Nuclear beta-catenin correlates with cyclin D1 expression in spindle and pleomorphic sarcomas but not in synovial...

Nuclear beta-catenin staining in soft tissue sarcomas (STSs) has been shown to correlate with tumor progression as assessed by proliferative activity or poor prognosis. Frequent activation of Wnt signaling pathway has been also shown in synovial sarcoma (SS), suggesting a specific role of this pathway in SS. We examined roles of nuclear beta-catenin staining within soft tissue sarcomas. Immunohistochemical detection of nuclear beta-catenin accumulation correlated with cyclin D1 overexpression in spindle cell and pleomorphic sarcomas (P = .037), and the expression of these proteins evenly distributed throughout each section. In some cases, strong beta-catenin nuclear staining was observed in highly pleomorphic and mitotic cells. Furthermore, tumors with nuclear beta-catenin accumulation showed statistically significant increasing cyclin D1 mRNA expression level compared with those without (P = .023). Cyclin D1 mRNA expression levels were statistically higher in tumors with cyclin D1 overexpression than in tumors without (P = .037), suggesting that cyclin D1 overexpression is due to transcriptional activation. However, these correlations could not be detected in SS. In biphasic SS, beta-catenin nuclear staining was observed in spindle cells, whereas cyclin D1 nuclear staining was seen in glandular areas where beta-catenin kept membranous expression. Mutations in exon 3 of the beta-catenin gene and in the mutation cluster region of adenomatous polyposis coli gene were absent in this series of cases. Thus, cyclin D1 could be considered as one of the targets of the nuclear beta-catenin in spindle cell and pleomorphic sarcomas. A possible association between beta-catenin accumulation and spindle cell morphogenesis may exist in SS.