Gao J P, Uchida T, Wang C, Jiang S X, Matsumoto K, Satoh T, Minei S, Soh S, Kameya T, Baba S
Department of Urology, Kitasato University School of Medicine, Sagamihara, Kanagawa 228-8555, Japan.
Int J Oncol. 2000 Mar;16(3):469-75. doi: 10.3892/ijo.16.3.469.
Although the mutated p53 gene has been postulated to induce immunohistochemically-detectable p53 protein, reports regarding the relationship between p53 mutation and p53 protein expression have been contradictory. This study investigated the relationship between p53 mutations and p53 expression and their clinical significance for patients with transitional cell carcinoma of the bladder. Eighty-seven transitional cell carcinoma of the bladder were analyzed by immunohistochemistry (IHC) for p53 nuclear accumulation, and the results compared to mutations detected in the p53 gene evaluated by polymerase chain reaction single-strand conformation polymorphism (SSCP) and DNA sequence analysis. By p53 IHC analysis, positive p53 staining was observed in 50 (57.5%) of the 87 tumors. The specificity of IHC, defined as a percentage of IHC negative (<20%) tumors among tumors without mutation, was 94.6%. Despite the good concordance between p53 mutation and p53 protein expression (p<0.0001), 48.0% (24/50) of the tumors showed p53 overexpression without mutation, and 2 (5.4%) tumors with mutation showed no p53 immunoreactivity. Patients with higher grade (grade 3), stage (stages pT2-4), and p53 mutations had a poorer prognosis by Kaplan-Meier survival analysis. A Cox univariate analysis found that grading (hazard ratio 3.139; p=0.002), staging (hazard ratio 3.832; p=0.0005) and p53 mutation (hazard ratio 2.498; p=0.013) were significant variables in these patients, but no variable was independently associated with an increased survival of bladder carcinoma by multivariate analysis. We found that a 20% cut-off level of p53 overexpression showed the highest correlation with prognosis and p53 mutation, however, p53 overexpression and mutation were not superior to staging as prognostic markers. These data suggest that careful assessment of the TNM staging system remains the most reliable predictive indicator of survival for patients with transitional cell carcinoma of the bladder.
尽管已推测突变的p53基因可诱导免疫组化可检测到的p53蛋白，但关于p53突变与p53蛋白表达之间关系的报道一直相互矛盾。本研究调查了p53突变与p53表达之间的关系及其对膀胱移行细胞癌患者的临床意义。采用免疫组化（IHC）分析87例膀胱移行细胞癌的p53核聚集情况，并将结果与通过聚合酶链反应单链构象多态性（SSCP）和DNA序列分析评估的p53基因中检测到的突变进行比较。通过p53 IHC分析，在87例肿瘤中有50例（57.5%）观察到p53阳性染色。IHC的特异性定义为无突变肿瘤中IHC阴性（<20%）肿瘤的百分比，为94.6%。尽管p53突变与p53蛋白表达之间具有良好的一致性（p<0.0001），但48.0%（24/50）的肿瘤显示p53过表达但无突变，2例（5.4%）有突变的肿瘤未显示p53免疫反应性。通过Kaplan-Meier生存分析，高级别（3级）、高分期（pT2-4期）和p53突变的患者预后较差。Cox单因素分析发现分级（风险比3.139；p=0.002）、分期（风险比3.832；p=0.0005）和p53突变（风险比2.498；p=0.013）是这些患者的显著变量，但多因素分析中没有变量与膀胱癌生存率增加独立相关。我们发现p53过表达的20%截断水平与预后和p53突变的相关性最高，然而，p53过表达和突变作为预后标志物并不优于分期。这些数据表明，仔细评估TNM分期系统仍然是膀胱移行细胞癌患者生存最可靠的预测指标。
