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[180] Automated Accelerated Silver In-Situ Hybridization (SISH
) for Detection of HER2 Gene Amplification in Breast Carcinoma
BG Papouchado, E Downs-Kelly, L Pestic-Dragovich, S Hood, JD Pettay, J Myles, M Loftus, N Prescott, T Grogan, PC Roche, AS McElhinny, DJ Dabbs, WM Hanna, M Dietel, DG Hicks, R Alsabeh, WC Powell, RR Tubbs. Cleveland Clinic, Cleveland, OH; Tucson, AZ; Pittsburgh, PA; Toronto, CA; Charite 
Universitatsmedizin, Berlin, Germany; Roswell Park Cancer Institute, Buffalo, NY; Cedars-Sinai Medical Center, Los Angeles, CA
Background: Determination of HER2 status is crucial for determining management of breast carcinoma. Use of FISH as the primary method for determining HER2 status may be problematic, requiring specialized instrumentation and training. Bright field in situ hybridization is readily incorporated into surgical pathology workflow, but utility has been limited by manual methods requiring overnight hybridization.
Design: 96 invasive breast carcinomas for which FISH results were known were analyzed for HER2 and chromosome 17 (CP17) status by SISH. Challenging cases (monosomic and polysomic CP17, HER2 monoallelic deletion, genotypic heterogeneity) comprised 
20% of the evaluated cases. SISH and FISH signal enumeration was performed; HER2 gene amplification was defined as HER2/CP17 ratio 
2. SISH slides also were semiquantitatively scored as HER2 amplified, heterogeneous, or nonamplified by nine pathologists. HER2 FISH status was used as the reference standard (multiple regression analysis for spot counts, kappa for observer agreement).
Results: There was nearly perfect agreement (97.9%) between HER2 SISH and the corresponding FISH counts (R2 = 0.955, p>0.001; sensitivity 92%/specificity 100%). Interpretation of the SISH results compared with FISH were highly reproducible among the nine pathologists [average kappa 0.812 (amplified versus non amplified cases) and 0.777 (amplified and heterogeneous cases versus non amplified cases)].
Conclusions: SISH HER2 results are highly concordant with FISH, and interpretation is reproducible. SISH staining uses a fully automated protocol, a repeat free HER2 probe, a CP17 centromeric reference, and accelerated detection providing a HER2 genotype in approximately six hours. Standard bright field microscopic SISH interpretation is readily integrated into surgical pathology workflow for routine assessment of HER2 status in breast carcinoma.
Category: Breast
Wednesday, March 28, 2007
Poster # 3, Wednesday Morning