Heterogeneous expression or amplification is a challenge to HER2 diagnostics. A guideline defines heterogeneity as the presence of between 5% and 50% cells with HER2/CEP17 ratios of more than 2.20. We audited the frequency of such cells and their clinical impact in the results from 2 pathology laboratories combined with data from the TEAM [Tamoxifen vs Exemestane Adjuvant Multicentre] pathology study. HER2 reports were scanned and the percentages of amplified cells reported. Of 6,461 eligible cases, 754 (11.7%) exhibited 50% or more cells with ratios of more than 2.20, which is "amplified" by College of American Pathologists guidelines. Of the cases, 2,166 (33.5%) exhibited more than 5% but less than 50% of cells with HER2/CEP17 ratios of more than 2.20, or "heterogeneous amplification." No prognostic impact was observed when fewer than 30% of cells exhibited ratios of more than 2.20. All amplified cases with 30% to 50% of cells with ratios more than 2.20 were identified as such by United Kingdom guidelines. The percentage of tumor cells with HER2/CEP17 ratios more than 2.20 does not identify cases with heterogeneous amplification or poor outcome. A modified approach for identification of true heterogeneous amplification is suggested.

, , ,
doi.org/10.1309/AJCP0EN6AQMWETZZ, hdl.handle.net/1765/33341
American Journal of Clinical Pathology
Erasmus MC: University Medical Center Rotterdam

Bartlett, A.I, Starcyznski, J, Robson, T, MacLellan, A, Campbell, F.M, van de Velde, C.J.H, … Rea, D. (2011). Heterogeneous HER2 gene amplification: Impact on patient outcome and a clinically relevant definition. American Journal of Clinical Pathology, 136(2), 266–274. doi:10.1309/AJCP0EN6AQMWETZZ