George Ben, Datar Ram H, Wu Lin, Cai Jie, Patten Nancy, Beil Stephen J, Groshen Susan, Stein John, Skinner Donald, Jones Peter A, Cote Richard J
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
J Clin Oncol. 2007 Dec 1;25(34):5352-8. doi: 10.1200/JCO.2006.10.4125.
The p53 gene status (mutation) and protein alterations (nuclear accumulation detectable by immunohistochemistry; p53 protein status) are associated with bladder cancer progression. Substantial discordance is documented between the p53 protein and gene status, yet no studies have examined the relationship between the gene-protein status and clinical outcome. This study evaluated the clinical relationship of the p53 gene and protein statuses.
The complete coding region of the p53 gene was queried using DNA from paraffin-embedded tissues and employing a p53 gene-sequencing chip. We compared p53 gene status, mutation site, and protein status with time to recurrence.
The p53 gene and protein statuses show significant concordance, yet 35% of cases showed discordance. Exon 5 mutations demonstrated a wild-type protein status in 18 of 22 samples. Both the p53 gene and protein statuses were significantly associated with stage and clinical outcome. Specific mutation sites were associated with clinical outcome; tumors with exon 5 mutations showed the same outcome as those with the wild-type gene. Combining the p53 gene and protein statuses stratifies patients into three distinct groups, based on recurrence-free intervals: patients showing the best outcome (wild-type gene and unaltered protein), an intermediate outcome (either a mutated gene or an altered protein) and the worst outcome (a mutated gene and an altered protein).
We show that evaluation of both the p53 gene and protein statuses provides information in assessing the clinical recurrence risk in bladder cancer and that the specific mutation site may be important in assessing recurrence risk. These findings may substantially impact the assessment of p53 alterations and the management of bladder cancer.
p53基因状态（突变）和蛋白改变（免疫组织化学可检测到的核积聚；p53蛋白状态）与膀胱癌进展相关。p53蛋白和基因状态之间存在显著不一致，但尚无研究探讨基因-蛋白状态与临床结局之间的关系。本研究评估了p53基因和蛋白状态的临床关系。
使用石蜡包埋组织的DNA并采用p53基因测序芯片查询p53基因的完整编码区。我们将p53基因状态、突变位点和蛋白状态与复发时间进行了比较。
p53基因和蛋白状态显示出显著一致性，但35%的病例显示不一致。22个样本中有18个样本的外显子5突变表现为野生型蛋白状态。p53基因和蛋白状态均与分期和临床结局显著相关。特定的突变位点与临床结局相关；外显子5突变的肿瘤与野生型基因的肿瘤表现出相同的结局。根据无复发生存期，将p53基因和蛋白状态相结合可将患者分为三个不同的组：预后最佳的患者（野生型基因且蛋白未改变）、中等预后的患者（基因或蛋白发生改变）和预后最差的患者（基因和蛋白均发生改变）。
我们表明，评估p53基因和蛋白状态可为评估膀胱癌的临床复发风险提供信息，且特定的突变位点在评估复发风险中可能很重要。这些发现可能会对p53改变的评估和膀胱癌的管理产生重大影响。
