HUMAN-LEUKOCYTE ANTIGEN CLASS-I EXPRESSION - MARKER OF POOR-PROGNOSISIN UVEAL MELANOMA

Purpose. Because the expression of human leukocyte antigen (HLA) antig ens is important for immunologic recognition of tumor cells, we determ ined expression of locus-specific HLA class I antigens in uveal melano ma and tested whether the level of HLA expression was related to progn osis or associated with known prognostic parameters. Methods. Expressi on of HLA-A and -B antigens was determined on 30 formalin-fixed and pa raffin-embedded sections of uveal melanoma by immunohistochemistry wit h locus-specific monoclonal antibodies and scored semiquantitatively. Results. The level of expression of HLA-A and -B varied between uveal melanomas. Expression levels of HLA-A and -B were significantly correl ated (P = 0.02). High HLA-B expression was significantly correlated wi th the presence of epithelioid cells (P = 0.04) in the tumor. Expressi on levels of HLA-A as well as of KLA-B, cell type, mitotic rate, Mib-1 score, and largest tumor diameter were significant predictive factors for survival. High expression of HLA-A and -B was associated with a d ecreased survival. Multiple Cox regression analysis with stepwise sele ction of covariates showed that the contribution of HLA-A expression t o survival (P = 0.0003) exceeded that of tumor diameter (P = 0.02) and Mib-1 score (P = 0.04). Conclusions. Lack of expression of HLA-A as w ell as of HLA-B antigens on uveal melanoma is correlated with a better patient survival. Our data suggest that shedding of uveal melanoma mi crometastases with a low expression of HLA. class I into the systemic circulation may facilitate their removal and prevent the development o f metastases. These findings support a protective role for natural kil ler cells in the development of metastatic disease in uveal melanoma.