title: Endothelin-1 overexpression: a potential biomarker of unfavorable prognosis in non-metastatic muscle-invasive bladder cancer.
abstract: Endothelin-1 (ET-1) is a multifunctional peptide exerting its effects via receptors A and B. ET-1 and its receptors, endothelin axis (ET axis), play a promoting role in cancer biology. Alterations of proteins of ET axis have been detected in non-metastatic muscle-invasive bladder cancer (NMMIBC). The objective of this study is to investigate the potential role of ET-1 tumor expression as a biomarker of prognosis, compared to other prognostic parameters (epidemiologic and pathologic), in NMMIBC. We prospectively included 40 consecutive, primary, high-grade NMMIBC patients. Tumor specimens after initial transurethral resection were stained immunohistochemically for ET-1. The ET-1 evaluation of expression was based on staining intensity (SI) of ET-1. SI was classified according to an arbitrary four-tiered scale (negative = 0, mild = 1, moderate = 2, strong = 3). Epidemiologic and pathologic parameters were analyzed, using univariate and multivariate statistics, for disease progression, progression-free survival (PFS), and overall survival (OS). ET-1 overexpression (SI = 3) was the unique parameter which associated significantly, both in univariate (log-rank test, p = 0.033) and multivariate (Cox regression analysis, p = 0.045, HR = 4.849, 95 % CI: 1.039-22.624) analysis, with an increased hazard ratio of progression. ET-1 overexpression (SI = 3) was also the unique parameter which associated, marginally significantly in univariate analysis (log-rank test, p = 0.056) and highly significantly in multivariate analysis (Cox regression analysis, p = 0.005, HR = 7.001, 95 % CI: 1.782-27.501), with an increased hazard ratio of death. Overexpression of ET-1 may be a potential biomarker of unfavorable prognosis in NMMIBC patients.
authors: Department of Urology, Faculty of Medicine-School of Health Sciences-University of Thessaly, University Hospital of Larissa, Larissa, Greece, lamprosmit@gmail.com.
authors: Lampros
authors: L
authors: Mitrakas
authors: Stavros
authors: S
authors: Gravas
authors: Foteini
authors: F
authors: Karasavvidou
authors: Georgios
authors: G
authors: Dimakopoulos
authors: Georgios
authors: G
authors: Moutzouris
authors: Vasileios
authors: V
authors: Tzortzis
authors: Georgios
authors: G
authors: Koukoulis
authors: Christos
authors: C
authors: Papandreou
authors: Michael
authors: M
authors: Melekos
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000235:genetics* / Q000473:pathology; D009132:Muscles / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019332:Endothelin-1
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