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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.


Abir A. Muftah

Mohammed Aleskandarany

Sultan N. Sonbul

Christopher C. Nolan

Maria Diez Rodriguez

Carlos Caldas

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.

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
Journal Histopathology
Print ISSN 0309-0167
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 70
Issue 3
Pages 456-465
Public URL
Publisher URL