Abir A. Muftah
Further evidence to support bimodality of oestrogen receptor expression in breast cancer
Muftah, Abir A.; Aleskandarany, Mohammed; Sonbul, Sultan N.; Nolan, Christopher C.; Diez Rodriguez, Maria; Caldas, Carlos; Ellis, Ian O.; Green, Andrew R.; Rakha, Emad A.
Sultan N. Sonbul
Christopher C. Nolan
Maria Diez Rodriguez
Professor IAN ELLIS IAN.ELLIS@NOTTINGHAM.AC.UK
Professor of Cancer Pathology
ANDREW GREEN firstname.lastname@example.org
EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology
Aims: Although oestrogen receptor (ER)‐negative breast cancers (BCs) do not respond to hormone therapy, the response of ER‐positive BCs is reported to be variable, which may suggest a dose‐dependent effect. The aim of this study was to assess the pattern of ER expression in BCs at the protein (immunohistochemistry) and transcriptome (microarray‐based gene expression) levels.
Methods and results: ER immunohistochemical (IHC) expression was assessed in a large series of BCs, including 3649 core biopsies and 1892 cases prepared as tissue microarrays (TMAs) stained with specific antibodies. ESR1 mRNA expression was assessed in the METABRIC study (1980 cases), by the use of the Linear Models for Microarray Data (limma) software, and the results were compared with protein levels. IHC data confirmed the bimodality of ER expression, with 92.2% and 89.2% of the cases showing completely negative (less than 1%) or highly positive (≥70%) expression on the cores and TMAs, respectively. Weakly positive cases (1–10%) and intermediately positive (11–69%) cases were infrequent (2.7% and 5.1%, and 1.6% and 9.2%, in cores and TMAs, respectively), and did not show survival difference from ER‐negative tumours. When full‐face sections of the corresponding excision specimens were immunostained, 47% of the ER‐low/intermediate group were deemed to be ER‐negative. Transcriptomic data not only showed a significant correlation between ESR1 mRNA and protein expression levels, but also confirmed the bimodality of ER expression at the mRNA level.
Conclusions: Our study provides further evidence that ER expression is bimodal, and that it is observed at both the mRNA and protein levels. The reported poor survival of BC patients with low ER expression in the early clinical trials may be related to the inclusion of ER‐negative cases.
Muftah, A. A., Aleskandarany, M., Sonbul, S. N., Nolan, C. C., Diez Rodriguez, M., Caldas, C., …Rakha, E. A. (2017). Further evidence to support bimodality of oestrogen receptor expression in breast cancer. Histopathology, 70(3), 456-465. https://doi.org/10.1111/his.13089
|Journal Article Type||Article|
|Acceptance Date||Sep 16, 2016|
|Online Publication Date||Sep 20, 2016|
|Publication Date||Feb 28, 2017|
|Deposit Date||Oct 15, 2018|
|Publicly Available Date||Oct 18, 2018|
|Peer Reviewed||Peer Reviewed|
ER Bimodal Expression In Breast Cancer 9.9
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