p53 Tumor Suppressor Protein Overexpression in Osteogenic Tumors of Dogs

Abstract

Abstract. Alterations in the p53 tumor suppressor gene have been implicated in the genesis and/or progression of the majority of human cancers, including osteosarcoma. Stabilization of the protein by mutation or interaction with other proteins prolongs its half-life, rendering it detectable by immunohistochemistry. Osteosarcoma is the most common primary canine bone tumor and is characterized by frequent early metastases. Multilobular tumors of bone involve primarily flat bones of the head and are low-grade malignancies with lower metastatic potential. The objectives of this study were to determine the prevalence of p53 protein overexpression in 106 osteogenic tumors of dogs using an indirect immunohistochemical method and to compare p53 overexpression between tumors with different clinical behavior. A polyclonal p53 antibody (CM-1) served as the primary antibody. Tumors were scored based upon an estimate of the percentage of tumor cells stained. Significant differences in the prevalence of overexpression were observed between osteosarcomas (72%) and multilobular tumors of bone (20Y0, P = 0.0020). Osteosarcomas of the appendicular skeleton had a significantly higher prevalence of p53 overexpression (84%) than did osteosarcomas of the axial skeleton (56Y0, P = 0.0060). Our results show that p53 tumor suppressor protein is overexpressed in the majority of canine osteosarcomas. The higher prevalence 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 correlate with highly aggressive tumor behavior.

Isolation of canine p53 cDNA and detailed characterization of the full length canine p53 protein

“…Immunoreactivity of the canine p53 protein towards CM-1 rabbit anti-human p53 polyclonal antibody (Sagartz et al, 1996;Gamblin et al, 1997;Wolf et al, 1997) and to the monoclonal PAb240 antibody (Teifke and Lohr, 1996) has been shown in immunohistochemical analyses of canine neoplasms. In order to further de®ne the immunoreactivity of canine p53, we used a panel of monoclonal antibodies in an immunoprecipitation assay (Figure 3b).…”

“…Recently similar mutations within the canine p53 gene have been identi®ed in a small number of canine cancer types including: thyroid carcinoma (Devilee et al, 1994), oral papilloma (Mayr et al, 1994), mammary tumours (Van Leeuwen et al, 1996), osteosarcoma (Van Leeuwen et al, 1997), circumanal gland adenoma (Mayr et al, 1997) and lymphoma (Veldhoen et al, 1998). Overexpression of the canine p53 protein was also observed in tumours of epithelial, mesenchymal and round cell origins (Sagartz et al, 1996;Gamblin et al, 1997;Wolf et al, 1997). The vast clinical knowledge concerning the identi®cation and treatment of canine cancers and the apparent similarity of p53 inactivation in the tumours of some cancer patients identi®es canine p53 as a potential target for anti-cancer therapy in the dog.…”

Clinicopathologic Significance of Histologic Grade, Pgp, and P53 Expression in Canine Lymphoma

“…The p53 gene is reportedly mutated in the majority of human and canine cancers. [16][17][18][19][20][21][22][23][24][25][26] Mutations of the p53 gene are associated with a number of canine lymphoid and nonlymphoid cancers such as osteosarcoma, LSA, and various carcinomas.…”

Detection of mutations within exons 4 to 8 of the p53 tumor suppressor gene in canine mammary glands

“…Overexpression of the mutant p53 protein has also been observed in canine tumors of epithelial, mesenchymal and round cell origins (Sagartz et al, 1996, Wolf et al, 1997. The expression of p53 assessed by real-time polymerase chain reaction (PCR), however, may be heterogeneous in mammary tumors such as adenoma, adenosarcoma and their metastasis in lymphnodes (Klopfleisch and Gruber, 2009).…”