of SISH results by pathologists is most reproducible using the HER2/CHR17 ratio.
authors.affiliation: Pathology and Laboratory Medicine Institute, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. papoucb@ccf.org
authors.forename: Bettina G
authors.initials: BG
authors.lastname: Papouchado
authors.forename: Jonathan
authors.initials: J
authors.lastname: Myles
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Lloyd
authors.forename: Mark
authors.initials: M
authors.lastname: Stoler
authors.forename: Andre M
authors.initials: AM
authors.lastname: Oliveira
authors.forename: Erinn
authors.initials: E
authors.lastname: Downs-Kelly
authors.forename: Adrienne
authors.initials: A
authors.lastname: Morey
authors.forename: Michael
authors.initials: M
authors.lastname: Bilous
authors.forename: Ray
authors.initials: R
authors.lastname: Nagle
authors.forename: Nichole
authors.initials: N
authors.lastname: Prescott
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Lidija
authors.initials: L
authors.lastname: Dragovich
authors.forename: Abigail
authors.initials: A
authors.lastname: McElhinny
authors.forename: Carole Ferrell
authors.initials: CF
authors.lastname: Garcia
authors.forename: Jim
authors.initials: J
authors.lastname: Ranger-Moore
authors.forename: Heather
authors.initials: H
authors.lastname: Free
authors.forename: William
authors.initials: W
authors.lastname: Powell
authors.forename: Margaret
authors.initials: M
authors.lastname: Loftus
authors.forename: James
authors.initials: J
authors.lastname: Pettay
authors.forename: Fabien
authors.initials: F
authors.lastname: Gaire
authors.forename: Christopher
authors.initials: C
authors.lastname: Roberts
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Patrick
authors.initials: P
authors.lastname: Roche
authors.forename: Thomas
authors.initials: T
authors.lastname: Grogan
authors.forename: Raymond
authors.initials: R
authors.lastname: Tubbs
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D015588:Observer Variation; D015203:Reproducibility of Results; D018030:Silver Compounds
chemical_list: D018030:Silver Compounds