Vinayagam, Raman; Sibson, D. Ross; Holcombe, Christopher; Aachi, Vijay and Davies, Michael P.A. (2007) Association of oestrogen receptor beta 2 (ERβ2/ERβcx) with outcome of adjuvant endocrine treatment for primary breast cancer – a retrospective study. BMC Cancer, 7 . Article Number: 131. ISSN 1471-2407
Available under License Creative Commons Attribution.
Background: Oestrogen receptor beta (ERβ) modulates ERα activity; wild type ERβ (ERβ1) and its splice variants may therefore impact on hormone responsiveness of breast cancer. ERβ2/ERβcx acts as a dominant negative inhibitor of ERα and expression of ERβ2 mRNA has been proposed as a candidate marker for outcome in primary breast cancer following adjuvant endocrine therapy. We therefore now assess ERβ2 protein by immunostaining and mRNA by quantitative RT-PCR in relation to treatment outcome. Methods: ERβ2-specific immunostaining was quantified in 141 primary breast cancer cases receiving adjuvant endocrine therapy, but no neoadjuvant therapy or adjuvant chemotherapy. The expression of mRNA for ERβ2/ ERβcx was measured in 100 cases by quantitative RT-PCR. Statistical analysis of breast cancer relapse and breast cancer survival was performed using Kaplan Meier log-rank tests and Cox's univariate and multivariate survival analysis. Results: High ERβ2 immunostaining (Allred score >5) and high ERβ2 mRNA levels were independently associated with significantly better outcome across the whole cohort, including both ERα positive and negative cases (Log-Rank P < 0.05). However, only ERβ2 mRNA levels were significantly associated with better outcome in the ERα + subgroup (Log-Rank P = 0.01) and this was independent of grade, size, nodal status and progesterone receptor status (Cox hazard ratio 0.31 P = 0.02 for relapse; 0.17 P = 0.01 for survival). High ERβ2 mRNA was also associated with better outcome in node negative cases (Log Rank P < 0.001). ERβ2 protein levels were greater in ERα positive cases (T-test P = 0.00001), possibly explaining the association with better outcome. Levels of ERβ2 protein did not correlate ERβ2 mRNA levels, but 34% of cases had both high mRNA and protein and had a significantly better outcome (Log-Rank relapse P < 0.005). Conclusion: High ERβ2 protein levels were associated with ERα expression. Although most cases with high ERβ2 mRNA had strong ERβ2 immunostaining, mRNA levels but not protein levels were independently predictive of outcome in tamoxifen-treated ERα + tumours. Post-transcriptional control needs to be considered when assessing the biological or clinical importance of ERβ proteins.
|Additional Information:||9 pages (page numbers not for citation purposes). Published: 18 July 2007.|
|Uncontrolled Keywords:||ER-BETA; MESSENGER-RNA; TAMOXIFEN; THERAPY; EXPRESSION; ER-BETA-1; CX; RESISTANCE; VARIANTS; SURVIVAL|
|Subjects:||R Medicine > R Medicine (General)|
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
|Departments, Research Centres and Related Units:||Academic Faculties, Institutes and Research Centres > Faculty of Medicine > School of Cancer Studies|
|Publisher's Statement:||© 2007 Vinayagam et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.|
|Deposited On:||06 Jun 2008 11:22|
|Last Modified:||22 Mar 2012 11:55|
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