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. 2016 Apr 7:6:24263.
doi: 10.1038/srep24263.

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

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

Hao Lun Luo et al. Sci Rep. .

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 (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 effects were examined by multivariate analysis. This study divided patients into either the ERβ-high (n = 52) or ERβ-low (n = 53) group and analyzed their oncologic outcomes. All pathological features except infiltrating tumor architecture (significantly higher incidence in ERβ-low group, p = 0.004) are symmetric in both groups. Low ERβ 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 ERβ cause less UTUC proliferation and migration. In addition, ERβ agonist also enhanced the cytotoxic and migration inhibition effect of cisplatin and ERβ 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.

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Figures

Figure 1
Figure 1
(a) 40X microscopic view of high ERβ expression specimen. (b) 100X microscopic view of high ERβ expression specimen.
Figure 2
Figure 2
(a) ERβ effect on local recurrence free survival for pT3 UT-UC. (b) ERβ effect on distant metastasis free survival for pT3 UT-UC.
Figure 3
Figure 3. Wound healing assay revealed ERβ knock down UTUC cells were more proliferative in 24 hours observation.
Figure 4
Figure 4. Migration assay revealed ERβ knock down UTUC cells were tend to more aggressive.
Figure 5
Figure 5
(a) The microscopic view for migration assessment of UTUC cell line by different combination of cisplatin, PHTPP, and DPN. (b) Cisplatin can cause less migration of UTUC cells. PHTPP causes UTUC cells more resistant to cisplatin treatment and DPN enhances the cisplatin effect.

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