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Prognostic value of indoleamine 2,3-dioxygenase expression in high grade osteosarcoma

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Abstract

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolising enzyme inducing immune tolerance. Some reports have noted a clinical correlation between IDO expression and outcome in some malignant tumors. This study aimed to investigate IDO expression as related to prognosis in osteosarcoma. IDO expression was immunohistochemically scored as five grades. IDO was expressed in most of the cases. Univariate analysis revealed no significant correlation between IDO staining intensity and various variables including sex, age, anatomical site, chemotherapy regimen, necrosis after chemotherapy, and surgical stage. Patients with high IDO expression had significantly lower metastasis-free survival (P = 0.016) and overall survival (P = 0.005). On univariate analysis, age over 20 years and high IDO expression were found to be independent risk factors of lower overall survival and metastasis-free survival. On multivariate analysis, there was no significant correlation between high IDO expression and metastasis-free survival (P = 0.070) and overall survival (P = 0.066). The immune tolerance mediated through IDO may have an important role in the tumorigenesis of osteosarcoma and may exert an impact on the clinical outcome, and thus may lend itself as a therapeutic target of immunotherapy for osteosarcoma.

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Abbreviations

IDO:

Indoleamine 2,3-Dioxygenase

AJCC:

American Joint Committee on Cancer Staging System

PBS:

Phosphate buffered saline

DOD:

Dead of disease

HR:

Hazard ratio

CI:

Confidence interval

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Acknowledgments

We thank Dr. Mitsutoshi Uchibori for technical advice, Miss Eri Ishihara for secretarial assistance, and Drs. K. Ino and E. Yamamoto (Department of Obstetrics and Gynecology, Nagoya University) to provide placental tissue. This work was supported in part by The Nakatomi Foundation, and by the Ministry of Education, Culture, Sports, Science and Technology of Japan [Grant-in-Aid 20591751 for Scientific Research (C)]

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Nagoya University Graduate School and School of Medicine, 65 Tsurumai, Showa-ku, Nagoya, Aichi, 466-8550, Japan

    Hiroshi Urakawa, Yoshihiro Nishida & Naoki Ishiguro

  2. Department of Orthopedic Surgery, Aichi Cancer Center Aichi Hospital, Okazaki, Japan

    Hiroatsu Nakashima

  3. Department of Pathology and Clinical Laboratories, Nagoya University Graduate School and School of Medicine, Nagoya, Japan

    Yoshie Shimoyama & Shigeo Nakamura

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  1. Hiroshi Urakawa
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  2. Yoshihiro Nishida
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  4. Yoshie Shimoyama
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Correspondence to Yoshihiro Nishida.

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Urakawa, H., Nishida, Y., Nakashima, H. et al. Prognostic value of indoleamine 2,3-dioxygenase expression in high grade osteosarcoma. Clin Exp Metastasis 26, 1005–1012 (2009). https://doi.org/10.1007/s10585-009-9290-7

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  • DOI: https://doi.org/10.1007/s10585-009-9290-7

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