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Cytoplasmic and/or nuclear accumulation of the β‐catenin protein is a frequent event in human osteosarcoma
Author(s) -
Haydon Rex C.,
Deyrup Andrea,
Ishikawa Akira,
Heck Robert,
Jiang Wei,
Zhou Lan,
Feng Tao,
King David,
Cheng Hongwei,
Breyer Benjamin,
Peabody Terrance,
Simon Michael A.,
Montag Anthony G.,
He TongChuan
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10719
Subject(s) - osteosarcoma , carcinogenesis , catenin , pathogenesis , biology , cancer research , mutation , exon , pathology , signal transduction , gene , genetics , wnt signaling pathway , medicine , immunology
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. © 2002 Wiley‐Liss, Inc.