Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer

Tibor Szarvas, Henning Reis, Gero Kramer, Shahrokh F. Shariat, Frank Vom Dorp, Stephan Tschirdewahn, Kurt W. Schmid, Ilona Kovalszky, Herbert Rübben

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32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)674-682
Number of pages9
JournalHuman pathology
Volume45
Issue number4
DOIs
Publication statusPublished - Apr 2014

Keywords

  • Bladder cancer
  • CD138
  • Prognosis
  • Serum
  • Syndecan-1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Szarvas, T., Reis, H., Kramer, G., Shariat, S. F., Vom Dorp, F., Tschirdewahn, S., Schmid, K. W., Kovalszky, I., & Rübben, H. (2014). Enhanced stromal syndecan-1 expression is an independent risk factor for poor survival in bladder cancer. Human pathology, 45(4), 674-682. https://doi.org/10.1016/j.humpath.2013.10.036