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. Copyright © 1999 John Wiley & Sons, Ltd.

A comparison of ocular melanocyte and uveal melanoma cell invasion and the implication of α1β1, α4β1 and α6β1 integrins

“…In the present study, we compared secretion of MMP-2 and MMP-9 with invasiveness and other prognostic indicators. No correlation was found between secretion of either MMP and invasiveness, although recent evidence has suggested that MMP-2 is correlated with indicators of poor prognosis in uveal melanoma 33. One explanation for the lack of correlation is that MMP-2 and MMP-9 degrade mainly type IV collagenase and gelatin, and fibronectin was used as a barrier to invasion in this study, as previous investigations had established fibronectin as the preferred substrate for uveal melanoma cell attachment 34.…”

Type IV collagen and its degradation in paralyzed human muscle: Effect of functional electrical stimulation

“…Ten individuals (men/women: 8/2) with spinal cord injury [level: C6 to T6; years since injury: 12.5 (2-23) years (mean and range); age: 35 (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45) years; mean weight: 78 ± 3.8 (SE) kg] participated in the present study, which was approved by the Municipal Ethical Committee of Copenhagen. Six were tetraplegic and four were paraplegic.…”

“…ELISAs were performed on 96well microtiter plates using standard protocols as described elsewhere. 45 Briefly, a 96-well microtiter plate (Nunc Maxisorb; Nalge Nunc International, Roskilde, Denmark) was coated with a specific monoclonal antibody against the analyte. A polyclonal antibody produced in chicken against the ana-lyte was used as a secondary antibody.…”

Matrix metalloproteinase biology applied to vitreoretinal disorders

“…Evidence has recently emerged that MMP-2 may be a prognostic marker in uveal melanoma. An immunohistochemical study of 29 uveal melanomas by Vaisanen and colleagues demonstrated that positive immunostaining for MMP-2 in tumour cells correlated significantly with poorer 5 year relapse free and overall survival rates and a higher incidence of visceral metastases 122. Levels of MMP-2, TIMP-1, and TIMP-2 in the vitreous, where available for analysis, were not elevated compared with controls, and had no prognostic significance.…”