P53 Expression as a Prognostic Marker in Giant Cell Tumor of Bone: A Pilot Study

Abstract

P53 is the best known tumor suppressor gene. If p53 is mutated, the ability of the cell to sense and repair DNA defects is lost. Failure of this mechanism increases the risk of malignant transformation and tumorigenesis. P53 overexpression is implicated in many carcinomas. P53 alterations appear to be frequent in bone and soft tissue sarcoma and have a strong negative impact on survival in various subtypes of sarcoma like Ewing's sarcoma, synovial sarcoma, and myxoid liposarcoma. There is also evidence in the literature that p53 may be implicated in bone giant cell tumor behavior. The goal of this pilot retrospective study was to detect p53 mutation in giant cell tumor of bone and correlate it with clinical outcome. We analyzed the presence of p53 mutation in 39 patients with giant cell tumor of bone by means of immunohistochemical staining; 8 tumors expressed mutated p53 protein. Seven of them recurred locally (P<.001) and 2 metastasized to the lung (P<.05). In multivariate analysis/subgroup analysis, local recurrence was still strongly correlated, while metastasis had a weaker correlation. Our findings suggest that p53 mutation in giant cell tumor of bone can be useful in predicting tumor behavior, especially in regard to local recurrence. Limitations of this study include the retrospective data collection, the limited number of patients, and the multifactorial nature of the disease; tumor grade, surgical margins, use of adjuvant therapy, and thoroughness of excision may influence the therapeutic outcome. Despite these limitations, this correlation should be further investigated with larger clinical studies. P53 may be used as a marker for the biologic behavior of giant cell tumor of bone.