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K. Subramanian, J. Biswas, A.S. Lakshmi, P. Vaijayanthi, M.P. Shanmugam, D. Abhyankar, S. Ferrone; HLA Class I Antigens, ß2-microglobulin, HLA Class II Antigens and Antigen Processing Molecules Expression in Uveal Melanoma: Correlation with Clinicopathological Parameters . Invest. Ophthalmol. Vis. Sci. 2003;44(13):929.
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Purpose: We studied the immunoexpression of HLA class I antigen, ß2-microglobulin and HLA class II antigen and the antigen processing molecules: transporters associated with antigen processing: TAP 1, the proteasomal components: low molecular weight proteins: LMP 2, LMP10, the binding protein- tapasin and chaperone protein- calnexin in uveal melanomas and correlated clinicopathologically. Methods: Monoclonal antibodies to HLA class I antigen , ß2-microglobulin, HLA class II antigen, and antigen processing molecules were analyzed in primary uveal melanoma lesions by immunoperoxidase staining on 45 archival tumors and correlated with cell types, largest tumor diameter,nuclear grade,mitosis,tumor infiltrating lymphocytes and extrascleral extension. Immunoanalysis was done by a semi -quantitative method. (International Histocompatibility Working Group). Data was analyzed for statistical significance. Results: Immunoexpression of HLA class I, ß2-microglobulin, HLA class II antigen and antigen-processing molecules are concordant in all the tumors. HLA class I antigen, ß2-microglobulin, HLA class II antigen and antigen processing molecules are down regulated in 35 (100%) tumors with no extrascleral extension. Among the 10 tumors with extrascleral extension, HLA class I antigen, ß2-m, HLA class II antigen and antigen processing molecules are positive in 6 (60%) tumors with liver metastasis and down regulated in 4 (40%) tumors with no liver metastasis. Down regulation of HLA class molecules and antigen processing molecules are significant in tumors with no extension. (p <0.001) There is no correlation between largest tumor diameter,tumor infiltrating lymphocytes, nuclear grade, and mitosis with immunoreactivity. Negative expression in the spindle melanoma is significant. (p <0.001) Conclusions: Decreased immunoreactivity of HLA class 1, ß2-microglobulin, HLA class II antigens and antigen processing molecules have prognostic significance in uveal melanoma. Antigen processing molecules are necessary for expression of HLA class I antigen. Concordance in the expression of MHC class I expression and antigen-processing molecules suggests defects in the regulatory mechanisms that control their expression and not structural defects in the corresponding genes.
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