Proteoglycans and WT1 as markers for distinguishing adenocarcinoma, epithelioid mesothelioma, and benign mesothelium

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Abstract

Malignant mesothelioma is a tumour frequently accompanied by an effusion with elevated hyaluronan levels. To distinguish malignant mesothelioma, adenocarcinoma, and reactive benign mesothelium with cytological and histological methods including immunocytochemistry is a major diagnostic challenge. The Wilms' tumour susceptibility gene 1 (WT1), expressed during transition of mesenchyme to epithelial tissues, is regarded as a marker for the mesothelial lineage. Its effect on the cell phenotype may be regulated via the syndecans, i.e. proteoglycans on the cell surface. To determine how WT1, proteoglycans, and hyaluronan synthase are expressed in mesothelioma, adenocarcinoma, and reactive benign mesothelium, we studied these molecules at the mRNA and protein levels, with the additional purpose of finding diagnostic parameters. Adenocarcinoma cells produced more mRNA for syndecan-1, but cells derived from mesothelium expressed WT1, biglycan, and larger amounts of syndecan-2. The difference in gene expression of these two syndecans was best monitored by the ratio between them. Syndecan-4 was highly expressed in all malignant cell lines, this expression being 1.7-5 times greater than in benign mesothelial cells. Although hyaluronan synthase-1 and versican could not distinguish between the three conditions, versican expression was associated with a high rate of proliferation. These findings suggest that syndecan-1 and syndecan-2 together may be useful diagnostic markers, with stronger staining for the latter epitope in mesothelial tissues. The alternating appearance of these two syndecans can be shown not only by RT-PCR and FACS in vitro, but also by immunohistochemistry on clinical material.

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