Expression of classic and nonclassic HLA class I antigens in uveal melanoma.

PURPOSE Because the expression of classic and nonclassic 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 specimens from 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, Essen, Germany, were collected immediate after surgery. After solubilization of tumor tissue and specific immunoprecipitation of classic HLA-A, -B, and -C and nonclassic HLA-G antigens the tumor samples were analyzed by one-dimensional isoelectric focusing (1D-IEF) and Western blot analysis. In parallel, patients were typed for HLA-A, -B, and -C class I antigens by PCR with sequence-specific primers (PCR-SSP). In addition, HLA-A2 and -G expression was investigated by immunohistochemistry in paraffin-embedded tumor sections from these patients. RESULTS In 9 (50%) of 18 specimens, a full HLA-A and -B antigen expression pattern was detected by 1D-IEF. In six (33.3%) tumor specimens, an HLA class I allotype was missing (HLA-A2, -A28, -A29, -B18, -B35, and -B55), in two cases a haplotypic loss (HLA-A2, -B44 and HLA-A2, -B13) and in another case an allotype-specific loss combined with a haplotypic loss (HLA-A26, -A32, -B41) were observed. HLA-C and -G antigens were not detectable in any of the tumor samples by biochemical methods used. CONCLUSIONS A considerable portion of the uveal melanomas tested showed a loss of classic HLA class I antigens, which may enable them to escape from the immunosurveillance of cytotoxic T cells. HLA-C and -G antigens were not found in uveal melanoma tissue implying a susceptibility for NK lysis.