Open Access Highly Accessed Research article

Immunohistochemical investigation of cell cycle and apoptosis regulators (Survivin, β-Catenin, P53, Caspase 3) in canine appendicular osteosarcoma

Laura Bongiovanni1, Francesca Mazzocchetti1, Daniela Malatesta1, Mariarita Romanucci1, Andrea Ciccarelli2, Paolo Buracco3, Raffaella De Maria3, Chiara Palmieri1, Marina Martano3, Emanuela Morello3, Lorella Maniscalco3 and Leonardo Della Salda1*

Author Affiliations

1 Department of Comparative Biomedical Sciences, Faculty of Veterinary Medicine, University of Teramo, piazza Aldo Moro, 45, 64100, Teramo, Italy

2 Department of Communication Sciences, University of Teramo, Campus Coste Sant’Agostino, 64100, Teramo, Italy

3 Department of Animal Pathology, Faculty of Veterinary Medicine, University of Torino, via L. Da Vinci 48, 10095, Grugliasco, TO, Italy

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BMC Veterinary Research 2012, 8:78  doi:10.1186/1746-6148-8-78

Published: 11 June 2012



Osteosarcoma (OSA) represents the most common canine primary bone tumour. Despite several pathways have been investigated so far, few molecules have been identified as prognostic tools or potential therapeutic targets, and there is still the need to find out molecular pathways with specific influence over OSA progression to facilitate earlier prognosis and treatment.

Aims of the present study were to evaluate the immunohistochemical pattern and levels of expression of a panel of molecules (survivin, β-catenin, caspase 3 -inactive and active forms- and p53) involved in cell cycle and apoptosis regulation in canine OSA samples, known to be of interest in the study also of human OSA, and to detect specific relations among them and with histological tumour grade, disease free interval (DFI) and overall survival (OS).


Nuclear β-catenin immunostaining was detected in normal osteoblasts adjacent to the tumour, and in 47% of the cases. Cytoplasmic and/or membranous immunostaining were also observed. Nuclear survivin and p53 positive cells were found in all cases. Moderate/high cytoplasmic β-catenin expression (≥10% positive cells) was significantly associated with the development of metastasis (P = 0.014); moderate/high nuclear p53 expression (≥10% positive cells) was significantly associated with moderate/high histological grade (P = 0.017) and shorter OS (P = 0.049). Moderate/high nuclear survivin expression (≥15% positive cells) showed a tendency toward a longer OS (P = 0,088).


The present results confirmed p53 as negative prognostic marker, while suggested survivin as a potential positive prognostic indicator, rather than indicative of a poor prognosis. The detection of nuclear β-catenin immunostaining in normal osteoblasts and the absent/low expression in most of the OSAs, suggested that this pathway could not play a major role in oncogenic transformation of canine osteoblasts. Further studies are needed to confirm these hypotheses.