P53 TUMOR-SUPPRESSOR PROTEIN OVEREXPRESSION IN OSTEOGENIC TUMORS OF DOGS

Alterations in the p53 tumor suppressor gene have been implicated in t he genesis and/or progression of the majority of human cancers, includ ing osteosarcoma. Stabilization of the protein by mutation or interact ion with other proteins prolongs its half-life, rendering it detectabl e by immunohistochemistry. Osteosarcoma is the most common primary can ine bone tumor and is characterized by frequent early metastases. Mult ilobular tumors of bone involve primarily flat bones of the head and a re low-grade malignancies with lower metastatic potential. The objecti ves of this study were to determine the prevalence of p53 protein over expression in 106 osteogenic tumors of dogs using an indirect immunohi stochemical method and to compare p53 overexpression between tumors wi th different clinical behavior. A polyclonal p53 antibody (CM-1) serve d as the primary antibody. Tumors were scored based upon an estimate o f the percentage of tumor cells stained. Significant differences in th e prevalence of overexpression were observed between osteosarcomas (72 %) and multilobular tumors of bone (20%, P = 0.0020). Osteosarcomas of the appendicular skeleton had a significantly higher prevalence of p5 3 overexpression (84%) than did osteosarcomas of the axial skeleton (5 6%, P = 0.0060). Our results show that p53 tumor suppressor protein is overexpressed in the majority of canine osteosarcomas. The higher pre valence of overexpression in osteosarcomas versus multilobular tumors of bone and in osteosarcomas of the appendicular skeleton versus those of the axial skeleton suggests that alterations in p53 expression cor relate with highly aggressive tumor behavior.