成纤维细胞生长因子受体3及p53蛋白表达与膀胱癌预后关系的研究

目的 探讨膀胱癌组织中成纤维细胞生长因子受体3(FGFR3)、p53蛋白表达及与膀胱癌预后的关系.方法 免疫组织化学法检测108例膀胱癌组织和8例正常膀胱黏膜中FGFR3和p53的表达.膀胱癌患者中男60例,女48例.年龄29～87岁.TNM分期Ta～T164例、T2～T4 44例.病理分级G130例,G249例、G329例.结合临床资料分析其与膀胱癌分期、分级、复发的相关性.Kaplan-Meier法和Cox回归分析法进行生存分析. 结果 108例膀胱癌组织FGFR3阳性表达59例(54.6%),其中Ta～T1肿瘤阳性表达率75.0%,T2～T425.0%;G1 70.0%、G2 57.1%、G334.5%;p53阳性表达48例(44.4%),其中Ta～T1 25.0%、T2～T4 72.7%;G1 36.7%、G2 34.7%、G369.0%.8例正常膀胱黏膜组织FGFR3、p53表达均为阴性.组间差异均有统计学意义(P＜0.01).Spearman等级相关分析表明FGFR3与p53表达不相关(P＞0.05).Kaplan-Meier法结果表明FGFR3阳性表达组较阴性表达组、p53阴性表达组较阳性表达组有较长的复发间期(P＜0.05).单因素Cox回归分析显示FGFR3表达缺失和p53过度表达与肿瘤分级分期显著相关(P＜0.05).多因素Cox回归分析表明,p53表达是膀胱癌预后的独立影响因素(OR=0.59,P=0.04).结论膀胱肿瘤组织中FGFR3蛋白过度表达及p53蛋白表达缺失提示患者预后较好.     

P_(53)蛋白和增殖细胞核抗原在膀胱癌中的表达及意义

采用免疫组化法对69例膀胱移行细胞癌中P_(53)蛋白及增殖细胞核抗原(PCNA)进行检测。发现膀胱癌中P_(53)蛋白的过度表达与病理分级无关,而与临床分期及预后有关。PCNA-LI与病理分极、临床分期及预后均相关,随着肿瘤分级、分期的增高,PCNA-LI呈明显上升趋势;P_(53)蛋白过度表达或PCNA高表达组术后5年生存率明显低于P_(53)蛋白非过度表达或PCNA低表达组。结果表明:P_(53)蛋白的过度表达在膀胱癌发生、发展中起着一定作用,PCNA是判定膀胱癌恶性程度及预后的重要指标,同时发现膀胱癌中P_(53)蛋白的过度表达与PCNA-LI相关。     

膀胱癌复发与p53、p21WAF1/CIP1和细胞周期素E基因表达的相关性研究

目的：探讨膀胱癌p53、p21^WAF1/CIP1和细胞周期素E(CyclinE)基因的表达、相互间的调控及其与膀胱肿瘤复发生为的关系。方法：采用免疫组织化学链霉菌抗生物素蛋白过氧化物酶法（SP）检测64例有随访资料的膀胱癌患者p53、p21^WAF1/CIP1、CyclinE基因和Ki-67抗原表达，并用双变量相关分析、Kaplan-Meier分析及Cox regression多因素分析。结果：p53与p21WAF1/CIP1之间有明显相关（rs=-0.630，P=0.000）。p21^WAF1/CIP1与CylinE之间无明显相关（rs=-0.160，P=0.206），p53、Ki-67阳性表达患者有较高的肿瘤复发率。结论：肿瘤的临床病理特征、p53、Ki-67可作为评估膀胱肿瘤恶性程度及预后的指标。     

c-FLIP及突变p53蛋白表达与膀胱癌预后关系的研究

目的研究膀胱癌中细胞型Fas相关死亡域样白介素-1β转换酶抑制蛋白（c-FLIP）、突变p53蛋白的表达与膀胱癌预后的关系。方法采用免疫组织化学方法测定82例膀胱癌组织和10例正常膀胱黏膜中c-FLIP和突变p53蛋白的表达。膀胱癌患者中,男66例,女16例,年龄45～90岁。2002年TNM分期Ta～T129例、T2～T453例。WHO1973年病理分级G1级12例、G2级41例、G3级29例。结合临床资料分析其与膀胱癌分期、分级、复发的相关性。采用SPSS 13.0软件包分析其表达与肿瘤组织学性状的关系以及对患者预后的影响。结果82例膀胱癌组织中c-FLIP的阳性表达率为62.2%（51/82）,其中Ta～T1肿瘤阳性表达率为37.9%,T2～T4肿瘤阳性表达率为75.5%;突变p53蛋白的阳性表达率为45.1%（37/82）,其中Ta～T1肿瘤阳性表达率为24.1%,T2～T4肿瘤阳性表达率为56.6%。10例正常膀胱黏膜中c-FLIP和突变p53蛋白的表达均为阴性。c-FLIP与p53蛋白在不同的分期组间阳性表达差异均有统计学意义（P〈0.05）;生存分析发现c-FLIP与突变p53蛋白表达对生存具有明显影响（P〈0.05）。结论c-FLIP与突变p53蛋白对评价膀胱癌的侵袭性和预后都是一个重要的独立因素。膀胱肿瘤组织中的c-FLIP及突变p53蛋白表达缺失提示患者预后较好。     

