Genetic and immunophenotype analyses of TP53 in bladder cancer -: TP53 alterations are associated with tumor progression
Genetic and immunophenotype analyses of TP53 in bladder cancer -: TP53 alterations are associated with tumor progression
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DOI：
10.1097/01.pdm.0000137098.03878.00
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发表时间：
2004-12-01
影响因子：
--
通讯作者：
Puig, X
中科院分区：
文献类型：
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作者：
Erill, N;Colomer, A;Puig, X
p53状态改变是膀胱癌中的常见事件，据报道具有预后意义。我们研究了76例膀胱癌患者的TP 53基因及其产物，采用免疫组织化学（单克隆抗体DO-7），聚合酶链反应单链构象多态性（外显子4-8），然后直接测序的移动带，并在17 p（p53 CA）杂合性丢失。还研究了H-RAS突变。应用受试者工作特征曲线和Logistic回归分析评价免疫组化预测TP 53突变的有效性。一个p53阳性的核表型被定义为截止20%的肿瘤细胞的免疫反应性，并发现在23例，而TP 53突变检测22例，其中4例为阴性p53表型。在23例病例中发现TP 53缺失。未观察到H-RAS基因突变。表型和基因型结果之间有显着关联。此外，观察到p53状态与肿瘤分期和级别之间存在显着相关性，这种变化在高分期和高级别肿瘤中更常见（均为X-2检验; P < .01）。17 p缺失与肿瘤分期（P <0.01）和分级（P = 0.01）显著相关，等位基因丢失在晚期疾病中更常见。来自这些研究的数据表明，遗传分析是必要的最佳确定TP 53的变化，主要是在肿瘤与p53阴性表型，特别是在早期肿瘤的p53状态可能有助于确定其进展为浸润性疾病。由于p53改变与预后不良的临床病理特征显著相关，因此建议将p53表型和TP 53突变状态纳入膀胱癌肿瘤标志物的预测组中。
Altered p53 status is a frequent event in bladder cancer and reported to have prognostic significance. We studied the TP53 gene and its product in 76 patients affected with urinary bladder carcinomas by immunohistochemistry (mAb DO-7), polymerase chain reaction single-strand conformational polymorphism (exons 4-8) followed by direct sequencing of shifted bands, and loss of heterozygosity in 17p (p53CA). H-RAS mutations were also studied. The receiver operating characteristic curve and the logistic-regression analysis were used to evaluate the validity of immunohistochemistry in predicting TP53 mutations. A p53-positive nuclear phenotype was defined by a cutoff of 20% tumor cells being immunoreactive and was found in 23 cases, while TP53 mutations were detected in 22 cases, four of them with a negative p53 phenotype. TP53 deletions were identified in 23 cases. No H-RAS gene mutations were observed. There was a significant association between phenotype and genotype results. Moreover, a significant association was observed between p53 status and tumor stage and grade, being alterations more common in high-stage and high-grade tumors (both X-2 test; P < .01). Deletion of 17p significantly correlated with tumor stage (P < .01) and grade (P = .01), allelic losses being more common in advanced disease. Data from these studies suggest that genetic assays are necessary for the optimal determination of TP53 alterations, mainly in tumors with a p53 negative phenotype, and especially in early stage tumors for which p53 status may assist in determining its progression to invasive disease. Since p53 alterations are significantly associated to clinicopathological features of poor prognosis, the inclusion of both p53 phenotype and TP53 mutation status into a predictive panel of tumor markers for bladder cancer is recommended.