Expression of Androgen and Estrogen Receptors and Its Prognostic Significance in Urothelial Neoplasm of the Urinary Bladder
Hiroshi Miyamoto, Jorge L Yao, Alcides Chaux, Qi Yang, Loralee A McMahon, Yichun Zheng, Koji Izumi, George J Netto. University of Rochester, Rochester, NY; Johns Hopkins Medical Institution, Baltimore, MD
Background: Men have a significantly higher risk of bladder cancer than women, whereas female patients have been shown to present with less favorable tumor characteristics than male patients. Steroid hormone receptor signals have been implicated in bladder carcinogenesis and cancer progression. Although there are several reports showing the expression of androgen receptor (AR) and estrogen receptors (ERs) in bladder cancer, recent studies have demonstrated conflicting results and the prognostic significance remains unclear.
Design: We investigated the expression of AR, ERα, and ERβ in 188 bladder tumor specimens, as well as matched 141 non-neoplastic bladder and 14 lymph node metastasis tissues, by immunohistochemistry. We then evaluated the relationships between their expression and clinicopathologic features available for our patient cohort.
Results: AR/ERα/ERβ was positive in 80%/50%/89% of benign urothelium, 50%/67%/41% of benign stroma, 42%/27%/49% of primary tumors, and 71%/64%/71% of metastatic tumors. Significantly lower expressions of AR/ERα were found in high-grade (36%/23%) and muscle-invasive (33%/19%) tumors than in low-grade (55%; P=0.0232/38%; P=0.0483) and non-muscle-invasive (51%; P=0.0181/35%; P=0.0139) tumors, respectively. Significantly higher expressions of ERβ were found in high-grade (58%) and muscle-invasive (67%) tumors than in low-grade (29%; P=0.0002) and non-muscle-invasive (34%; P<0.0001) tumors, respectively. There was no significant difference in expression pattern of each receptor between bladder tumors from male versus female patients. Additionally, there was a statistically significant inverse relationship between ERα expression and ERβ expression in bladder cancer (P=0.0216), whereas no significant correlations between expressions of AR and ERα or ERβ were seen. Kaplan-Meier and log-rank tests further revealed that positivity of ERβ, but not AR or ERα, was associated with recurrence of low-grade tumor (P=0.0072), progression of low-grade tumor (P=0.0005), non-muscle-invasive high-grade tumor (P=0.0020), and muscle-invasive tumor (P=0.0010), or disease-specific mortality in patients with muscle-invasive tumor (P=0.0073).
Conclusions: Compared to benign bladders, significant decreases in the expression of AR, ERα, or ERβ in bladder cancer were seen. Loss of AR or ERα was strongly associated with higher grade/more invasive tumors, while ERβ expression was increased in high-grade/invasive tumors and predicted worse prognosis.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 137, Wednesday Afternoon