Journal
CANCER
Volume 107, Issue 3, Pages 554-562Publisher
WILEY
DOI: 10.1002/cncr.22019
Keywords
osteosarcoma; jaw neoplasms; bone neoplasms; radiotherapy; protein p53, p53 gene, Ki-67 antigen; MIB-1 antibody; ezrin
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BACKGROUND. Craniofacial osteosarcoma differs from long bone osteosarcoma in that patients are older, tumors are often low grade, and prognosis is more favorable. Although most are sporadic, some tumors occur in association with prior radiation therapy. The purpose of the current study was to compare clinicopathologic and prognostic features of primary and radiation-associated osteosarcoma. METHODS. The study group consisted of 15 primary and 6 radiation-associated osteosarcomas. Clinical and follow-up data were obtained in every case. Tissue microarrays were immunohistochemically stained for p53, pRB, Ki-67 (MIB-1), and ezrin. DNA was sequenced for TP53 mutations. RESULTS. All radiation-associated osteosarcomas were high grade and half were fibroblastic. In contrast, 47% of primary craniofacial osteosarcomas were high grade and only 1 was fibroblastic. All radiation-associated osteosarcomas recurred, half the patients died of disease, 2 were alive with unresectable tumors, whereas only I was alive without disease. In contrast, 80% of patients with primary tumors were alive without disease, 33% had local recurrences, and 13% died of disease. Radiation-associated tumors overexpressed p53 more often (33% vs. 13%), more often had TP53 mutations (33% vs. 8%), had higher proliferative activity (67% vs. 0% showing > 50% MIB-1 staining), and expressed ezrin more frequently (83% vs. 40%) than primary tumors. Compared with a control group of 24 high- and 7 low-grade primary extremity osteosarcomas, radiation-associated tumors marked as the high-grade tumors. CONCLUSIONS. Craniofacial radiation-associated osteosarcomas are high-grade tumors that behave more aggressively than most primary craniofacial osteosarcomas. In addition, they demonstrate higher expression rates of adverse prognostic indicators, further highlighting the distinction.
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