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).


CONCLUSIONS
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.
Oliveira
Cláudia Regina Gomes Cardim Mendes de
CR
Department of Pathology, Orthopaedics and Traumatology Institute, Medical School, São Paulo University, São Paulo, SP, Brazil.
Mendonça
Berenice Bilharino
BB
Camargo
Olavo Pires de
OP
Pinto
Emilia Modolo
EM
Nascimento
Sérgio Antonio Barbosa
SA
Latorre
Maria do Rosario D O
Mdo R
Zerbini
Maria Claúdia Nogueira
MC
D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation / Q000235:genetics*; D018215:Osteoblastoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D012516:Osteosarcoma / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis* / Q000235:genetics; D012189:Retrospective Studies
D018809:Proliferating Cell Nuclear Antigen