title: Matrix metalloproteinase-2 is expressed in melanoma-associated spongiform scleropathy.
abstract: 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.
authors.affiliation: Section of Eye Pathology, Institute of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ghassan Ayish
authors.initials: GA
authors.lastname: Alyahya
authors.forename: Miriam
authors.initials: M
authors.lastname: Kolko
authors.forename: Jan Ulrik
authors.initials: JU
authors.lastname: Prause
authors.forename: Boye Schnack
authors.initials: BS
authors.lastname: Nielsen
authors.forename: Jinmei
authors.initials: J
authors.lastname: Wang
authors.forename: Steffen
authors.initials: S
authors.lastname: Heegaard
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2