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Estrogen receptor beta 2 is associated with poor prognosis in estrogen receptor alpha-negative breast carcinoma

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Abstract

Purpose

Our aim was to examine the prognostic significance of ERbeta1 and ERbeta2 expression in ERalpha-negative breast carcinomas.

Materials and methods

We evaluated nuclear and cytoplasmic expression of ERbeta1 and ERbeta2 by immunohistochemistry in a group of 95 patients with long follow-up. ERbeta1 and ERbeta2 status was correlated with clinicopathological parameters and disease outcome. Univariate and multivariate analyses of ERbeta1 and ERbeta2 as independent markers of disease-free survival (DFS) were carried out using the Cox proportional hazards model.

Results

Nuclear ERbeta1 (nERbeta1) and nERbeta2 status was positively correlated (p = 0.01). nERbeta1 positivity was associated with low histological grade (p = 0.01) in all patients and in the nERbeta2-positive subgroup (p = 0.03) but not in the nERbeta2-negative (p = 0.27). nERbeta2 positivity was associated with lymph node involvement and tumor relapse in all cases (p < 0.00 and p < 0.00, respectively) and in the nERbeta1-negative subgroup (p < 0.00 and p < 0.00, respectively) but not in the nERbeta1-positive (p = 0.09 and p = 0.20, respectively). nERbeta2 positivity was associated with poor DFS in all patients (log-rank p <0.00), in the post-menopausal patient subgroup (log-rank p = 0.02) and in the HER2-negative (triple-negative) subgroup (log-rank p = 0.04). Cox multivariate analysis including ERbeta1, ERbeta2 and established clinicopathological variables highlighted ERbeta2 as an independent marker of early disease recurrence (hazard ratio 4.87; 95 % confidence interval 1.07–22.3; p = 0.04).

Conclusion

High nERbeta2 is an independent marker of early relapse in ERalpha-negative breast carcinoma, and in particular, in the nERbeta1-negative, the post-menopausal patient and the triple-negative subgroups. These findings suggest that inhibition of expression and/or function of ERbeta2 could improve disease outcome.

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Abbreviations

ER:

Estrogen receptor

nERβ1:

Nuclear estrogen receptor β1

nERβ2:

Nuclear estrogen receptor β2

PgR:

Progesterone receptor

IHC:

Immunohistochemistry

FFPE:

Formalin-fixed paraffin-embedded

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Acknowledgments

We thank Dr B. Steele (IBMCB-NHRF) for reviewing and editing the manuscript and Ms C. Vlachou for secretarial assistance. This research has been supported by EU European Social Fund and Greek national funds through the Operational Program “Education and Lifelong Learning” of the NSRF-Research Funding Program: Projects THALES 85355 and by the Greek Ministry of Development through grant 03ED644.

Conflict of interest

None.

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Authors and Affiliations

  1. Laboratory of Histology and Embryology, Medical School, University of Athens, 75 M. Asias str., 11527, Athens, Greece

    Νiki Ι. Chantzi, Dina G. Tiniakos & Marina Palaiologou

  2. Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48, Vassileos Constantinou Av, 11635, Athens, Greece

    Νiki Ι. Chantzi, Eugen Dhimolea, Dimitra J. Mitsiou & Μichael N. Alexis

  3. Department of Pathology, Evgenidio Infirmary, Papadiamantopoulou 20, 11528, Athens, Greece

    Nikolaos Goutas

  4. “Micromedica” Histopathology Lab, Tsoha 18, 11521, Athens, Greece

    Theodoros Filippidis

  5. “Prolipsis” Medical Centre, 3 Sevastias Str, Athens, Greece

    Stamatis D. Vassilaros

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  1. Νiki Ι. Chantzi
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  2. Dina G. Tiniakos
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  9. Μichael N. Alexis
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Correspondence to Μichael N. Alexis.

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Νiki Ι. Chantzi and Dina G. Tiniakos contributed equally to this work and share first authorship.

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Chantzi, Ν.Ι., Tiniakos, D.G., Palaiologou, M. et al. Estrogen receptor beta 2 is associated with poor prognosis in estrogen receptor alpha-negative breast carcinoma. J Cancer Res Clin Oncol 139, 1489–1498 (2013). https://doi.org/10.1007/s00432-013-1467-4

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  • DOI: https://doi.org/10.1007/s00432-013-1467-4

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