Prognostic Significance of Estrogen Receptor Expression in Superficial Transitional Cell Carcinoma of the Urinary Bladder

Basakci, Alper; Kirkali, Ziya; Tüzel, Emre; Yörükoğlu, Kutsal; Mungan, Mehmet Uğur; Sade, Murat

doi:10.1016/s0302-2838(02)00038-6

Cited by 33 publications

(30 citation statements)

References 11 publications

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“…In our study, ER ␤ expression was significantly lower in poorly differentiated cells, and this progressive decline was correlated with the loss of cancer cell proliferation, suggesting a protective role of ER ␤ during progression of bladder cancer. This finding is inconsistent with previous data on human bladder cancer, suggesting tumorigenic potential of ERs [13,14] , or no direct impact on patients' prognosis [15] . Discordant results among studies may be explained by the presence of distinct ER ␤ isoforms with opposing effects on target genes resulting in diverse clinical outcomes.…”

Section: Discussioncontrasting

confidence: 99%

Expression of ERβ and Its Co-Regulators p300 and NCoR in Human Transitional Cell Bladder Cancer

Kontos¹,

Papatsoris

Kominea³

et al. 2011

Urol Int

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Objective: Several data support a possible role of estrogens in bladder carcinogenesis, mediated mainly through estrogen receptor-β (ERβ). We study the expression of ERβ and its co-regulators p300 and nuclear co-repressor (NCoR) in patients with bladder cancer. Patients and Methods: One hundred and eleven consecutive patients (74 males and 37 females), aged 23–90 years (mean 70 ± 10) diagnosed with transitional cell bladder cancer were included in this study. The control group consisted of 29 patients that underwent transurethral prostatectomy and consented to simultaneous bladder biopsies. Immunohistochemical studies took place on formalin-fixed, paraffin-embedded sections from the TUR (transurethral resection) specimens. We studied the expression of ERβ, p300 and NCoR.χ² test was used to evaluate the relationship between the histological grade and ERβ expression, grade and co-regulators expression and grade and gender. Spearman rank correlation coefficient (r) was used in order to estimate the direction and strength of correlations between histological grade and ERβ-p300-NCoR expressions. The Cochran-Armitage test for trend was applied in order to examine possible trends across the ordered levels of histological grade. Results: ERβ was more frequently expressed in the nucleus of normal bladder epithelium compared to malignant bladder epithelium with statistical significant association (r = –0.25, p = 0.003). The p300 was expressed only in the nucleus of bladder cancer cells and a positive correlation between molecular expression and cancer progression was demonstrated (r = 0.55, p < 0.001). NCoR immunostaining was demonstrated in the nuclei of bladder cells. Nuclear staining was significantly higher in normal tissue than in cancer cells (r = –0.33, p < 0.001), with negative correlation. Furthermore, its expression in grade I tumors was significantly higher than in grade II (r = –0.46, p < 0.001) and grade III tumors (r = –0.51, p < 0.001). Thus, like ERβ, NCoR expression in bladder epithelium decreased during cancer progression and loss of cell differentiation. There was no correlation between the levels of expression of the three proteins in normal bladder epithelium, but there was an inverse correlation between the nuclear expression of ERβ and p300 in carcinomas (r = –3.88, p = 0.042). Statistical significant association was established when correlating ERβ expression with NCoR expression (r = 0.273, p = 0.005), while co-regulators’ nuclear expression did not correlate with each other (p > 0.05). Conclusions: In bladder carcinogenesis, we demonstrated inhibition in the expression of ERβ and its co-repressor NCoR as well as increased expression of the co-activator p300.

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Section: Discussioncontrasting

confidence: 99%

Expression of ERβ and Its Co-Regulators p300 and NCoR in Human Transitional Cell Bladder Cancer

Kontos¹,

Papatsoris

Kominea³

et al. 2011

Urol Int

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“…[11][12][13] In superficial bladder cancer, ER-b expression is 12% compared with 70% in MIBC. 17 In a study by Shen et al, 11 ER-b expression was detected in 63% of the bladder tumors (58% and 70% of World Health Organization grade 1/2 and grade 3 tumors, respectively; P ¼ .085). 11 The investigators reported a correlation between the degree of ER-b expression and the increasing disease stage, with a statistically significant difference between Ta/T1 and T2/T3/T4 tumor ER-b expression (P < .001).…”

