Components of the plasminogen activation system in uveal melanoma--a clinico-pathological study

In tumour development, proteases such as plasminogen activators (PAs) play a role in degradation of the extracellular matrix and other tissue barriers. Recently, we demonstrated that plasminogen activators, their inhibitors, and urokinase receptor emerge in late stages of cutaneous melanocytic tumour progression. In this study we investigated the expression and distribution of the various components of the PA system and the presence of PA enzyme activity in 45 freshly frozen primary uveal melanoma with known follow-up (14 spindle and 31 non-spindle type) and in metastases (n = 5). Tissue-type PA (t-PA) was found in endothelium of blood vessels and in tumour cells in almost all lesions, and was markedly present at the invasive front (towards the sclera and Bruch's membrane), but no correlation with tumour-related death could be established. Urokinase PA (u-PA) was expressed focally, by only five non-spindle cell melanomas but in all metastases. u-PA expression correlated with occurrence of metastasis. u-PA receptor (u-PAR) was present in one-third of all the tumours examined. Plasminogen activator inhibitors (PAI-1 and PAI-2) were found only focally in approximately 10 per cent of the lesions. Staining of t-PA, u-PA, and PAI was observed in all the metastases. We conclude that in uveal melanoma, u-PA expression may be associated with metastatic disease and accordingly with a poor prognosis. Further research on a larger group of tumours with known follow-up is needed to establish whether u-PA positivity is of additional prognostic value in uveal melanoma.