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p53 mutations may be involved in malignant transformation of giant cell tumor of bone through interaction with GPX1

Virchows Archiv volume 463, pages 67–77 (2013)Cite this article

Abstract

Giant cell tumor of bone (GCTB) is a benign tumor with a tendency for local recurrence. Secondary malignant GCTB is rare, occurring in less than 2 % of GCTB cases. Mechanisms of malignant transformation of GCTB remain unclear. We examined 43 cases of GCTB (38 conventional cases, two lung implantation cases, and three secondary malignant cases) for p53 gene mutations and for loss of heterozygosity (LOH) of p53 when corresponding normal tissue was available. In addition, to elucidate the possible involvement of p53, GPX-1, cyclinD1, and Ki-67 in malignant transformation of GCTB, we assessed the expression of these proteins by immunohistochemistry. Mutations or LOH of p53 were found in all three malignant cases, which also showed p53 overexpression. Non-synonymous p53 mutations were detected in seven of 38 conventional cases (18 %), although none of these showed p53 overexpression, defined as more than 10 % of cells being positive. LOH at the p53 locus was detected in eight of 37 informative cases, although this was not associated with p53 overexpression in conventional GCT. Expression of GPX-1 was higher in the recurrent group, which included metastatic and malignant cases, and patients with high GPX-1 expression were at greater risk for early relapse. We also observed a positive correlation between high p53 expression and high GPX-1 expression in GCTB. Given that GPX-1 is shown to be a target of p53, these results suggest that p53 mutations play a role in tumor recurrence and malignant transformation of GCTB through interactions with GPX-1.

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Acknowledgments

We greatly appreciate the help of Keiko Mitani and Michiko Takahashi at the Department of Human Pathology, Juntendo University School of Medicine. This work was supported in part by a Grant-in-Aid for General Scientific Research from the Ministry of Education, Science, Sports and Culture (#23590434 to Tsuyoshi Saito and #24590429 to Hiroyuki Mitomi), Tokyo, Japan.

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  1. Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, Japan, 113-8421

    Taketo Okubo, Tsuyoshi Saito, Hiroyuki Mitomi & Takashi Yao

  2. Department of Orthopaedic Surgery, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, Japan, 113-8421

    Taketo Okubo, Tatsuya Takagi, Tomoaki Torigoe, Yoshiyuki Suehara & Kazuo Kaneko

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  1. Taketo Okubo
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  2. Tsuyoshi Saito
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  3. Hiroyuki Mitomi
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  4. Tatsuya Takagi
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Correspondence to Tsuyoshi Saito.

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Okubo, T., Saito, T., Mitomi, H. et al. p53 mutations may be involved in malignant transformation of giant cell tumor of bone through interaction with GPX1. Virchows Arch 463, 67–77 (2013). https://doi.org/10.1007/s00428-013-1435-z

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  • DOI: https://doi.org/10.1007/s00428-013-1435-z

Keywords

  • Giant cell tumor of bone
  • Malignant transformation
  • Mutation
  • p53
  • GPX-1