INVESTIGATIVE UROLOGY

Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer
Boorjian S, Ugras S, Mongan NP, Gudas LJ, You X, Tickoo SK, Scherr DS
Department of Urology, New York Presbyterian Hospital-Weill-Cornell Medical Center, New York, New York, USA
Urology. 2004; 64: 383-8

• Objectives: To evaluate the expression of the androgen receptor (AR) in transitional cell carcinoma (TCC) of the bladder, and to assess whether its expression correlated with pathologic tumor stage. TCC of the bladder is three times more common in males than in females. The origin of this sex difference in incidence is unknown.
• Methods: We evaluated tumor specimens from 49 consecutive patients treated for TCC of the bladder at our institution between July 2002 and June 2003. Immunohistochemistry was performed using a monoclonal mouse anti-AR antibody on paraffin-embedded tissue sections of tumors obtained from transurethral resection, radical cystectomy, or resection of metastases. Specimens were assessed for AR expression, and, in tumors that demonstrated AR staining, the percentage of nuclei that stained positive was recorded.
• Results: Of the 49 tumors, 26 (53.1%) expressed the AR. The percentage of tumors that expressed the AR decreased with increasing pathologic stage, from 88.9% of pTa lesions to 0% of pT3 tumors. Overall, 75% of superficial tumors (pTa + pT1 + carcinoma in situ) expressed the AR compared with 21.4% of invasive tumors (pT2 + pT3; P = 0.002). In addition, among AR-expressing tumors, the mean percentage of nuclei that stained positive for the AR was significantly greater in pTa tumors (62.5%) than in pT1 (31%) or pT2 (20%) tumors (P = 0.005).
• Conclusions: We found a decrease in AR protein expression in tumors with increased pathologic stage. Our data suggest that the loss of AR expression is associated with invasive bladder cancer.
  
  
• Editorial Comment
  A previous study that considered smoking and occupational risks showed that the sex-related risk of bladder cancer for men persists independently of other risks (1). Some experimental studies in rats showed that the bladder tumors development is significantly grater in males than in females (2,3), although studies in humans are still scarce. A functional role for the AR in human bladder cancer has been suggested by a recent study that demonstrated that androgen treatment inhibited bacille Calmette-Guérin-induced interleukin-6 expression in bladder cancer cell lines that expressed the AR. The study also demonstrated that pharmacologic androgen deprivation restored bacille Calmette-Guérin-induced interleukin-6 expression (4).
  In this present important contribution, Boorjian et al., after evaluating 49 tumor specimens, found a decrease in androgen receptors correspondent to increased pathologic stage. The authors suggest that as a potential therapeutic application, given the high percentage of superficial (particularly Ta) tumors that expressed the AR in the present study, together with the results of androgen deprivation therapy in animal studies, the potential exists to investigate the impact of androgen deprivation therapy in superficial bladder cancer.

References
1. Hartge P, Harvey EB, Linehan WM, Silverman DT, Sullivan JW, Hoover RN, et al.: Unexplained excess risk of bladder cancer in men. J Natl Cancer Inst. 1990; 82: 1636-40.
2. Boorman GA: Animal model of human disease: carcinoma of the ureter and urinary bladder. Am J Pathol. 1977; 88: 251-4.
3. Okajima E, Hiramatsu T, Iriya K, Ijuin M, Matsushima S: Effects of sex hormones on development of urinary bladder tumours in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. Urol Res. 1975; 3: 73-9.
4. Chen F, Langenstroer P, Zhang G, Iwamoto Y, See WA: Androgen dependent regulation of bacillus Calmette-Guérin induced interleukin-6 expression in human transitional carcinoma cell lines. J Urol. 2003; 170: 2009-13.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil