Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: Comparison with fish and assessment of interobserver reproducibility

Bettina G. Papouchado, Jonathan Myles, Ricardo V. Lloyd, Mark Stoler, Andre M. Oliveira, Erinn Downs-Kelly, Adrienne Morey, Michael Bilous, Ray Nagle, Nichole Prescott, Lin Wang, Lidija Dragovich, Abigail McElhinny, Carole Ferrell Garcia, Jim Ranger-Moore, Heather Free, William Powell, Margaret Loftus, James Pettay, Fabien GaireChristopher Roberts, Manfred Dietel, Patrick Roche, Thomas Grogan, Raymond Tubbs

Research output: Contribution to journalArticle

73 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)767-776
Number of pages10
JournalAmerican Journal of Surgical Pathology
Volume34
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • CISH
  • Fluorescence in situ hybridization
  • HER2
  • SISH
  • Silver in situ hybridization

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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    Papouchado, B. G., Myles, J., Lloyd, R. V., Stoler, M., Oliveira, A. M., Downs-Kelly, E., Morey, A., Bilous, M., Nagle, R., Prescott, N., Wang, L., Dragovich, L., McElhinny, A., Garcia, C. F., Ranger-Moore, J., Free, H., Powell, W., Loftus, M., Pettay, J., ... Tubbs, R. (2010). Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: Comparison with fish and assessment of interobserver reproducibility. American Journal of Surgical Pathology, 34(6), 767-776. https://doi.org/10.1097/PAS.0b013e3181d96231