Association of aromatase with bladder cancer stage and long-term survival: new insights into the hormonal paradigm in bladder cancer

Nguyen, Daniel P. and O'Malley, Padraic and Al Hussein Al Awamlh, Bashir and Furrer, Marc-Alain and Mongan, Nigel P. and Robinson, Brian D. and Wang, Gerald J. and Scherr, Douglas S. (2016) Association of aromatase with bladder cancer stage and long-term survival: new insights into the hormonal paradigm in bladder cancer. Clinical Genitourinary Cancer . ISSN 1938-0682 (In Press)

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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.

Item Type: Article
Keywords: Estrogen receptor beta; Hormones; Regulation; Stage; Tumor marker
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Identification Number: https://doi.org/10.1016/j.clgc.2016.05.017
Depositing User: Mongan, Nigel
Date Deposited: 10 Oct 2016 14:27
Last Modified: 10 Oct 2016 20:59
URI: http://eprints.nottingham.ac.uk/id/eprint/36659

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