title: Differential expression of angioregulatory matricellular proteins in posterior uveal melanoma.
abstract: Metastases from uveal melanoma, the most common primary malignant eye tumour in adults, develop solely via their vascular bed due to the absence of intraocular lymphatics. The present study investigated the expression in this tumour of three matricellular proteins--Secreted Protein Acidic and Rich in Cysteine (SPARC), thrombospondin 1 (TSP1) and thrombospondin 2 (TSP2)--with putative contrasting roles in the regulation of angiogenesis. Immunohistochemical analysis of the three proteins was carried out in paraffin-embedded specimens from 27 posterior uveal melanomas and was corroborated with Western blot analysis of fresh-frozen samples from seven of the tumours. SPARC immunoreactivity was detected in all specimens and defined two categories of tumour: SPARC-rich (21 of 27 specimens) and SPARC-patchy (six of 27 specimens) uveal melanomas. SPARC-rich tumours had a significantly higher proportion of specimen area occupied by blood vessels (P=0.04) and showed a positive association with the presence of epithelioid-type tumoral cells (P=0.101). TSP1 was not detected by either of the methods in any of the tumours analysed. Some immunopositivity for TSP2 was detected in tumour cells in approximately 40% of specimens, but was not associated with survival, tumour vascularity or any other histopathological indices of survival. The pattern of expression of these matricellular proteins in uveal melanoma is consistent with a cooperative mechanism for establishing an enhanced environment favourable to angiogenesis. Interventions inducing TSP1 expression and/or inhibiting SPARC expression may be candidates for therapies directed towards the inhibition of angiogenesis in posterior uveal melanoma.
authors.affiliation: Unit of Ophthalmology, School of Clinical Sciences, University of Liverpool, UK.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Ordonez
authors.forename: Luminita
authors.initials: L
authors.lastname: Paraoan
authors.forename: Paul
authors.initials: P
authors.lastname: Hiscott
authors.forename: Donna
authors.initials: D
authors.lastname: Gray
authors.forename: Marta
authors.initials: M
authors.lastname: García-Fiñana
authors.forename: Ian
authors.initials: I
authors.lastname: Grierson
authors.forename: Bertil
authors.initials: B
authors.lastname: Damato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002830:Choroid Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000098:blood supply* / Q000378:metabolism*; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism; D015676:Osteonectin / Q000096:biosynthesis*; D019700:Thrombospondin 1 / Q000096:biosynthesis*; D019699:Thrombospondins / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D000099262:Thrombospondin 2
chemical_list: D015676:Osteonectin; D019700:Thrombospondin 1; D019699:Thrombospondins; D000099262:Thrombospondin 2