Classical osteoblastoma, atypical osteoblastoma, and osteosarcoma: a comparative study based on clinical, histological, and biological parameters.

OBJECTIVE: To investigate the biological behavior of classical and atypical osteoblastomas in comparison to osteosarcomas.

METHODS: Based on histological parameters, 30 osteoblastomas were subclassified as classical osteoblastomas (23/30) or atypical osteoblastoma (high cellularity, prominent blue osteoid, and epithelioid osteoblasts--7/30). Comparative immunohistochemical and clinical analysis was performed in 17 cases of patients with high-grade osteosarcoma. Formalin-fixed, paraffin-embedded archival tissue was immunostained for p53 and proliferation cell nuclear antigen. Tumors with positive p53 stain underwent molecular analyses for fragments of exon 10.

RESULTS: The mean proliferating cell nuclear antigen indexes for classical osteoblastoma, atypical osteoblastoma, and osteosarcoma were 33%, 61%, and 79%, respectively. The atypical subgroup showed similar results to those of the osteosarcoma group (P < 0.001). p53 protein was detected in 4 (13%) osteoblastomas (3 of these were atypical osteoblastoma), and 4 osteosarcomas (23%) also showed p53 positivity. DNA mutation performed in p53-positive cases was confirmed in exon 10 in 2 atypical osteoblastomas (2/3), 1 classical osteoblastoma (1/1), and 1 osteosarcoma (1/4). Disease recurrence was correlated with p53 expression (P = 0.009), atypical subtype (P = 0.031), spiculated blue bone on histology (P = 0.018), and proliferating-cell nuclear antigen labeling index > or =40 (P = 0.015).

CONCLUSION: These results validate atypical osteoblastoma as an entity, with p53 and proliferation cell nuclear antigen immuno-expression closer to that of osteosarcoma than of classical osteoblastoma. Proliferating cell nuclear antigen labeling index and p53 may be useful predictors of recurrence.