Original article Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: A comparative analysis of clinicopathological features and survival outcomes according to receptor expression Can Tuygun, M.D. a, *, Duygu Kankaya, M.D. b , Abdurrahim Imamoglu, M.D. a , Ayse Sertcelik, M.D. b , Kursad Zengin, M.D. a , Murat Oktay, M.D. c , Nurettin Sertcelik, M.D. a a Department of Urology, Ministry of Health Yildirim Beyazit Diskapi Educational and Research Hospital, Ankara, Turkey b Department of Pathology, Ankara University School of Medicine, Ankara, Turkey c Department of Pathology, Ministry of Health, Yildirim Beyazit Diskapi Educational and Research Hospital, Ankara, Turkey Received 25 November 2008; received in revised form 25 January 2009; accepted 27 January 2009 Abstract Objectives: To investigate the expression of sex-specific hormone receptors in normal bladder urothelium and urothelial carcinomas (UCs) of the bladder, and to analyze clinicopathological features and survival outcomes according to receptor expression. Methods: We evaluated the clinical data and tumor specimens of 139 patients with bladder cancer (BC). In addition, 72 samples of normal urothelium were included. Immunohistochemistry was performed using streptavidin-biotin peroxidase method, a monoclonal androgen receptor (AR), and an estrogen receptor- (ER) antibody on paraffin-embedded tissue sections. Expression levels of each receptor were assessed by evaluating 500 tumor cells for each case and the percentage of positively-stained nuclei was recorded. Results: None of the 58 male control cases showed any AR and ER expression. Five (35, 71%) of the 14 female control cases expressed ER. Of the 139 patients with UCs, 71 (51, 07%) expressed AR (62 male vs. 9 female; P = 0.413) and 44 (31, 65%) (39 male vs. 5 female; P = 0.402) showed ER expression (P  0.001). No significant relationship was found between ER expression levels and tumor grades, and stages (P = 0.441; P = 0.247). AR expression was significantly lower in T2-tumors (21%) than in Ta-tumors (60%) and T1-tumors (60%) (P  0.001). It was significantly higher in low-grade papillary UCs (64%) compared with high-grade papillary UCs (44%) and infiltrative high-grade UCs (17%) (P = 0.039; P  0.001). Data of 79 patients with noninvasive BC were eligible to present, with a median 29 months follow-up. AR expression level did not influence recurrence-free survival (RFS) and progression-free survival (PFS) (P = 0.095; P = 0.110). No significant association was found between ER expression level and RFS (P = 0.293). PFS in patients with lower ER-expressing tumors was significantly better than that in patients with higher ER-expressing tumors (P = 0.035). Multivariate analysis confirmed this significant influence on PFS (P = 0.025). Conclusions: Although ER expression had no impact on histopathological tumor characteristics, decrease in its expression may be associated with better PFS rates in patients with noninvasive BC. Conversely, loss of AR expression was associated with higher grade UCs and invasive UCs, but had no prognostic effect on survival. Finally, sex-specific hormone receptors alone cannot be responsible for gender differences in BC rates because they were expressed in similar rates in both sexes. © 2011 Elsevier Inc. All rights reserved. Keywords: Bladder cancer; Androgen receptor; Estrogen receptor; Immunohistochemistry; Prognosis 1. Introduction Bladder cancer (BC) is three times more common in men than in women, and tobacco smoking and also chemical exposures are the greatest environmental risk factors for the development of the difference in this gender incidence [1]. The roles of other risk factors, such as potential sex differ- ences in genetic, anatomic, and hormonal factors on the development of the difference in the BC rates between men and women have remained uncertain [2]. It is possible that sex steroid hormones have more responsibility than other factors in creating this difference. Data from an animal study demonstrates that androgen may have an effect on bladder carcinogenesis [3]. Other data from an epidemi- * Corresponding author. Tel.: +90-312-418-2878; fax: +90-312-424- 0040. E-mail address: tuyguncan@yahoo.com (C. Tuygun). Urologic Oncology: Seminars and Original Investigations 29 (2011) 43–51 1078-1439/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.urolonc.2009.01.033