title: Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer.
abstract: In this study, we assessed the changes and prognostic relevance of syndecan-1 (SDC1) tissue and serum levels in bladder cancer (BC). SDC1 levels were analyzed in 213 samples (119 paraffin-embedded and 79 serum samples of BC patients and 15 controls) using immunohistochemistry and enzyme-linked immunosorbent assay. Results were correlated with clinicopathological characteristics and follow-up data, as well as previously determined serum levels of angiogenic factors (basic fibroblast growth factor, endostatin, angiostatin, angiopoietin, vascular endothelial growth factor, Tie2 and MMP-7). SDC1 staining was present in the cell membrane of normal bladder epithelium and non-muscle-invasive BC cells but was absent in a significant proportion of muscle-invasive carcinomas (P < .001). In contrast, stromal SDC1 expression was enhanced in muscle-invasive compared to non-muscle-invasive BCs (P = .001). Serum concentrations of the SDC1 ectodomain were higher in muscle-invasive BCs compared to controls or non-muscle-invasive carcinomas (P < .001 each). Lymph node-positive cases had the highest SDC1 serum concentrations (P < .001). SDC1 expression in stromal cells was independently associated with survival (hazard ratio = 2.034, 95% confidence interval 1.176-3.519, P = .011). SDC1 serum concentrations correlated with those of endostatin and matrix metalloproteinase 7. Loss of SDC1 in tumor cells and the parallel increase of serum SDC1 ectodomain concentration in high-stage, high-grade BCs suggest the involvement of SDC1 shedding in BC progression. In addition, high preoperative SDC1 serum levels may help to identify patients with lymph node metastases, supporting therapeutic decision-making. Presence of SDC1 in tumor stroma is an independent risk factor for patient survival and may therefore be used to select patients for more aggressive therapy.
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, 1090 Vienna, Austria. Electronic address: sztibusz@gmail.com.
authors.forename: Tibor
authors.initials: T
authors.lastname: Szarvas
authors.affiliation: Institute of Pathology and Neuropathology, Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Reis
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, 1090 Vienna, Austria.
authors.forename: Gero
authors.initials: G
authors.lastname: Kramer
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, 1090 Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Vom Dorp
authors.affiliation: Department of Urology, Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Tschirdewahn
authors.affiliation: Institute of Pathology and Neuropathology, Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Kurt W
authors.initials: KW
authors.lastname: Schmid
authors.affiliation: 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary.
authors.forename: Ilona
authors.initials: I
authors.lastname: Kovalszky
authors.affiliation: Department of Urology, Faculty of Medicine, University of Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Rübben
mesh_terms: D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012372:ROC Curve; D012307:Risk Factors; D053668:Syndecan-1 / Q000032:analysis / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C508241:SDC1 protein, human; D053668:Syndecan-1
keywords: Bladder cancer; CD138; Prognosis; Serum; Syndecan-1