title: Cytoplasmic and/or nuclear accumulation of the beta-catenin protein is a frequent event in human osteosarcoma.
abstract: 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 beta-catenin signaling may play an important role in human tumorigenesis. To investigate the potential role of beta-catenin deregulation in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for beta-catenin accumulation using immunohistochemistry. Potential activating mutations were investigated by sequencing exon 3 of the beta-catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of beta-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 beta-catenin signaling in osteosarcoma. In our survival analysis, beta-catenin deregulation conferred a hazard ratio of 1.05, indicating that beta-catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinicopathologic parameters, beta-catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of beta-catenin signaling is a common occurrence in osteosarcoma that is implicated in the pathogenesis of osteosarcoma.
authors.affiliation: Molecular Oncology Laboratory, Department of Surgery, University of Chicago Medical Center, Chicago, IL 60637, USA.
authors.forename: Rex C
authors.initials: RC
authors.lastname: Haydon
authors.forename: Andrea
authors.initials: A
authors.lastname: Deyrup
authors.forename: Akira
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Robert
authors.initials: R
authors.lastname: Heck
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Lan
authors.initials: L
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.forename: David
authors.initials: D
authors.lastname: King
authors.forename: Hongwei
authors.initials: H
authors.lastname: Cheng
authors.forename: Benjamin
authors.initials: B
authors.lastname: Breyer
authors.forename: Terrance
authors.initials: T
authors.lastname: Peabody
authors.forename: Michael A
authors.initials: MA
authors.lastname: Simon
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Montag
authors.forename: Tong-Chuan
authors.initials: TC
authors.lastname: He
mesh_terms: D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009154:Mutation; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D015534:Trans-Activators; D051176:beta Catenin