CYTOPLASMIC AND/OR NUCLEAR ACCUMULATION OF THE -CATENIN PROTEIN IS A FREQUENT EVENT IN HUMAN OSTEOSARCOMA

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 -catenin signaling may play an important role in human tumorigene-sis. To investigate the potential role of -catenin deregula-tion in human osteosarcoma, we analyzed a panel of 47 osteosarcoma samples for -catenin accumulation using im-munohistochemistry. Potential activating mutations were in-vestigated by sequencing exon 3 of the -catenin gene in genomic DNA isolated from tumor samples. Our findings revealed cytoplasmic and/or nuclear accumulation of -cate-nin in 33 of 47 samples (70.2%); however, mutation analysis failed to detect any genetic alterations within exon 3, sug-gesting that other regulatory mechanisms may play an im-portant role in activating -catenin signaling in osteosar-coma. In our survival analysis, -catenin deregulation conferred a hazard ratio of 1.05, indicating that -catenin accumulation does not appear to be of prognostic value for osteosarcoma patients. When analyzed against other clinico-pathologic parameters, -catenin accumulation correlated only with younger age at presentation (26.4 vs. 39.8 years). Nevertheless, our results demonstrate that the deregulation of -catenin signaling is a common occurrence in osteosar-coma that is implicated in the pathogenesis of osteosarcoma