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Matrix Metalloproteinase-2 Is Expressed in Melanoma-Associated Spongiform Scleropathy

¹From the Section of Eye Pathology, Institute of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; and the ²Finsen Laboratoriet, Finsencentret, Rigshospitalet, Copenhagen, Denmark.

PURPOSE. To correlate the expression of matrix metalloproteinases (MMPs) with melanoma-associated spongiform scleropathy (MASS) and scleral tumor invasion in eyes with uveal melanoma.

METHODS. Eleven specimens with MASS and 11 eyes without MASS were investigated. Sections were examined for MMP-1, -2, -9, and -13 mRNA expression by in situ hybridization with ³⁵S-radiolabeled riboprobes. Immunohistochemical studies of the same specimens were conducted with MMP-2-specific antibodies. For double-labeling experiments, primary MMP-2-specific antibodies and antibodies binding to fibroblasts and macrophages were used.

RESULTS. MMP-2 mRNA expression was detected in 10 (91%) of 11 eyes with MASS and scleral tumor invasion. In eight (73%) of these cases, the expression signals were seen in numerous scleral fibroblasts. In melanoma cases without MASS, MMP-2 mRNA expression was detected in four (36%) cases, and only one (9%) showed numerous positive cells. Tumor-infiltrating macrophages were found to harbor MMP-2, shown by a double-labeling experiment. The MMP-2 expression by immunostaining coincides with MMP-2 expression by in situ hybridization. No MMP-2 expression was detected in the tumor cells.

CONCLUSIONS. MASS is considered a tumor-induced scleral degradation process. There is a significantly higher expression of MMP-2 in MASS-positive areas, indicating that MMP-2 is involved in the development of MASS and that MMP-2 is produced by scleral fibroblasts under the influence of tumor cells and/or tumor-infiltrating macrophages. These changes may represent a step in the invasion of uveal melanoma by facilitating the spread of tumor cells through the sclera.