Daniel P. Nguyen
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
Padraic O'Malley
Bashir Al Hussein Al Awamlh
Marc-Alain Furrer
NIGEL MONGAN nigel.mongan@nottingham.ac.uk
Professor of Oncology
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.-A., 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 | https://nottingham-repository.worktribe.com/output/788383 |
Publisher URL | http://www.sciencedirect.com/science/article/pii/S1558767316301434 |
Contract Date | Oct 10, 2016 |
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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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