• Open Access

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

Authors

  • Tomohide Tsukahara,

    1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543;
    2. Department of Pathology, Sapporo Medical University School of Medicine, South 1, West 17, Chuo-ku, Sapporo, 060-8556;
    Search for more papers by this author
  • Satoshi Kawaguchi,

    Corresponding author
    1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543;
      To whom correspondence should be addressed. E-mail: kawaguch@sapmed.ac.jp
    Search for more papers by this author
  • Toshihiko Torigoe,

    1. Department of Pathology, Sapporo Medical University School of Medicine, South 1, West 17, Chuo-ku, Sapporo, 060-8556;
    Search for more papers by this author
  • Hiroko Asanuma,

    1. Division of Clinical Pathology, Sapporo Medical University Hospital, South 1, West 16, Chuo-ku, Sapporo, 060-8543;
    Search for more papers by this author
  • Emiri Nakazawa,

    1. Cancer Vaccine Laboratory, Innovation Plaza Hokkaido, Japan Science and Technology Agency, Kita 19, Nishi 11, Kita-ku, Sapporo, 060-0819, Japan
    Search for more papers by this author
  • Kumiko Shimozawa,

    1. Cancer Vaccine Laboratory, Innovation Plaza Hokkaido, Japan Science and Technology Agency, Kita 19, Nishi 11, Kita-ku, Sapporo, 060-0819, Japan
    Search for more papers by this author
  • Yuki Nabeta,

    1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543;
    Search for more papers by this author
  • Shigeharu Kimura,

    1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543;
    2. Department of Pathology, Sapporo Medical University School of Medicine, South 1, West 17, Chuo-ku, Sapporo, 060-8556;
    Search for more papers by this author
  • Mitsunori Kaya,

    1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543;
    Search for more papers by this author
  • Satoshi Nagoya,

    1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543;
    Search for more papers by this author
  • Takuro Wada,

    1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543;
    Search for more papers by this author
  • Toshihiko Yamashita,

    1. Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543;
    Search for more papers by this author
  • Noriyuki Sato

    1. Department of Pathology, Sapporo Medical University School of Medicine, South 1, West 17, Chuo-ku, Sapporo, 060-8556;
    Search for more papers by this author

To whom correspondence should be addressed. E-mail: kawaguch@sapmed.ac.jp

Abstract

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)

Ancillary