The Estrogen Pathway: Estrogen Receptor-α, Progesterone Receptor, and Estrogen Receptor-β Expression in Radical Cystectomy Urothelial Cell Carcinoma Specimens

The estrogen pathway has been implicated in bladder cancer growth and progression. We evaluated the expression and intensity of estrogen receptor (ER)-α, ER-β, and progesterone receptor in patients with urothelial cell carcinoma who were treated with cystectomy. Progesterone receptor expression was negative in all cases. ER-α expression was noted in 12 of 318 patients, and ER-β expression was noted in all patients. Marked ER-β intensity was associated with decreased lymph node metastasis, smaller tumor size, preoperative Bacillus Calmettee - Guérin, and less nonorgan-confined disease, suggesting a potential prognostic role of ER-β in urothelial cell carcinoma. Objective: Bladder cancer has the sixth highest incidence in the United States. Treatment of metastatic bladder cancer is difficult, and mortality is certain. There are certain pathways in cancer growth and progression that are important in bladder cancer development. Recently, the estrogen pathway has been found to be a potential target for therapy. Methods: We identified 410 patients treated with radical cystectomy for urothelial cell carcinoma between 1990 and 1994. We obtained representative paraffin-embedded tissue blocks for 336 (82.0%) of these cases and evaluated the expression and intensity of estrogen receptor (ER)-α, ER-β, and progesterone receptor by immunohistochemistry. Results: Among the 12 ER-α-positive cases, median tumor ER-α expression was 10% (range, 10%-50%). In contrast to ER-α, all cases were ER-β-positive. Median tumor ER-β expression was 90% (range, 20%-100%). Nearly all cases had ER-β expression of ≥ 90% (175 [55.9%] with 90% and 103 [32.9%] with 100%). However, the intensity of ER-β staining varied from focal to moderate to marked in 64 (20.5%), 167 (53.4%), and 82 (26.2%) cases, respectively. Progesterone receptor expression was noted to be negative in all cases. Conclusions: ER-β is highly expressed in bladder cancer. Prospective validation of these data might further elucidate the utility of ER-β as a marker for prognosis or possible target for therapy.