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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. Copyright © 1998 John Wiley & Sons, Ltd.