Abstract P3-10-34: HER2 Testing by FISH: Discordance between HER2 Signals Per Cell and HER2:CEP 17 Ratio

Abstract

Background: HER2 gene amplification status may be tested by FISH using either HER2 signals per cell or HER2:CEP17 ratio. Established HER2 testing CAP/ASCO reporting guidelines allow for interpretation and reporting using either method. Both methods classify cases as amplified, not amplified or equivocal yet the two methods may yield different interpretations for the same case. We analyzed a large dataset to quantify concordance between these two testing and reporting methodologies. Materials and Methods: We collected individual cell HER2 and CEP17 counts in 32,116 tumor cells from 1329 consecutive breast cancer cases. Data from Excel counting sheets were imported to a SQL Server database for analysis and statistics; histograms and analyses were also performed in Excel. We specifically computed concordances between methods for HER2 signals per cell and HER2:CEP17 ratio reporting. Results: Concordance between HER2 signals per cell and HER2:CEP17 ratio case averages was 89.8%. Most discordances involved cases classified as equivocal by either method. 7.8% of cases reported by HER2 signals per cell and 4.0% of cases reported by HER2:CEP17 ratio were classified as equivocal. 1% of cases were amplified by one method and not amplified by the other. Discussion: This very large dataset shows that HER2 FISH reporting by established CAP/ASCO guidelines is generally concordant between the two testing methods. However, a substantial number of cases are discordant and patient treatment could vary depending on reporting criteria used. These results indicate the need for reporting by both methods to prevent missing patients who could potentially benefit from HER2 targeted therapy. Further study is necessary to determine the most clinically relevant reporting method and criteria. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-34.