Cytoplasmic and/or nuclear accumulation of the β-catenin protein is a frequent event in human osteosarcoma

Rex C. Haydon, Andrea Deyrup, Akira Ishikawa, Robert Heck, Wei Jiang, Lan Zhou, Tao Feng, David King, Hongwei Cheng, Benjamin Breyer, Terrance Peabody, Michael A. Simon, Anthony G. Montag, Tong Chuan He*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

159 Scopus citations


The molecular events that precede the development of osteosarcoma, the most common primary malignancy of bone, are unclear, and concurrent molecular and genetic alterations associated with its pathogenesis have yet to be identified. Recent studies suggest that activation of β-catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of β-catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for β-catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the β-catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of β-catenin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, suggesting that other regulatory mechanisms may play an important role in activating β-catenin signaling in osteosarcoma. In our survival analysis, β-catenin deregulation conferred a hazard ratio of 1.05, indicating that β-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, β-catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of β-catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.

Original languageEnglish (US)
Pages (from-to)338-342
Number of pages5
JournalInternational Journal of Cancer
Issue number4
StatePublished - Dec 1 2002


  • Bone tumor
  • Osteosarcoma
  • Tumorigenesis
  • Wnt signal
  • β-catenin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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