Nuclear beta-catenin in mesenchymal tumors

摘要

-Catenin is a crucial part of the Wnt and E-cadherin signalling pathways, which are involved in tumorigenesis. Dysregulation of these pathways allow -catenin to accumulate and translocate to the nucleus, where it may activate oncogenes. Such nuclear accumulation can be detected by immunohistochemistry, which may be useful in diagnosis. Although the role of -catenin has been established in various types of carcinomas, relatively little is known about its status in mesenchymal tumors. A number of studies suggest that -catenin dysregulation is important in desmoid-type fibromatosis, as well as in synovial sarcoma. We wished to determine whether nuclear -catenin expression is specific to and sensitive for particular bone and soft-tissue tumors, including sporadic desmoid-type fibromatosis. We studied the nuclear expression of -catenin using tissue microarrays in a comprehensive range of bone and soft-tissue tumor types. A total of 549 cases were included in our panel. Nuclear immunohistochemical staining was determined to be either high level (>25% of cells), low level (0–25%) or none. High-level nuclear -catenin staining was seen in a very limited subset of tumor types, including desmoid-type fibromatosis (71% of cases), solitary fibrous tumor (40%), endometrial stromal sarcoma (40%) and synovial sarcoma (28%). Although occasional cases of fibrosarcoma, clear cell sarcoma and carcinosarcoma had high-level staining, no high-level nuclear -catenin expression was seen in any of 381 fibrohistocytic, muscular, adipocytic, chondroid or osseous tumor cases representing 42 diagnostic categories. All primary immunostain tissue microarray images are made publicly accessible in a searchable database. High-level nuclear -catenin staining serves as a useful diagnostic tool, as it is specific to a small subset of mesenchymal tumors.