2 research outputs found
Heterogeneous HER2 Gene Amplification Impact on Patient Outcome and a Clinically Relevant Definition
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