title: Serum endostatin levels correlate with enhanced extracellular matrix degradation and poor patients' prognosis in bladder cancer.
abstract: 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 patients with BC 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 patients with BC 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 patients with BC 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 associated blood vessels might represent an important step supporting tumor-induced angiogenesis.
authors.affiliation: Department of Urology, University of Duisburg-Essen, Germany. sztibusz@gmail.com
authors.forename: Tibor
authors.initials: T
authors.lastname: Szarvas
authors.forename: Viktória
authors.initials: V
authors.lastname: László
authors.forename: Frank
authors.initials: F
authors.lastname: Vom Dorp
authors.forename: Henning
authors.initials: H
authors.lastname: Reis
authors.forename: Attila
authors.initials: A
authors.lastname: Szendröi
authors.forename: Imre
authors.initials: I
authors.lastname: Romics
authors.forename: Derya
authors.initials: D
authors.lastname: Tilki
authors.forename: Herbert
authors.initials: H
authors.lastname: Rübben
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D003094:Collagen / Q000096:biosynthesis; D018572:Disease-Free Survival; D043169:Endostatins / Q000097:blood* / Q000652:urine; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012189:Retrospective Studies; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C509350:COL28A1 protein, human; D043169:Endostatins; D003094:Collagen; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7