SATB2 Is a Novel Marker of Osteoblastic Differentiation in Bone and Soft Tissue Tumors
James R Conner, Jason L Hornick. Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Background: Special AT-rich sequence-binding protein 2 (SATB2) is a nuclear matrix protein that plays a critical role in osteoblast lineage commitment. Targeted knockout of Satb2 in mice results in impaired osteoblast differentiation and craniofacial skeletal defects. Similarly, germline deletions of the SATB2 locus are a rare cause of craniofacial malformations in humans. Identification of osteosarcomatous differentiation in bone and soft tissue tumors can pose a diagnostic challenge, as osteoid deposition is often limited in extent, and hyalinized collagenous stroma may closely mimic osteoid matrix. We investigated expression of SATB2 by immunohistochemistry (IHC) in osteosarcomas and other bone and soft tissue tumors to evaluate its potential diagnostic utility.
Design: Tissue sections of 61 tumors were evaluated: 27 osteosarcomas [20 of skeletal origin (15 primary tumors and 5 lung metastases), including 14 osteoblastic, 1 chondroblastic, 3 giant cell-rich, 1 parosteal, and 1 periosteal; and 7 extraskeletal], 2 osteoblastomas, 10 chondrosarcomas (5 dedifferentiated, 4 conventional, and 1 mesenchymal), 8 Ewing sarcomas (all confirmed to harbor EWSR1 rearrangements), 5 dedifferentiated liposarcomas with heterologous osteoblastic differentiation, 6 unclassified pleomorphic sarcomas, and 1 leiomyosarcoma. IHC was performed following pressure cooker antigen retrieval using a polyclonal anti-SATB2 antibody (1:250; Sigma).
Results: All 20 skeletal osteosarcomas, 6 of 7 extraskeletal osteosarcomas, and both osteoblastomas showed nuclear immunoreactivity for SATB2, usually of moderate-to-strong intensity, consistently in tumor cells adjacent to osteoid and more variably in cells not associated with matrix. Focal reactivity was also observed in 3 of 5 dedifferentiated chondrosarcomas, and in all 5 dedifferentiated liposarcomas, only in areas of heterologous osteosarcomatous differentiation. All other tumor types were completely negative for SATB2. Staining intensity was generally higher in small biopsies and lung metastases, compared to bone resection specimens, likely secondary to decalcification.
Conclusions: SATB2 is a specific marker of osteoblastic differentiation in mesenchymal tumors, both osteosarcomas and sarcomas with heterologous differentiation. Nuclear staining for SATB2 may be useful to distinguish osteosarcoma from histologic mimics and other osseous neoplasms.
Category: Bone & Soft Tissue
Tuesday, March 5, 2013 11:15 AM
Proffered Papers: Section G, Tuesday Morning