Section: Discussionmentioning

confidence: 96%

“…However, these results are not consistent across different studies, and the discrepancies in part may be due to differences in study design, tissue collection, staining methods, and criteria for determining assay positivity. 4,17,18 The objective of our study was to evaluate the incidence of ER-a and ER-b expression in patients with bladder cancer who were treated with cystectomy at the Mayo Clinic for whom validated clinical data were available.…”

Section: Introductionmentioning

confidence: 99%

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

Tan

Boorjian

Advani

et al. 2015

Clinical Genitourinary Cancer

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“…The role of ERα as a positive regulator of proliferation and its association with inflammatory responses and the development of malignancy are well established [41]. Nonetheless, the importance of ERα to urothelial cancer in humans is unclear with most studies reporting little expression of the receptor, although a recent report linked a loss of ERα expression with higher grade tumors [20,[32][33][34][35][36]38,65]. Future studies with BBN exposure of mice with a urothelial-specific knockout of ERα should be able to address potential roles of ERα in carcinogen-induced tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

“…In human bladder cancer, most reports indicate a low percentage of tumors expressing ERα [32][33][34][35][36] with several studies failing to detect any ERα expression [37,38]. A recent report indicated weak expression of ERα in 27% of primary bladder cancer tissues, with no correlation between ERα and tumor recurrence, progression, or cancer-specific survival [20].…”

Section: Introductionmentioning

confidence: 99%

Chemoprevention of BBN-Induced Bladder Carcinogenesis by the Selective Estrogen Receptor Modulator Tamoxifen

George¹,

Tovar-Sepulveda²,

Shen³

et al. 2011

CLINICAL/TRANSLATIONAL - Endocrine Neoplasia

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Bladder cancer is the fifth most frequent tumor in men and ninth in women in the United States. Due to a high likelihood of recurrence, effective chemoprevention is a significant unmet need. Estrogen receptors (ERs), primarily ERβ, are expressed in normal urothelium and urothelial carcinoma, and blocking ER function with selective ER modulators such as tamoxifen inhibits bladder cancer cell proliferation in vitro. Herein, the chemoprotective potential of tamoxifen was evaluated in female mice exposed to the bladder-specific carcinogen, N -butyl-N -(4-hydroxybutyl) nitrosamine (BBN). Carcinogen treatment resulted in a 76% tumor incidence and increased mean bladder weights in comparison to controls. In contrast, mice receiving tamoxifen concurrent (8-20 weeks) or concurrent and subsequent (8-32 weeks) to BBN administration had no change in bladder weight and only 10% to 14% incidence of tumors. Non-muscle-invasive disease was present in animals treated with tamoxifen before (5-8 weeks) or after (20-32 weeks) BBN exposure, while incidence of muscle-invasive bladder carcinoma was reduced. ERβ was present in all mice and thus is a potential mediator of the tamoxifen chemoprotective effect. Surprisingly, ERα expression, which was detected in 74% of the mice exposed to BBN alone but not in any control mice, was correlated with tumor incidence, indicating a possible role for this receptor in carcinogen-induced urothelial tumorigenesis. Thus, these data argue that both ERα and ERβ play a role in modulating carcinogen-induced bladder tumorigenesis. Administration of tamoxifen should be tested as a chemopreventive strategy for patients at high risk for bladder cancer recurrence.Translational Oncology (2013) 6, 244-255 IntroductionAs the fifth most common cancer in men and ninth most common in women in the United States, urinary bladder cancer accounts for significant morbidity and mortality. There are estimated to be more than 73,000 new bladder cancer cases in 2012 [1] with urothelial carcinoma accounting for approximately 90% of these; the remainder is composed of squamous cell carcinomas, adenocarcinomas, and other rare histologies [2]. Approximately 70% of all new bladder cancer cases are classified as non-muscle-invasive (Ta, T1, Tis), while the remaining 30% are muscle-invasive (T2-T4) and generally lead to cystectomy. Bladder cancer recurs at a very high rate of 50% to 90% depending on the tumor stage, grade, and number of primary tumors, and this necessitates lifetime monitoring for tumor recur-

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Prognostic Significance of Estrogen Receptor Expression in Superficial Transitional Cell Carcinoma of the Urinary Bladder

Cited by 33 publications

References 11 publications

Expression of ERβ and Its Co-Regulators p300 and NCoR in Human Transitional Cell Bladder Cancer

Expression of ERβ and Its Co-Regulators p300 and NCoR in Human Transitional Cell Bladder Cancer

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

Chemoprevention of BBN-Induced Bladder Carcinogenesis by the Selective Estrogen Receptor Modulator Tamoxifen

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