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J Pathol. 2012 May;227(1):1-3. doi: 10.1002/path.3999. Epub 2012 Mar 19.

ESR1 amplification in breast cancer: controversy resolved?


The determination of oestrogen receptor α (ERα) expression in breast cancers has been for many years the standard of care for guiding patient management. In 2007, Holst and colleagues published the previously unappreciated observation that the ERα gene, ESR1, was amplified in 21% of breast cancers, and that ESR1 gene amplification identified those individuals with high ERα expression in their tumours and who were likely to respond to hormonal manipulation. This has been a controversial area. Others have tried to reproduce these findings but the results have been mixed with respect to amplification frequency, and even contradictory with respect to prognostic and predictive value. The controversy may have now been resolved. Ooi et al, in this issue of the journal, show that the large clustered FISH signals that have been interpreted as ESR1 amplification are sensitive to RNase treatment, indicating that FISH is detecting accumulation of ESR1 transcripts in the nucleus of breast cancer cells expressing high levels of ERα, rather than gene amplification events. This story has important lessons for translational cancer research, and in particular FISH studies of gene copy number.

Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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