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NV Laver, A Yijayvargiya, R Pathi, S Chintala, E Fini; Uveal Malignant Melanoma and Tissue Metalloproteinase Profiles . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1118.
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Purpose: Matrix Metalloproteinases (MMPs) are a family of enzymes that control tissue remodeling. They have been implicated in numerous pathologies including tumor progression. The purpose of the study was to determine if there is a correlation between the immunohistochemical profile of MMP’s in ocular melanomas, the tumor cell type and metastatic potential. Methods: We chose a panel of antibody probes representative of three MMP subfamilies: the gelatinases (MMP-2 and MMP-9), the collagenases (MMP-13), and the membrane-bound MMPs (MMP-14). Intraocular primary malignant melanomas (n=12) and control tissues with other pathologies (n=9) were formalin-fixed and paraffin-embedded. Bleached tissue sections were probed with antibodies against human MMPs (R&D Systems, Inc, Chemicon International Inc.) and binding was visualized using a secondary antibody and employing an Avidin Biotin complex kit (Vectasin Elite ABC kit, Vector Laboratory). A scoring system was utilized for both percent of tumor staining (1: ≷25%, 2:25-75% and 3: ≷75%) and intensity of staining (mild:1; moderate :2 and severe:3) Most of the patients were males (9/12) ranging in age from 32-73 years old. Most tumors (n=10) showed a mixed cell population; two showed a spindle cell population only. The tumor size ranged from 6-20 mm and showed mitotic figures ranging from 1-24 per HPF. Two cases had extraocular extension into the orbit and optic nerve area, respectively. Two patients received radiation plaque treatment before enucleation. Two patients died a year after initial diagnosis of unrelated causes. Two cases of retinoblastoma, one eyelid nevus, a phthisical eye, and three eyes from autopsy cases of patients without ocular pathology were utilized as controls Results: Most tumors (10-11/12) showed cytoplasmic staining for both MMP2, MM9 and MMP13 with over 50% of the cases showing 25-75% of cytoplasmic tumor staining or higher. In contrast, nine of the 12 tumors showed positive reactivity to MMP14; of these, eight showed 75% of staining with MMP2, MMP9 and MMP13 and in addition 25-75% staining with MMP14. A single necrotic tumor did not express immunoreactivity to any MMP. We observed no correlation between percent of tumor staining and size of the tumor. MMP immunostaining was associated predominantly with epithelioid and pigmented tumor cells. Conclusion: In these preliminary studies, we have identified distinct MMP immunostaining patterns in different ocular melanomas that might be used to predict the aggressiveness of tumor growth.
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