Molecular Diagnostics

British Journal of Cancer (2006) 95, 616–626. doi:10.1038/sj.bjc.6603295 www.bjcancer.com
Published online 1 August 2006

Expression of oestrogen receptor-bold italic beta in oestrogen receptor-alpha negative human breast tumours

G P Skliris1, E Leygue1, L Curtis-Snell2, P H Watson2 and L C Murphy1

  1. 1Department of Biochemistry & Medical Genetics, Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Manitoba, Canada R3E OV9
  2. 2Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada R3E OV9

Correspondence: LC Murphy, E-mail: lcmurph@cc.umanitoba.ca

Received 17 January 2006; Revised 30 May 2006; Accepted 29 June 2006; Published online 1 August 2006.

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Abstract

To analyse the phenotype of breast tumours that express oestrogen receptor-beta (ERbeta) alone tissue microarrays were used to investigate if ERbeta isoforms are associated with specific prognostic markers and gene expression phenotypes in ERalpha-negative tumours. ERalpha-negative tumours were positive for ERbeta1 in 58% of cases (n=122/210), total ERbeta in 60% (n=115/192) and ERbeta2/cx in 57% of cases (n=114/199). Oestrogen receptor-beta1 and total ERbeta were significantly correlated with Ki67 (r=0.28, P<0.0001, n=209; r=0.29, P<0.0001, n=191) and with CK5/6, a marker of the basal phenotype (r=0.20, P=0.0106, n=170; r=0.18, P=0.0223, n=158). ERbeta2/cx was strongly associated with p-c-Jun and NF-kappaBp65 (r=0.53, P<0.0001, n=93; r=0.35, P<0.0001, n=176). This study shows that a range of ERbeta isoform expression occurs in ERalpha-negative breast tumours. While expression of ERbeta1, total and ERbeta2/cx are correlated, individual forms show associations with certain phenotypes that suggest different roles in subsets of ERalpha-negative cancers. Based on our in vivo observations, ERbeta may have the potential to become a therapeutic target in the specific subcohort of ERalpha-negative breast cancers.

Keywords:

oestrogen receptor-beta isoforms, breast cancer, immunohistochemistry, proliferation, basal phenotype