Tissue microarray validation of epidermal growth factor receptor and SALL2 in synovial sarcoma with comparison to tumors of similar histology

Abstract

Histological diagnosis of synovial sarcoma can be difficult. Genome-wide expression profiling has identified a number of genes expressed at higher levels in synovial sarcoma than in other soft tissue tumors, representing excellent candidates for diagnostic immunohistochemical markers. A tissue microarray comprising 77 sarcomas, including 46 synovial sarcomas, was constructed to validate identified markers and investigate their expression in tumors in the differential diagnosis of synovial sarcoma. Immunostaining was performed for two such markers, epidermal growth factor receptor and SAL (drosophila)-like 2 (SALL2), and for fifteen established markers used in the differential diagnosis of sarcomas. As predicted by expression profiling, epidermal growth factor receptor (a potential therapeutic target) and SALL2 stained most cases of synovial sarcoma; staining was significantly less common among other tested sarcomas. Hierarchical clustering analysis applied to immunostaining results for all 18 antibodies showed that synovial sarcomas, leiomyosarcomas, hemangiopericytomas, and solitary fibrous tumors cluster distinctly, and assigned one case with indeterminate histology as a Ewing sarcoma. Digital images from over 2500 immunostained cores analyzed in this study were captured and are made accessible through the accompanying website: http://microarray-pubs.stanford.edu/tma_portal/synsarc.

Figure 1.

A: Strong, predominantly membranous EGFR immunostaining of a monophasic synovial sarcoma (original magnification, ×400). B: Nuclear immunostaining of synovial sarcoma by SALL2 (original magnification, ×600).

Figure 2.

Hierarchical cluster analysis of synovial sarcoma tissue microarray immunostaining results. For each of the antibodies indicated at the top of the figure, strong positive staining is indicated by a red square, weak positive by brown, absence of staining as green, and no available data as white. The dendrogram at the top shows the clustering of the antibodies based on the relatedness of tumors stained by each antibody. Individual case details are listed at the right; the dendrogram at the left shows the clustering of the tumors based on the degree of similarity of their immunohistochemical staining results.