p63 contributes to skeletal development and
tumor formation; however, little is known regarding its activity in the context of bone and
soft tissue neoplasms. The purpose of this study was to investigate p63 expression in
giant cell tumor of bone and to determine whether it can be used to discriminate between other giant cell-rich
tumors. Seventeen cases of
giant cell tumor of bone were examined to determine the cell type expressing p63 and identify the
isoforms present. Total
RNA or cell
protein was extracted from mononuclear- or giant cell-enriched fractions or intact
giant cell tumor of bone and examined by RT-PCR or western blot, respectively. Immunohistochemistry was used to evaluate p63 expression in
paraffin embedded sections of
giant cell tumor of bone and in
tumors containing multinucleated giant cells, including:
giant cell tumor of tendon sheath,
pigmented villonodular synovitis, aneurysmal
bone cyst,
chondroblastoma, and central
giant cell granuloma. The mononuclear cell component in all cases of
giant cell tumor of bone was found to express all forms of TAp63 (alpha, beta, and gamma), whereas only low levels of the TAp63 alpha and beta
isoforms were detected in multinucleated cells; DeltaNp63 was not detected in these
tumors. Western blot analysis identified p63
protein as being predominately localized to mononuclear cells compared to giant cells. This was confirmed by immunohistochemical staining of
paraffin-embedded
tumor sections, with expression identified in all cases of
giant cell tumor of bone. Only a proportion of cases of aneurysmal
bone cyst and
chondroblastoma showed p63 immunoreactivity whereas it was not detected in central
giant cell granuloma,
giant cell tumor of tendon sheath, or
pigmented villonodular synovitis. The differential expression of p63 in
giant cell tumor of bone and central
giant cell granuloma suggest that these two
tumors may have a different pathogenesis. Moreover, p63 may be a useful
biomarker to differentiate
giant cell tumor of bone from central
giant cell granuloma and other giant cell-rich
tumors, such as
giant cell tumor of tendon sheath and
pigmented villonodular synovitis.