Eltze, Elke and Wild, Peter J. and Wuelfing, Christian and Zwarthoff, Ellen C. and Burger, Maximilian and Stoehr, Robert and Korsching, Eberhard and Hartmann, Arndt (2009) Expression of the Endothelin Axis in Noninvasive and Superficially Invasive Bladder Cancer: Relation to Clinicopathologic and Molecular Prognostic Parameters. EUROPEAN UROLOGY, 56 (5). pp. 837-845. ISSN 0302-2838, 1873-7560
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Background: The endothelin (ET) axis plays a role in cancer biology and plays a potential role as a target for molecular therapy in urogenital tumours. Alterations of several proteins of the ET axis were detected in invasive bladder cancer. Objectives: To examine the potential role of the expression of ET axis proteins compared to other prognostic parameters (kinase inhibitor 67 [Ki-67], tumour protein 53 [TP53], and fibroblast growth factor receptor 3 gene [FGFR3] mutations) in noninvasive and invasive bladder cancer. Design, setting, and participants: Tissue microarrays from 154 consecutive patients with pTa-pT2 urothelial bladder cancer were immunohistochemically stained for endothelin 1 (ET-1), endothelin A and B receptors (ETAR, ETBR), TP53, and Ki-67. FGFR3 mutations were detected by SNaPshot analysis. Measurements: The results were correlated with clinicopathologic parameters and disease-specific survival, overall survival, and recurrence-free survival. Results and limitations: Proteins of the ET axis were frequently expressed in bladder cancer (ET-1 in 62% of tumours, ETAR in 93% of tumours, and ETBR in 84% of tumours). ET-1 expression was strongly correlated with tumour stage (p = 0.015), histologic grade (p = 0.008), and low proliferation status ( p = 0.003). ETAR immunostaining was only associated with low proliferation status (p = 0.015). Kaplan-Meier survival analysis showed a significantly longer overall survival for patients with ET-1-expressing tumours (p = 0.007). A significantly longer disease-free survival was found in patients with ETAR-expressing tumours (p = 0.040), whereas ETBR expression was significantly correlated to a longer disease-free survival only in subgroups of patients with multifocal tumours (p = 0.031), low proliferation index (Ki-67 <= 10; p = 0.050), low TP53 expression (<= 10; p = 0.018), and tumours with an FGFR3 mutation (p = 0.026). In the global model for recurrence-free survival, only high-grade (p = 0.048) and negative ETAR immunoreactivity (p = 0.048) were correlated with poor prognosis. Conclusions: In addition to other factors, particularly age at diagnosis and growth pattern, lack of ET-1 expression may be an independent negative prognostic factor for the overall-survival probability of bladder cancer patients. Lack of ETAR expression may be an independent negative marker for recurrence-free survival. (C) 2008 European Association of Urology. Published by Elsevier B. V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | UROTHELIAL CELL-CARCINOMA; ATTENUATES APOPTOSIS; FGFR3 MUTATIONS; B RECEPTORS; GRADE; TUMORS; PROLIFERATION; PROGRESSION; NEOPLASMS; PROSTATE; Endothelin axis; Endothelin receptors; Superficial bladder cancer; Prognostic factor |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Sep 2020 08:39 |
| Last Modified: | 02 Sep 2020 08:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28184 |
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