Matrix metalloproteinase-2 (MMP-2) immunoreactive protein--a new prognostic marker in uveal melanoma?

Abstract

Uveal melanoma is the most common primary intraocular tumour. Once haematogenous metastasis has occurred, there is no cure for the disease and there is an obvious need for new biological prognostic markers to estimate the risk of metastasis. In this study, the expression of matrix metalloproteinase-2 (MMP-2) was characterized immunohistochemically in 29 human uveal melanomas. Enzyme-linked immunoassays and gelatin zymographies were assessed in order to quantify the expression of gelatinases A and B, as well as the tissue inhibitor of metalloproteinases (TIMPs), in the vitreous body. A total of 49 per cent of the uveal melanomas displayed a positive immunoreaction for MMP-2 in melanoma cells, the epithelioid cells showing the most frequent staining. There was no correlation between the positivity of MMP-2 staining and the size of the primary tumour, gender or age. The expression of MMP-2 was associated with a dismal prognosis: the 5-year overall survival rate for MMP-2-positive cases was significantly inferior to that of the MMP-2 negative cases, 49 per cent vs. 86 per cent, respectively (p=0.02). A patient group at high risk of metastatic disease was identified; only 38 per cent of patients with a MMP-2-positive non-spindle cell uveal melanoma survived for 5 years. The analyses of MMPs or TIMPs in the vitreous body had no prognostic value. Positive immunostaining for MMP-2 was observed in the retinal pigment epithelium, corneal epithelium, and fibroblasts in the ciliary body and choroid. It is concluded that immunohistochemical analysis of MMP-2 may help to predict a risk of metastasis in uveal melanoma.