title: Determination of the Her-2/neu gene amplification status in cytologic breast cancer specimens using automated silver-enhanced in-situ hybridization (SISH).
abstract: Silver-enhanced in-situ hybridization (SISH) is an emerging tool for the determination of the Her-2/neu amplification status in breast cancer. SISH is technically comparable to fluorescence in-situ hybridization (FISH) but does not require a fluorescence microscope for its interpretation. Although recent studies on histologic evaluations of SISH are promising, we aimed to evaluate its performance on 71 cytologic breast cancer specimens with the new combined Her-2/Chr17 probe. Her-2/neu status as routinely determined by FISH was available for all patients. We found SISH signals in cytologic cell blocks and smear specimens easy to evaluate in most cases. Small numbers of tumor cells and difficulties in identifying tumor cells in lymphocyte-rich backgrounds were limiting factors. Her-2/neu status, as determined by Her-2/Chr17 SISH, was basically identical to the results of the corresponding FISH. The discrepancies were mainly owing to the heterogeneity of Her-2/neu amplification in the tumor tissue. Interobserver agreement for the SISH evaluation was high (kappa value: 0.972). We conclude that Her-2/Chr17 SISH is a useful and accurate method for the evaluation of the Her-2/neu gene amplification status in cytologic breast cancer specimens, particularly in metastatic breast cancer lesions. The advantages of signal permanency and bright-field microscopic result interpretation make this technique an attractive alternative to the current FISH-based gold standard.
authors.affiliation: Division of Cytology, Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. florian.fritzsche@usz.ch
authors.forename: Florian Rudolf
authors.initials: FR
authors.lastname: Fritzsche
authors.forename: Peter K
authors.initials: PK
authors.lastname: Bode
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Varga
authors.forename: Beata
authors.initials: B
authors.lastname: Bode
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057205:Automation, Laboratory; D044963:Biopsy, Fine-Needle; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D015203:Reproducibility of Results; D016622:Silver Staining
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human