Department of Urology, University of Duisburg-Essen, Germany; Department of Urology, Medical University of Vienna, Austria.
Endostatin, the proteolytic fragment of collagen XVIII, is an inhibitor of angiogenesis and tumor growth. Interestingly, elevated circulating endostatin levels have been found to correlate with poor patients' prognosis in several cancers. The aim of this study was to assess the prognostic value of endostatin in bladder cancer (BC) and to gain insight into the mechanisms involved in its production. This retrospective study included a total of 337 BC patients and 103 controls. Collagen XVIII gene expression was analyzed using real-time PCR (n=82). Endostatin tissue localization was assessed by immunohistochemistry (n=27). Endostatin serum (n=87) and urine (n=153) levels were determined by ELISA. In 12 cases both serum and paraffinized tissue samples from the same patients were available. We found decreased collagen XVIII tissue expression and increased endostatin urine and serum concentration in samples of BC patients compared to controls. High serum endostatin levels correlated with the presence of lymph node metastases and MMP-7 concentrations and were independently associated with poor metastasis-free and disease-specific survival. Immunohistochemical analysis revealed a strong endostatin staining in the wall of tumor associated blood vessels in superficial but not in muscle-invasive BCs. Based on these, we concluded that elevated endostatin levels in BC patients are the consequence of enhanced extracellular matrix degradation and are independent from collagen XVIII expression. Furthermore, serum endostatin levels may provide prognostic information independent from histopathological parameters and may therefore help to optimize therapy decisions. Loss of endostatin expression in tumor accociated blood vessels might represent an important step supporting tumor induced angiogenesis.
Written by:
Szarvas T, László V, Dorp FV, Reis H, Szendrői A, Romics I, Tilki D, Rübben H, Ergün S. Are you the author?
Reference: Int J Cancer. 2011 Aug 3. Epub ahead of print.
doi: 10.1002/ijc.26343
PubMed Abstract
PMID: 21815140
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