title: Reduced expression of TAP-1 and TAP-2 in posterior uveal melanoma is associated with progression to metastatic disease.
abstract: In order to determine the effects of the loss or reduced expression of molecules associated with antigen presentation (transporter associated with antigen presentation [TAP]-1, TAP-2, low molecular weight protein [LMP]-2 and LMP-7), we examined the expression of these molecules in primary uveal melanoma lesions. Paraffin-embedded sections from 29 primary uveal melanoma lesions were analysed for expression of TAP-1, TAP-2, LMP-2 and LMP-7 using specific primary antibodies followed by a three-stage immunoperoxidase technique. Microscopic examination was undertaken to determine differences in expression of these molecules on the tumour and the surrounding stroma. Overall, 72% (21 out of 29) of the tumours showed some loss or reduced expression of TAP-1, TAP-2, LMP-2 and/or LMP-7. Statistical analysis of these results showed that progression to metastatic disease was strongly associated with reduced expression of TAP-1 (P < 0.05) and TAP-2 (P < 0.01), taking patient age, tumour site and histology into account. We conclude that the reduced expression of molecules important in eliciting an immune response, such as TAP-1 and TAP-2, may facilitate the metastatic spread of uveal melanoma lesions and may have important implications for prospective immunotherapy.
authors.affiliation: Institute of Cancer Studies, G Floor, Medical School, Beech Hill Road, Sheffield, UK.
authors.forename: A C
authors.initials: AC
authors.lastname: Cresswell
authors.forename: K
authors.initials: K
authors.lastname: Sisley
authors.forename: D
authors.initials: D
authors.lastname: Laws
authors.forename: M A
authors.initials: MA
authors.lastname: Parsons
authors.forename: I G
authors.initials: IG
authors.lastname: Rennie
authors.forename: A K
authors.initials: AK
authors.lastname: Murray
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010544:Peroxidases / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014604:Uveal Neoplasms / Q000378:metabolism*
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D010544:Peroxidases