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Background: Abnormalities in the expression of human leucocyte antigens (HLA) by tumour cells impair cellular immune responses promoting immune evasion and tumour survival. To date, studies analysing HLA class I and class II expression levels in malignant fibrous histiocytomas, fibrosarcomas and dermatofibrosarcoma protuberans are limited., Aims: Therefore, we investigated the in vivo expression profile of HLA class I and class II antigens in 99 malignant fibrous histiocytomas, 20 fibrosarcomas and 34 dermatofibrosarcoma protuberans from different anatomical sites., Material and Methods: Immunohistochemistry using monoclonal antibodies to HLA class I and class II antigens was used to define the expression levels of these antigens on respective tumour samples., Results: Frequent loss or downregulation of HLA class I and class II expression in malignant fibrous tumours was observed for the different types of tumours examined., Discussion: The data presented suggest for the first time a high frequency of HLA class I and class II abnormalities in malignant fibrous histiocytomas, fibrosarcomas and dermatofibrosarcoma protuberans in vivo., Conclusion: This information might be useful in the practical and clinical design of tumour vaccination strategies., (© 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.)

With the goal of establishing efficacious peptide-based immunotherapy for patients with bone and soft tissue sarcomas, we previously identified the cytotoxic T lymphocyte-defined osteosarcoma antigenic gene Papillomavirus binding factor. The present study was designed to determine the status of HLA class I expression in osteosarcoma and other bone and soft tissue sarcomas. Seventy-four formalin-fixed paraffin-embedded specimens of various bone and soft tissue sarcomas, including 33 osteosarcomas, were stained with the anti-HLA class I monoclonal antibody EMR8-5, which we recently generated. The expression of HLA class I was lost or downregulated in 46 of these specimens (62%). With respect to osteosarcoma, loss or downregulation of HLA class I expression was seen in 13 (52%) of 25 primary tumors and seven (88%) of eight metastatic tumors. In six of 11 HLA class I-negative osteosarcoma specimens, the expression of beta-2 microglobulin was also lost. Subsequently the prognostic significance of HLA class I expression was analyzed in 21 patients with osteosarcoma who had completed multidrug neoadjuvant chemotherapy and undergone adequate surgery. Patients with osteosarcoma highly expressing HLA class I showed significantly better overall and event-free survival than those with HLA class I-negative osteosarcoma. In contrast, such prognostic significance of HLA class I expression was not found in 15 patients with malignant fibrous histiocytoma of soft tissue. These findings suggest that the class I-restricted cytotoxic T lymphocyte pathway plays a major role in immune surveillance of patients with osteosarcoma.