Purchase this article with an account.
N.V. Laver, S. Kondratiev, R.A. Rao, L.L. Price; Matrix Metalloproteinase–2 (MMP–2) as a Prognostic Factor of Survival in Uveal Malignant Melanomas . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2254.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in the degradation of extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor–induced angiogenesis. The objective of this study was to evaluate the quantitative expression and prognostic value of matrix metalloproteinase–2 (MMP–2) in intraocular malignant melanomas along with a set of additional clinical and histomorphometrical parameters, which can predict patient outcome.
88 cases of uveal malignant melanoma were selected from the files of the Armed Forces Institute of Pathology. The tumors were classified according to clinico–pathological findings. Cell type (CT) and the mean size of the longest nucleoli (MLN) were utilized along with patient survival outcome. Immunohistochemistry was performed on the paraffin embedded melanoma tissues and the bleached tissue sections were probed with antibodies against human MMP–2 (R@D systems Inc). The binding was visualized as a red pigment using the secondary antibody and the Avidin Biotin complex kit (vectastain Elite ABC kit, Vector Laboratories). Using a Q–imaging Micropublisher 5.0 color digital camera, five representative pictures per tumor were taken and analyzed by a computer based system (Olympus Micro Suite, Olympus America, Inc. NY) The degree of staining was expressed as color intensity (CI), average percentage of MMP–2 staining (AVE), and maximal percentage of MMP–2 staining (MAX) per 5 high power fields (x200). Logistic regression was used for statistic analysis.
Patients with higher MMP–2 expression, including AVE and MAX showed a worse overall outcome compared with patients with lower or negative MMP–2 expression (p= 0.0002, odds ratio=1.915; p=0.0001, odds ratio=1.494 respectively). Multivariate analysis using the logistic regression showed a strong correlation between death from metastatic ocular malignant melanoma and the maximal percentage of MMP–2 staining, MLN, and CT (p=0.0004, odds ratio=1.656; p=0.0064, odds ratio=3.593; p=0.0313, odds ratio=5.753 respectively).
In this study, we have quantified the expression of MMP–2 in ocular melanomas using a computer based image analysis. Our results demonstrate that maximal percentage of MMP–2 staining is an important predictor of mortality, along with MLN and CT. They can be collectively used as vital parameters in patient prognosis during histopathological evaluation.
This PDF is available to Subscribers Only