Urothelial carcinoma of the bladder is nearly three times more common in men than in women. Although it has been primarily attributed to differences in exposure to smoking and industrial chemicals, it is evident now that hormonal factors also play a role. One of the explanations for the differential biologic aggressiveness of urothelial carcinoma of the bladder between genders has focused on sex steroid hormones and their receptors. Recent studies indicated that both estrogen receptor β and androgen receptor have a role within urothelial carcinoma of the bladder and their expression and activity are altered in the carcinogenesis and progression. Moreover, expression of transforming growth factor-β1 is a strong predictor of recurrence and specific mortality. We conjecture about the potential cross-talk between transforming growth factor-β1 and estrogen receptor β/androgen receptor pathways. Clinical significance of expression of transforming growth factor-β1 could be improved, when they are related with the determination of estrogen receptor β/androgen receptor status. Further subgrouping of transforming growth factor-β1 level combined with estrogen receptor β/androgen receptor status, would be more accurately determine the prognosis of patients. This hypothesis could be easily verified in corresponding clinical research, and combined analysis of expression of TGF-β1 and ERβ/AR signaling proteins may provide clinicians useful information regarding tumor initiation and progression, and guide patient prognosis and management with specific therapies.
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