β-Catenin Nuclear Expression Correlates With Cyclin D1 Expression in Primary and Metastatic Synovial Sarcoma: A Tissue Microarray Study

Abstract

Abstract Context.—The association between aberrant (nuclear) β-catenin expression and cyclin D1 accumulation has been demonstrated in diverse neoplasms. In synovial sarcoma (SS), aberrant β-catenin expression has prognostic relevance, but the association with cyclin D1 has not been established. The SYT-SSX fusion protein, unique to SS, may independently increase cyclin D1. Objective.—To determine whether nuclear β-catenin is associated with cyclin D1 overexpression in SS and whether primary and metastatic SS differ in the expression of these markers. Design.—We incorporated 82 tumors initially diagnosed as SS into a tissue array. Fluorescence in situ hybridization with custom probes was used to select t(X;18) positive tumors. Clinical data, tumor type and outcome were tabulated. The tumors were tested for the association between nuclear β-catenin and cyclin D1 immunostaining. Primary and metastatic tumors were compared. Results.—Fifty-one tumors (41 primary and 10 metastatic) from 43 patients demonstrated t(X;18). Cyclin D1 staining was identified in 21 (59%) primary and 8 (80%) metastatic tumors, respectively, and nuclear β-catenin in 24 (41%) primary and 7 (70%) metastatic tumors, respectively. No significant difference was noted between primary and metastatic tumors with respect to the above markers. The presence of nuclear β-catenin showed a significant association with cyclin D1 expression (P < .001). A small number of cyclin D1 cases were negative for nuclear β-catenin but positive for phosphorylated Akt. Conclusions.—Increased cyclin D1 in SS may be driven by abnormally expressed β-catenin, similar to other neoplasms. The pattern of expression of these markers is established early during tumorigenesis.