1. ¹Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada
2. ²University Musculoskeletal Oncology Unit, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
3. ³Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, MA, USA
4. ⁴Division of Orthopaedic Surgery, The Ottawa Hospital, Ottawa, ON, Canada
5. ⁵Department of Orthopedic Surgery, McGill University Health Centre, Montreal, QC, Canada

Correspondence: Dr RA Kandel, MD, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Room 6-500, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5. E-mail: rkandel@mtsinai.on.ca

^*Current address: Department of Oral Medicine, Infection & Immunity, Harvard School of Dental Medicine, Boston, MA, USA

Received 6 March 2007; Revised 26 April 2007; Accepted 7 May 2007; Published online 29 February 2008.

Abstract

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 (, , and ), whereas only low levels of the TAp63 and isoforms were detected in multinucleated cells; Np63 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.