Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy

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 (35)S-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.