Haitel A, Wiener H G, Baethge U, Marberger M, Susani M
Department of Pathology, University of Vienna, Austria.
Clin Cancer Res. 2000 May;6(5):1840-4.
The present study was designed to analyze the expression of p53 and mdm2 in clear cell renal cell carcinoma with special emphasis on their association with tumor grade and clinical outcome. In particular, the value of individual protein overexpression as well as combined p53/mdm2 positivity was evaluated because both proteins are functionally connected, and their expression is controlled by an autoregulatory feedback loop. A cohort of 97 clear cell renal cell carcinomas was analyzed. The overexpression of mdm2 and p53 proteins was investigated on paraffin-embedded material by using monoclonal antibodies. Eighteen tumors showed mdm2 positivity, whereas 35 of the tumors overexpressed p53. Whereas p53 and mdm2 positivity correlated significantly (P = 0.00004), no correlation could be found between mdm2 protein overexpression and tumor stage, lymph node involvement, and presence of distant metastases. mdm2 positivity was found significantly more frequently in tumors of higher grade. In univariate analysis, there was a statistically significant correlation between p53 and mdm2 overexpression in the same tumor and poor survival (P = 0.00179). Multivariate analysis revealed that coincident mdm2/p53 overexpression, the presence of distant metastases, and tumor grade were independent predictors for tumor progression. Our results indicate that mdm2/p53 co-overexpression, nuclear grade, and preoperative presence of distant metastasis are independent predictors for poor survival.
本研究旨在分析p53和mdm2在透明细胞肾细胞癌中的表达情况，特别关注它们与肿瘤分级和临床结局的关联。具体而言，对单个蛋白过表达以及p53/mdm2联合阳性的价值进行了评估，因为这两种蛋白在功能上相互关联，且它们的表达受一个自动调节反馈环控制。对97例透明细胞肾细胞癌队列进行了分析。通过使用单克隆抗体在石蜡包埋材料上研究mdm2和p53蛋白的过表达情况。18例肿瘤显示mdm2阳性，而35例肿瘤p53过表达。虽然p53和mdm2阳性显著相关（P = 0.00004），但未发现mdm2蛋白过表达与肿瘤分期、淋巴结受累及远处转移的存在之间存在相关性。在高级别肿瘤中，mdm2阳性的发现频率显著更高。在单变量分析中，同一肿瘤中p53和mdm2过表达与较差的生存率之间存在统计学显著相关性（P = 0.00179）。多变量分析显示，mdm2/p53同时过表达、远处转移的存在以及肿瘤分级是肿瘤进展的独立预测因素。我们的结果表明，mdm2/p53共同过表达、核分级以及术前远处转移的存在是生存率差的独立预测因素。
