Human osteosarcoma expresses specific ephrin profiles

Implications for tumorigenicity and prognosis

Authors

  • Antiopi Varelias Ph.D.,

    1. Department of Orthopedics and Trauma, The Queen Elizabeth Hospital, Woodville, South Australia, Australia
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  • Simon A. Koblar B.M.B.S., Ph.D.,

    1. Department of Medicine, The University of Adelaide, The Queen Elizabeth Hospital, Woodville, South Australia, Australia
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  • Prudence A. Cowled Ph.D.,

    1. Department of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, Woodville, South Australia, Australia
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  • Christopher D. Carter M.B.B.S.,

    1. Drs. King & Mower, Histopathology and Cytopathology, Unley, South Australia, Australia
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  • Mark Clayer M.B.B.S., M.D.

    Corresponding author
    1. Department of Orthopedics and Trauma, The Queen Elizabeth Hospital, Woodville, South Australia, Australia
    • Department of Orthopedics and Trauma, The Queen Elizabeth Hospital, 28 Woodville Road, Woodville, South Australia, Australia, 5011
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    • Fax: 61-8-8222-7068


Abstract

BACKGROUND

The molecular mechanisms underlying malignancy of osteosarcoma are unknown. It has been reported that eph receptor protein tyrosine kinases and their ligands, ephrins, are associated with increased tumorigenicity in patients with breast carcinoma and melanoma. The expression and role of eph/ephrins in human osteosarcoma has not yet been characterized.

METHODS

Ephrin-A1, ephrin-A3, ephrin-A4, ephrin-A5, ephrin-B1, ephrin-B2, and ephrin-B3 mRNA expression was examined by reverse transcription polymerase chain reaction analysis in nine specimens of human osteosarcoma tissue and five human osteosarcoma cell lines. Ephrin-B1 protein expression was detected immunohistochemically in human osteosarcoma tissue. Clinicopathologic correlation was made between the osteosarcoma specimens and their ephrin expression profiles.

RESULTS

Normal bone specimens, osteosarcoma tissue specimens, and osteosarcoma cell lines expressed a distinct mRNA profile of ephrin-A1, ephrin-A4, and ephrin-B2. A second mRNA profile that included ephrin-A3, ephrin-A5, and ephrin-B1 was expressed by a subset of tumors. The expression of ephrin-B1 was correlated with a poorer clinical prognosis. Ephrin-B1 protein was expressed by osteosarcoma cells and blood vessels.

CONCLUSIONS

The results of this study suggest that ephrin-B1 expressed by osteosarcoma may be a poor prognostic marker through increased tumorigenicity. Cancer 2002;95:862–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10749

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