TY - JOUR
TI - Heterogeneous HER2 Gene Amplification Impact on Patient Outcome and a
Clinically Relevant Definition
AU - Bartlett, Alastair I.
AU - Starcyznski, Jane
AU - Robson, Tammy and
AU - MacLellan, Alex
AU - Campbell, Fiona M.
AU - van de Vekle, Cornelis J. H.
AU - and Hasenburg, Annette
AU - Markopoulos, Christos
AU - Seynaeve, Caroline
AU - and Rea, Daniel
AU - Bartlett, John M. S.
JO - AMERICAN JOURNAL OF CLINICAL PATHOLOGY
PY - 2011
VL - 136
TODO - 2
SP - 266-274
PB - OXFORD UNIV PRESS INC
SN - 0002-9173
TODO - 10.1309/AJCP0EN6AQMWETZZ
TODO - HER2; Amplification; Breast; Heterogeneity
TODO - 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.
ER -