Runt-related transcription factor 2 (RUNX2) is a member of the Runx transcription factor family that regulates the differentiation of osteogenic and chondrogenic cells from mesenchymal precursors. RUNX2 is expressed in developing osteoblasts and progressively decreases during maturation. Overexpressing RUNX2 induces a high rate of bone turnover.

Of the Runx family members, RUNX1 and RUNX2 have been associated with oncogenesis. Aberrant function of RUNX2 has been implicated in oncogenesis and pathogenesis of some bone tumors including osteosarcoma and giant cell tumor. A large immunohistochemical study of 206 bone tumors revealed RUNX2 expression in the majority of osteoblastomas (90%, 19/21), osteoid osteomas (100%, 5/5), and osteosarcomas (93%, 66/71). Using an antibody panel containing RUNX2, TWIST1 and SOX9, giant cell tumors (RUNX2+, TWIST1-) and osteosarcoma (RUNX2+, TWIST1+) could be reliably differentiated from chondroblastoma and chondromyxoid fibroma (RUNX2-, SOX9+) with high sensitivity and specificity. Addition of RUNX2 immunohistochemistry may aid in the diagnosis of osteosarcoma.