Immunohistochemical investigation of cell cycle and apoptosis regulators (survivin, β-catenin, p53, caspase 3) in canine appendicular osteosarcoma.
BACKGROUND
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).


RESULTS
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).


CONCLUSIONS
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.
Department of Comparative Biomedical Sciences, Faculty of Veterinary Medicine, University of Teramo, piazza Aldo Moro, 45, 64100, Teramo, Italy.
Laura
L
Bongiovanni
Francesca
F
Mazzocchetti
Daniela
D
Malatesta
Mariarita
M
Romanucci
Andrea
A
Ciccarelli
Paolo
P
Buracco
Raffaella
R
De Maria
Chiara
C
Palmieri
Marina
M
Martano
Emanuela
E
Morello
Lorella
L
Maniscalco
Leonardo
L
Della Salda
D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D004283:Dog Diseases / Q000378:metabolism*; D004285:Dogs; D005121:Extremities / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D012516:Osteosarcoma / Q000378:metabolism / Q000662:veterinary*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D051034:Inhibitor of Apoptosis Proteins; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D053148:Caspase 3