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G Anastassiou, V Rebmann, S Wagner, H Grosse-Wilde, N Bornfeld; HLA Class I expression in uveal melanoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2209.
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Purpose: As the expression of classical and non-classical HLA antigens is crucial for the recognition and elimination of tumor cells by cytotoxic T- and/or NK-cells, we analyzed the HLA-A,B,C and G expression in uveal melanoma of 18 patients. Methods: Tumor specimens and EDTA plasma samples from 18 patients treated by primary enucleation or tumor resection for primary uveal melanoma in the University Eye Clinic of Essen were collected immediate after surgery. After solubilisation of tumor tissue and specific immunoprecipitation of classical HLA-A,B,C and non-classical HLA-G antigens the tumor samples were analyzed by one dimensional isoelectrical focusing (1D-IEF) and Western Blotting. In parallel, patients were typed for HLA-A,B,C class I antigens by PCR-SSP. In addition, HLA-A2 and HLA-G expression was investigated by immunohistochemistry (ICH) in paraffin embedded tumor material of these patients. Results: In 10 out of 18 tumors (56 %) full HLA-A and B antigen expression pattern was detected by 1D-IEF. In 6 tumor tissues (33 %) a HLA class I allele was missing (HLA-A2, A28, A29, B13, B18, B55), in 1 case an haplotypic loss (HLA-A2, B44) and in an other case an allele specific loss combined with haplotypic loss (HLA-A26,32, B41) were observed. HLA-C and HLA-G antigens were detectable in none of the tumor samples by the 1D-IEF. Even in the ICH only 2 out of 18 (11 %) tumors showed an immunoreactivity with the anti-HLA-G monoclonal antibody. ICH analysis for HLA-A2 expression confirmed the results of 1D-IEF. Conclusion: A considerable portion of the uveal melanomas tested showed a loss of classical HLA class I antigens which might enable them to escape from the immunosurveillance of cytotoxic T-cells. However, HLA-C and G antigens were not expressed in uveal melanoma implying a possible susceptibility for NK-cell mediated lysis.
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