Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy.
OBJECTIVE
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.
Alyahya
Ghassan Ayish
GA
Section of Eye Pathology, Institute of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Kolko
Miriam
M
Prause
Jan Ulrik
JU
Nielsen
Boye Schnack
BS
Wang
Jinmei
J
Heegaard
Steffen
S
D002830:Choroid Neoplasms / Q000150:complications* / Q000473:pathology; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000150:complications* / Q000473:pathology; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000378:metabolism; D012590:Sclera / Q000201:enzymology / Q000473:pathology; D015422:Scleral Diseases / Q000201:enzymology* / Q000209:etiology*; D013194:Staining and Labeling; D015854:Up-Regulation
D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2