P53 PROTEIN ACCUMULATION AND GENETIC ALTERATIONS IN HUMAN GIANT-CELL TUMORS OF BONE (OSTEOCLASTOMAS)

Inactivation of tumor suppressor genes represents a critical determina nt in the development of a large proportion of human cancers. The tumo r suppressor gene p53 is the most frequently altered gene in human can cers. In the present study, p53 protein accumulation, gene mutation an d the association between p53 alteration and clinicopathological param eters was analyzed in 29 giant cell tumors of bone. p53 overexpression was detected by immunohistochemistry in 23 of 29 (79%) primary tumors but not in adjacent bone tissue. p53 gene mutations in exons 5-8 were detected in 15 of 29 (52%) of the tumors by polymerase chain reaction -single strand conformation polymorphism (PCR-SSCP) analysis. In 15 (5 2%) of 29 patient specimens, p53 immunostaining and mutations in exons 5-8 were concordant. Eleven (38%) of 29 tumors overexpressed p53 in t he absence of mutations in exons 5-8. No significant association betwe en p53 alterations and clinicopathological parameters was found. The p resent study represents the first report to assess p53 protein content and gene mutation in a substantial number of giant cell tumors of bon e and suggests that p53 alterations play an important role in the deve lopment of this neoplasm.