Syndecan-1 expression in malignant mesothelioma: correlation with cell differentiation, WT1 expression, and clinical outcome.
Syndecan-1 binds basic fibroblast growth factor (bFGF), modulates neovascularization, plays a role in epithelial differentiation and is up-regulated by WT1. Malignant mesothelioma of the pleura is one of the most aggressive tumours known and expresses high levels of angiogenic growth factors. This study has analysed syndecan-1 expression in mesothelioma tumours and cell lines by immunohistochemistry and immunoblotting, using anti-syndecan-1 antibody directed against the core protein, and has examined its relation to morphology, bFGF, WT1, and intra-tumoural microvascular density (IMD). Shedding of syndecan-1 in the conditioned medium of mesothelioma cell lines was detected in variable amounts. These studies indicate that (1) there is no correlation of syndecan-1 with either bFGF expression or IMD in mesotheliomas in vivo; (2) syndecan-1 is strongly expressed in the epithelial type of mesothelioma and in the epithelial component of biphasic mesotheliomas and the expression is reduced or lost in sarcomatoid differentiation; together with the finding that (3) syndecan-1 correlates with WT1 immuno-expression, this suggests that syndecan-1 might relate to the differentiation state of mesothelial/mesothelioma cells; and (4) syndecan-1-positive tumours are associated with a longer survival (p = 0.02) than mesotheliomas with no or little syndecan-1 expression, on univariate analysis. These findings therefore indicate that syndecan-1 can be an important prognostic indicator in mesotheliomas and its loss may be important in the epithelial-mesenchymal transformation of mesothelioma cells.
Kumar-Singh
S
S
Department of Pathology, University of Antwerp (UIA), Belgium.
Jacobs
W
W
Dhaene
K
K
Weyn
B
B
Bogers
J
J
Weyler
J
J
Van Marck
E
E
D000230:Adenocarcinoma / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002454:Cell Differentiation; D016009:Chi-Square Distribution; D004268:DNA-Binding Proteins / Q000032:analysis*; D004848:Epithelium / Q000737:chemistry / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000032:analysis; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis*; D008654:Mesothelioma / Q000098:blood supply / Q000737:chemistry* / Q000401:mortality; D009389:Neovascularization, Pathologic; D011233:Precipitin Tests; D011379:Prognosis; D011509:Proteoglycans / Q000032:analysis*; D015996:Survival Rate; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors / Q000032:analysis*; D025721:WT1 Proteins
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D016222:Fibroblast Growth Factor 2; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors; D025721:WT1 Proteins; C508241:SDC1 protein, human; C071927:perlecan