Prognostic significance of HLA class I expression in osteosarcoma defined by anti‐pan HLA class I monoclonal antibody, EMR8‐5

• Published in: Cancer science Vol. 97; no. 12; pp. 1374 - 1380
• Main Authors: Tsukahara, Tomohide, Kawaguchi, Satoshi, Torigoe, Toshihiko, Asanuma, Hiroko, Nakazawa, Emiri, Shimozawa, Kumiko, Nabeta, Yuki, Kimura, Shigeharu, Kaya, Mitsunori, Nagoya, Satoshi, Wada, Takuro, Yamashita, Toshihiko, Sato, Noriyuki
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.12.2006; Blackwell
• Subjects: Adolescent; Adult; Antibodies, Monoclonal - immunology; beta 2-Microglobulin - genetics; beta 2-Microglobulin - immunology; beta 2-Microglobulin - metabolism; Biological and medical sciences; Bone Neoplasms - immunology; Bone Neoplasms - metabolism; Bone Neoplasms - secondary; Child; Diseases of the osteoarticular system; Female; Histiocytoma, Malignant Fibrous - immunology; Histiocytoma, Malignant Fibrous - pathology; Histiocytoma, Malignant Fibrous - secondary; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Humans; Immunoenzyme Techniques; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medical sciences; Middle Aged; Original; Osteosarcoma - diagnosis; Osteosarcoma - immunology; Osteosarcoma - metabolism; Papillomavirus; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Sarcoma - immunology; Sarcoma - metabolism; Sarcoma - secondary; Soft Tissue Neoplasms - immunology; Soft Tissue Neoplasms - metabolism; Soft Tissue Neoplasms - pathology; Survival Rate; T-Lymphocytes, Cytotoxic - immunology; Tumors; Tumors of striated muscle and skeleton; Human; HLA-System; Cancerology; Prognosis; Sarcoma; Osteosarcoma; Major histocompatibility system; Diseases of the osteoarticular system; Malignant tumor; Monoclonal antibody; Bone; Class I histocompatibility antigen
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2006.00317.x

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 β‐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. (Cancer Sci 2006; 97: 1374–1380)