Portal de Periódicos da CAPES

159 ASSOCIATION OF ANGIOGENESIS-RELATED MARKERS WITH BLADDER CANCER OUTCOMES AND OTHER MOLECULAR MARKERS

2010; Lippincott Williams & Wilkins; Volume: 183; Issue: 4S Linguagem: Inglês

10.1016/j.juro.2010.02.213

1527-3792

Shahrokh F. Shariat, Ramy F. Youssef, Daher C. Chade, Pierre I. Karakiewicz, Hendrik Isbarn, Claudio Jeldres, Arthur I. Sagalowsky, Raheela Ashfaq, Yair Lotan,

Cancer, Lipids, and Metabolism

You have accessJournal of UrologyUrothelial Cancer: Natural History & Pathophysiology/Markers1 Apr 2010159 ASSOCIATION OF ANGIOGENESIS-RELATED MARKERS WITH BLADDER CANCER OUTCOMES AND OTHER MOLECULAR MARKERS Shahrokh Shariat, Ramy Youssef, Daher Chade, Pierre Karakiewicz, Hendrik Isbarn, Claudio Jeldres, Arthur Sagalowsky, Raheela Ashfaq, and Yair Lotan Shahrokh ShariatShahrokh Shariat Dallas, TX More articles by this author , Ramy YoussefRamy Youssef Dallas, TX More articles by this author , Daher ChadeDaher Chade Dallas, TX More articles by this author , Pierre KarakiewiczPierre Karakiewicz Montreal, Canada More articles by this author , Hendrik IsbarnHendrik Isbarn Montreal, Canada More articles by this author , Claudio JeldresClaudio Jeldres Montreal, Canada More articles by this author , Arthur SagalowskyArthur Sagalowsky Dallas, TX More articles by this author , Raheela AshfaqRaheela Ashfaq Dallas, TX More articles by this author , and Yair LotanYair Lotan Dallas, TX More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.213AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Angiogenesis is important for tumor growth and metastasis. Angiogenesis contributes to the tumor-promoting extracellular milieu by providing oxygen, nutrients, and growth factors to the neoplastic cells. Development of reliable molecular predictive markers is expected to improve treatment decisions, therapy development and outcomes in urothelial carcinoma of the bladder (UCB). Smaller studies have shown that vascular endothelial growth factor (VEGF), fibroblast growth factor (BFGF), thrombospondin 1 (TSP-1) levels and microvessel density (MVD-CD31) have prognostic value in UCB. To validate and further test the association of VEGF, BFGF, and TSP-1 expression as well as MVD with UCB characteristics and outcomes, we stained specimens from patients treated with radical cystectomy (RC). Moreover, we evaluated association of these angiogenesis-related markers with cell cycle-, proliferation-, and apoptosis-related molecular markers. METHODS VEGF, BFGF, TSP-I, MVD-CD31 immunohistochemical staining was performed on specimens from 204 patients treated with radical cystectomy for UCB. We also stained serial sections of the specimens for Cyclin E1, Cyclin D1, p53, p21, p27, pRB, Ki-67, Bcl-2, Caspase-3, Survivin, and cyclooxygenase-2. RESULTS The altered expression of VEGF (overexpression), BFGF (overexpression) and TSP-I (decreased expression) was 86%, 79% and 63%, respectively. Median MVD was 20. All four markers were associated with established clinicopathologic features of aggressive UCB (such as stage, lymphovascular invasion, and lymph node metastasis) and other molecular markers. In multivariable analyses that adjusted for standard pathologic features, BFGF and TSP-I were independent predictors of disease recurrence (HR 3.6, p=0.002 and HR=2.2, p=0.001, respectively) and cancer specific mortality (HR 2.8, p=0.02 and HR=2.3, p=0.003, respectively). When all four markers were included in one model, BFGF and TSP-1 retained their independent association with disease recurrence (HR=2.9, p=0.014 and HR=1.8, p=0.022, respectively) and only TSP-1 was independently associated with cancer-specific mortality (HR=1.9, p=0.031). CONCLUSIONS Angiogenesis-related molecular markers are commonly altered in UCB making them a target for therapy. Downregulation of TSP-I and up-regulation of BFGF are independent predictors of clinical outcomes of patients with UCB. © 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e64-e65 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shahrokh Shariat Dallas, TX More articles by this author Ramy Youssef Dallas, TX More articles by this author Daher Chade Dallas, TX More articles by this author Pierre Karakiewicz Montreal, Canada More articles by this author Hendrik Isbarn Montreal, Canada More articles by this author Claudio Jeldres Montreal, Canada More articles by this author Arthur Sagalowsky Dallas, TX More articles by this author Raheela Ashfaq Dallas, TX More articles by this author Yair Lotan Dallas, TX More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...