Department of Comparative Biomedical Sciences, Faculty of Veterinary Medicine, University of Teramo, piazza Aldo Moro, 45, 64100, Teramo, Italy.
BMC Vet Res. 2012 Jun 11;8:78. doi: 10.1186/1746-6148-8-78.
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.
骨肉瘤（OSA）是犬类最常见的原发性骨肿瘤。尽管目前已经研究了几种途径，但只有少数分子被确定为预后工具或潜在的治疗靶点，因此仍需要发现对 OSA 进展有特定影响的分子途径，以促进更早的预后和治疗。本研究的目的是评估细胞周期和凋亡调节相关分子（存活素、β-连环蛋白、无活性和活性形式的半胱天冬酶 3 以及 p53）在犬骨肉瘤样本中的免疫组织化学表达模式和水平，这些分子在骨肉瘤的研究中也很重要，同时还检测了它们之间与组织学肿瘤分级、无病间隔（DFI）和总生存（OS）之间的特定关系。
在肿瘤旁的正常成骨细胞中检测到核β-连环蛋白免疫染色，在 47%的病例中观察到细胞质和/或膜免疫染色。所有病例均发现核存活素和 p53 阳性细胞。中等/高细胞质β-连环蛋白表达（≥10%阳性细胞）与转移的发生显著相关（P=0.014）；中等/高核 p53 表达（≥10%阳性细胞）与中等/高组织学分级（P=0.017）和较短的 OS（P=0.049）显著相关。中等/高核存活素表达（≥15%阳性细胞）显示出较长 OS 的趋势（P=0.088）。
本研究结果证实了 p53 作为负预后标志物，而提示存活素可能是一个潜在的正预后指标，而不是预后不良的指标。在正常成骨细胞中检测到核β-连环蛋白免疫染色，而在大多数 OSA 中检测到核β-连环蛋白缺失/低表达，表明该途径在犬类成骨细胞的致癌转化中可能不起主要作用。需要进一步的研究来证实这些假设。
