Lonardo F, Ueda T, Huvos A G, Healey J, Ladanyi M
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer. 1997 Apr 15;79(8):1541-7.
Alterations of the p53 gene and of MDM2, a gene coding for a p53 binding protein, have been implicated in the pathogenesis of osteosarcoma (OS).
To determine the frequency of alterations of the p53/MDM2 pathway in OS and their possible correlation with clinicopathologic features, MDM2 copy number and p53 protein levels were determined in a series of 83 samples of OS by quantitative Southern blot analysis and immunohistochemistry, respectively.
Positivity for p53 was found in 26.5% and MDM2 amplification in 6.6% of the samples analyzed in a mutually exclusive fashion with one exception. Overall, alterations of the p53/MDM2 pathway occurred in 34% of cases; p53 accumulation was not associated with a higher proliferative rate. The mean age of patients with p53 positive OS (40 years) was older than that of the p53 negative group (28 years) (P < 0.04). Furthermore, three of the four cases of OS arising in Paget's disease showed p53 accumulation.
Alterations of the p53/MDM2 pathway are frequent in OS and usually represent mutually exclusive tumorigenic events. p53 does not appear to be a major determinant of proliferative rate in OS.
p53基因以及编码p53结合蛋白的MDM2基因的改变与骨肉瘤（OS）的发病机制有关。
为了确定OS中p53/MDM2通路改变的频率及其与临床病理特征的可能相关性，分别通过定量Southern印迹分析和免疫组织化学方法，对83例OS样本中的MDM2拷贝数和p53蛋白水平进行了检测。
在所分析的样本中，p53阳性率为26.5%，MDM2扩增率为6.6%，二者呈相互排斥的关系，仅有1例例外。总体而言，34%的病例出现了p53/MDM2通路的改变；p53积聚与较高的增殖率无关。p53阳性OS患者的平均年龄（40岁）高于p53阴性组（28岁）（P < 0.04）。此外，在佩吉特病基础上发生的4例OS中有3例显示p53积聚。
p53/MDM2通路改变在OS中很常见，通常代表相互排斥的致瘤事件。p53似乎不是OS增殖率的主要决定因素。
