Over-expression of tenascin-C in malignant pleural mesothelioma

Aims:  Tenascin-C is an extracellular matrix glycoprotein known to have anti-adhesive characteristics and to be expressed in various human malignant neoplasms. We hypothesized that the expression of tenascin-C would be increased in human malignant pleural mesothelioma, and its accumulation associated with the prognosis of the patients with this disease.
Methods and results:  Thirty-seven cases of mesothelioma were studied by immunohistochemically using a monoclonal antibody against tenascin-C, and with a semiquantitative scoring system for tenascin-C in different areas of the tumours. In 10 selected cases tenascin-C mRNA in-situ hybridization was also analysed. Since transforming growth factor-beta (TGF-β) is known to induce both the synthesis of tenascin-C and the growth of mesotheliomas, an immunohistochemical analysis of TGF-β1, -β2 and -β3 was also performed. Normal pleura ( n  = 7) and metastatic pleural adenocarcinomas ( n  = 7) were used as controls. Tenascin-C protein was expressed in every histological subtype of malignant mesothelioma, being most prominent in the fibrotic stroma of a tumour, around tumour cells and at the invasive border, whereas tenascin-C mRNA was scarce in tumour cells. The patients with less immunohistochemical expression for tenascin-C tended to live longer ( P  = 0.028 by Fishers' exact probability test). All mesotheliomas showed positivity for at least one isoform of TGF-β.
Conclusions:  In conclusion, high expression of tenascin-C protein in malignant pleural mesotheliomas may play a role in its invasive growth, and might serve as a prognostic marker of the disease.