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Association of Aromatase With Bladder Cancer Stage and Long-Term Survival: New Insights Into the Hormonal Paradigm in Bladder Cancer

Nguyen, Daniel P.; O'Malley, Padraic; Al Hussein Al Awamlh, Bashir; Furrer, Marc-Alain; Mongan, Nigel P.; Robinson, Brian D.; Wang, Gerald J.; Scherr, Douglas S.

Authors

Daniel P. Nguyen

Padraic O'Malley

Bashir Al Hussein Al Awamlh

Marc-Alain Furrer

Brian D. Robinson

Gerald J. Wang

Douglas S. Scherr



Abstract

BACKGROUND

Hormonal factors may play a role in bladder cancer (BCa). We investigated the expression of aromatase and estrogen receptor (ER)β and its association with pathological variables and survival outcomes.

PATIENTS AND METHODS

BCa specimens from 40 patients were evaluated. Immunohistochemistry was performed for aromatase and ERβ. Descriptive statistics and univariate analyses assessed the association of these markers with pathologic variables and survival outcomes.

RESULTS

Aromatase expression was significantly associated with tumor stage; muscle-invasive disease was found in 15 of 19 (79%) patients with positive staining and in 7 of 18 (39%) patients with negative staining (P = .02). Node-positive disease was found in 8 of 19 (42%) patients with positive staining and 1 of 18 (6%) patients with negative staining (P = .01). After a median follow-up of 112 months, Cox regression analysis demonstrated that aromatase expression was associated with a more than 2-fold risk of cancer recurrence (hazard ratio, 2.37; confidence interval, 0.92-6.08; P = .07) and an almost 4-fold higher risk of cancer-specific death (hazard ratio, 3.66; 95% confidence interval, 1.19-12.06; P = .02). Muscle-invasive disease was found in 15 of 18 (83%) ERβ-positive specimens and 4 of 12 (33%) ERβ-negative specimens (P = .0009). Hierarchical clustering analysis demonstrated a 4-fold up-regulation of ERβ gene expression in tumor versus adjacent, non-tumor urothelium (P < .05). However, no significant association with survival outcomes was found.

CONCLUSION

Aromatase expression in BCa may be associated with advanced tumor stage and poorer survival outcomes. ERβ is upregulated in malignant tissue, and its expression is associated with muscle-invasive disease. These findings provide further evidence for the hormonal paradigm in BCa.

Citation

Nguyen, D. P., O'Malley, P., Al Hussein Al Awamlh, B., Furrer, M., Mongan, N. P., Robinson, B. D., …Scherr, D. S. (2017). Association of Aromatase With Bladder Cancer Stage and Long-Term Survival: New Insights Into the Hormonal Paradigm in Bladder Cancer. Clinical Genitourinary Cancer, 15(2), 256-262.e1. https://doi.org/10.1016/j.clgc.2016.05.017

Journal Article Type Article
Acceptance Date May 21, 2016
Online Publication Date May 27, 2016
Publication Date 2017-04
Deposit Date Oct 10, 2016
Publicly Available Date Oct 10, 2016
Journal Clinical Genitourinary Cancer
Print ISSN 1558-7673
Electronic ISSN 1938-0682
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 15
Issue 2
Pages 256-262.e1
DOI https://doi.org/10.1016/j.clgc.2016.05.017
Keywords Estrogen receptor beta; Hormones; Regulation; Stage; Tumor marker
Public URL http://eprints.nottingham.ac.uk/id/eprint/36659
Publisher URL http://www.sciencedirect.com/science/article/pii/S1558767316301434
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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