Silver in situ hybridization (SISH) for determination of HER2 gene status in breast carcinoma: comparison with FISH and assessment of interobserver reproducibility.
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.
Papouchado
Bettina G
BG
Pathology and Laboratory Medicine Institute, Lerner College of Medicine, Cleveland Clinic, Cleveland, OH 44195, USA. papoucb@ccf.org
Myles
Jonathan
J
Lloyd
Ricardo V
RV
Stoler
Mark
M
Oliveira
Andre M
AM
Downs-Kelly
Erinn
E
Morey
Adrienne
A
Bilous
Michael
M
Nagle
Ray
R
Prescott
Nichole
N
Wang
Lin
L
Dragovich
Lidija
L
McElhinny
Abigail
A
Garcia
Carole Ferrell
CF
Ranger-Moore
Jim
J
Free
Heather
H
Powell
William
W
Loftus
Margaret
M
Pettay
James
J
Gaire
Fabien
F
Roberts
Christopher
C
Dietel
Manfred
M
Roche
Patrick
P
Grogan
Thomas
T
Tubbs
Raymond
R
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
D018030:Silver Compounds