Special AT-rich sequence-binding protein 2 (SATB2) expression is sensitive but may not be specific for osteosarcoma as compared with other high-grade primary bone sarcomas

Aims: The diagnosis of osteosarcoma, although important for eligibility in clinical trials and proper therapy, may be challenging when no bone or osteoid matrix is identified on biopsy. Therefore, other adjunct tests have been sought to help confirm the diagnosis. Special AT-rich sequence-binding protein 2 (SATB2) has been shown as a reliable marker of osteoblastic differentiation. The aim of this study was to examine SATB2 expression in osteosarcomas and other primary bone sarcomas, in order to evaluate its diagnostic utility in discriminating osteogenic from non-osteogenic sarcomas. Methods and results: Forty-eight pretreated osteosarcoma biopsies, including 26 whole-section cases and 22 tumours on tissue microarrays, and 36 non-osteogenic bone sarcomas were evaluated. Forty-five of 48 (94%) osteosarcomas showed nuclear immunoreactivity for SATB2 (all whole-slide sections showed expression). Positive SATB2 expression was observed in 11 of 22 (50%) undifferentiated pleomorphic sarcomas (UPSs), and in five of 11 (45%) fibrosarcomas; expression was absent in two pleomorphic rhabdomyosarcomas and in the one leiomyosarcoma. The sensitivity of SATB2 for osteosarcoma was 94%, and the specificity was 55%. Stronger-intensity staining was observed in osteosarcoma (P < 0.0001). Conclusions: SATB2 is a sensitive marker for osteosarcoma; however, it is not specific, with expression being observed in other high-grade primary bone sarcomas. Intriguingly, the lack of specificity may suggest that the undifferentiated sarcomas (UPSs and fibrosarcomas) with SATB2 expression actually represent osteosarcomas that produce too little matrix to be detected with routine sampling or consist of osteoblast precursors that do not synthesize matrix.