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Expression of Estrogen Receptor Beta Predicts Oncologic Outcome of pT3 Upper Urinary Tract Urothelial Carcinoma Better Than Aggressive Pathological Features.

ABSTRACT: Upper urinary tract urothelial carcinoma (UT-UC) is rare and treatment options or prognostic markers are limited. There is increasing evidence indicating that urothelial carcinoma may be an endocrine-related cancer. The aim of this study was to analyze the prognostic effect of estrogen receptor beta (ER?) on the outcome of UT-UC. From 2005 to 2012, this study included 105 patients with pT3 UT-UC. Perioperative factors, pathological features, and ER? immunostaining were reviewed and prognostic effects were examined by multivariate analysis. This study divided patients into either the ER?-high (n = 52) or ER?-low (n = 53) group and analyzed their oncologic outcomes. All pathological features except infiltrating tumor architecture (significantly higher incidence in ER?-low group, p = 0.004) are symmetric in both groups. Low ER? expression was significantly correlated with local recurrence and distant metastasis in univariate analysis (p = 0.035 and 0.004, respectively) and multivariate analysis (p = 0.05 and 0.008, respectively). Cell line study also proved that knock down of ER? cause less UTUC proliferation and migration. In addition, ER? agonist also enhanced the cytotoxic and migration inhibition effect of cisplatin and ER? antagonist cause the UTUC cell more resistant to cisplatin. This result may help identify patients in need of adjuvant therapy or develop potential targeted therapy.

SUBMITTER: Luo HL

PROVIDER: S-EPMC4823660 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Expression of Estrogen Receptor Beta Predicts Oncologic Outcome of pT3 Upper Urinary Tract Urothelial Carcinoma Better Than Aggressive Pathological Features.

Luo Hao Lun HL Sung Ming Tse MT Tsai Eing Mei EM Lin Chang Shen CS Lee Nai Lun NL Chung Yueh-Hua YH Chiang Po Hui PH

Scientific reports 20160407

Upper urinary tract urothelial carcinoma (UT-UC) is rare and treatment options or prognostic markers are limited. There is increasing evidence indicating that urothelial carcinoma may be an endocrine-related cancer. The aim of this study was to analyze the prognostic effect of estrogen receptor beta (ERβ) on the outcome of UT-UC. From 2005 to 2012, this study included 105 patients with pT3 UT-UC. Perioperative factors, pathological features, and ERβ immunostaining were reviewed and prognostic ef ...[more]

PMID: 27052470

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Project description:Cigarette smoking is a common risk factor for developing upper tract urothelial carcinoma (UTUC).To assess the impact of cigarette smoking status, cumulative smoking exposure, and time from cessation on oncologic UTUC outcomes in patients treated with radical nephroureterectomy (RNU).A total of 864 patients underwent RNU at five institutions. The median follow-up in this retrospective study was 50 mo. Smoking history included smoking status, quantity of cigarettes per day (CPD), duration in years, and years from smoking cessation. The cumulative smoking exposure was categorized as light-short-term (? 19 CPD and ? 19.9 yr), moderate (all combinations except light-short-term and heavy-long-term), and heavy-long-term (? 20 CPD and ? 20 yr).RNU with or without lymph node dissection. No patient received neoadjuvant chemotherapy.Univariable and multivariable logistic regression and competing risk regression analyses assessed the effects of smoking on oncologic outcomes.A total of 244 patients (28.2%) never smoked; 297 (34.4%) and 323 (37.4%) were former and current smokers, respectively. Among smokers, 87 (10.1%), 331 (38.3%), and 202 (23.4%) were light-short-term, moderate, and heavy-long-term smokers, respectively. Current smoking status, smoking ? 20 CPD, ? 20 yr, and heavy-long-term smoking were associated with advanced disease (p values ? 0.004), greater likelihood of disease recurrence (p values ? 0.01), and cancer-specific mortality (p values ? 0.05) on multivariable analyses that adjusted for standard features. Patients who quit smoking ? 10 yr prior to RNU did not differ from never smokers regarding advanced tumor stages, disease recurrence, and cancer-specific mortality, but they had better oncologic outcomes then current smokers and those patients who quit smoking <10 yr prior to RNU. The study is limited by its retrospective nature.Cigarette smoking is significantly associated with advanced disease stages, disease recurrence, and cancer-specific mortality in patients treated with RNU for UTUC. Current smokers and those with a heavy and long-term smoking exposure have the highest risk for poor oncologic outcomes. Smoking cessation >10 yr prior to RNU seems to mitigate some detrimental effects. These results underscore the need for smoking cessation and prevention programs.

Project description:BackgroundNumerous studies have investigated the risk factors of intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper urinary tract urothelial carcinoma (UTUC). However, few studies explore the predictors for unfavorable pathological types of IVR following RNU.MethodsWe retrospectively reviewed 155 patients diagnosed with bladder cancer (BC) following RNU. Binary logistic regression was used for the univariable and multivariable analyses. Nomograms were developed based on the multivariable analysis. The concordance index (C-index) was used to assess the performance of the nomograms. We performed internal validation by generating calibration plots.ResultsMuscle-invasive BC (MIBC) was significantly correlated with operation interval (p = 0.004) and UTUC T-stage (p = 0.016). Operation interval (p = 0.002) and UTUC T-stage (p = 0.028) were also risk factors for BC > 3 cm. UTUC grade (p = 0.015), operation interval (p = 0.003), and hydronephrosis (p = 0.049) were independent predictors for high-grade BC (HGBC). MIBC (p = 0.018) and surgical approach (p = 0.003) were associated with multifocal IVR. Besides, MIBC and HGBC were associated with UTUC grade (p = 0.009), operation interval (p = 0.001), and hydronephrosis (p = 0.023). Moreover, only operation interval (p = 0.036) was a predictor for BC with at least one unfavorable pathological type. We developed nomograms for MIBC, HGBC, BC > 3 cm, and MIBC and/or HGBC. The calibration curves of the nomograms showed good agreement between the observation and prediction cases. The C-indexes of the nomograms were 0.820 (95% CI, 0.747-0.894), 0.728 (95% CI, 0.649-0.809), 0.770 (95% CI, 0.679-0.861), and 0.749 (95% CI, 0.671-0.827), respectively.ConclusionsThe current study found that operation interval, UTUC T-stage, UTUC grade, surgical approach, and hydronephrosis are independent predictors for unfavorable pathological types of IVR following RNU. Nomograms based on these predictors were developed and internally validated to assess the risk of developing unfavorable pathological types of IVR. Furthermore, patients at high risk of developing unfavorable pathological types BC may benefit from more active follow-up 1 year after RNU by early detection of IVR.

Dataset Information

Expression of Estrogen Receptor Beta Predicts Oncologic Outcome of pT3 Upper Urinary Tract Urothelial Carcinoma Better Than Aggressive Pathological Features.

Publications

Expression of Estrogen Receptor Beta Predicts Oncologic Outcome of pT3 Upper Urinary Tract Urothelial Carcinoma Better Than Aggressive Pathological Features.

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