膀胱癌组织微血管密度和NET-1蛋白表达及其相关性研究

目的探讨膀胱癌组织中微血管密度(MVD)和NET-1蛋白表达在膀胱癌预后判断中的意义.方法采用免疫组化SP法检测43例膀胱癌和10例正常膀胱组织中NET-1蛋白表达,以血管内皮细胞表面抗原CD105单抗标记测定MVD,分析NET-1蛋白表达和MVD与膀胱癌病理分级、TNM分期及预后的关系,采用等级相关分析膀胱癌组织MVD与NET-1蛋白表达的相关性.结果MVD与膀胱癌TNM分期及WHO病理分级相关(F1=17.01,F2=12.06,P＜0.01),MVD高表达者预后较差(P＜0.01);NET-1阳性组MVD显著高于NET-1阴性组(t=2.693,P＜0.01);相关分析NET-1蛋白表达与膀胱癌MVD呈显著正相关(r=0.331,P＜0.05).结论MVD是影响膀胱癌预后的因素之一,NET-1可能在膀胱癌组织微血管以及肿瘤形成中发挥作用.     

核转录因子 κ B、P53在膀胱癌组织中的表达及其与临床病理特征的关系

目的:探讨核转录因子κB(NF-κB)、P53蛋白在膀胱尿路上皮癌组织中的表达及其与患者临床特征及术后复发的关系。方法:选择2014年2月—2017年1月成都市郫都区人民医院确诊并手术的膀胱移行上皮癌患者48例、同期手术治疗的非膀胱癌患者16例,采用免疫组织化学SP法检测膀胱癌组织、癌旁组织及非膀胱癌患者正常尿路黏膜组织中NF-κB和P53蛋白的表达水平。探讨NF-κB和P53蛋白阳性表达与患者临床特征包括年龄、性别、病理分级、临床分期、淋巴结转移及术后复发情况的关系。结果:膀胱尿路上皮癌组织、癌旁组织和正常尿路黏膜组织中NF-κB蛋白阳性表达率分别为52.5%(30/48)、16.7%(8/48)和6.3%(1/16);P53蛋白阳性表达率分别为72.9%(35/48)、45.8%(22/48)和12.5%(2/16),癌组织>癌旁组织>正常尿路黏膜组织(P<0.05);NF-κB阳性表达与膀胱尿路上皮癌患者肿瘤病理分级存在相关性,高级别膀胱尿路上皮癌(G2/G3)组织中NF-κB阳性率显著高于低级别(G1)肿瘤组织(P<0.05);P53阳性表达与膀胱尿路上皮癌患者肿瘤分期存在相关性,T2-3期患者阳性率显著高于Tis-1期(P<0.05);NF-κB表达阳性和阴性患者的中位无疾病进展生存时间(DFS)分别为8.9个月和30.1个月,阳性组复发风险显著高于阴性组(P<0.05);P53表达阳性和阴性患者的DFS分别为9.2个月和28.6个月,阳性组复发风险显著高于阴性组(P<0.05)。结论:与正常膀胱黏膜比较,膀胱尿路上皮癌患者NF-κB、P53蛋白表达水平显著上调,并与患者肿瘤分级和分期有关,可作为膀胱尿路上皮癌术后复发预测的分子标志物。     

P53及MVD与肝细胞性肝癌肝移植术后肿瘤复发的关系

目的 探讨肝细胞性肝癌(HCC)中P53蛋白表达及肿瘤微血管密度(MVD)与HCC肝移植术后肿瘤复发的关系.方法 采用免疫组化检测HCC组织中P53蛋白表达,CD34标记癌组织血管内皮细胞,计算MVD,统计分析两者及临床病理因素与肝移植术后肿瘤复发的关系、两者与临床病理因素之间及两者相互之间的关系.结果 单因素分析表明P53蛋白表达、MVD、肿瘤TNM分期及肿瘤脉管浸润对HCC肝移植术后肿瘤复发均有影响(P<0.05),多因素分析后,仅P53和MVD为独立的影响因素;P53蛋白表达和MVD与肿瘤脉管浸润显著正相关(P<0.05);P53蛋白表达阳性的肝癌组织MVD显著高于阴性表达者(P=0.01).结论 P53蛋白表达和MVD对预测HCC肝移植术后的肿瘤复发有重要价值;P53蛋白表达阳性和高MVD者易出现肿瘤脉管浸润;P53蛋白表达与肿瘤血管生成密切相关.     

细胞周期蛋白E和p27kip1在膀胱癌中的表达及意义

目的　探讨细胞周期蛋白E(cyclinE)和p2 7kip1在膀胱移行细胞癌中的表达及临床意义。　方法　采用免疫组化SP法观察 69例膀胱癌石蜡标本中cyclinE和 p2 7kip1的表达情况 ,结合临床资料进行分析。　结果　膀胱癌组织中cyclinE和 p2 7kip1阳性表达率分别为 42 %和 51 %。cy clinE阳性表达率在复发肿瘤中及随病理分级升高而升高 (P <0 .0 5) ,但与临床分期无关 (P >0 .0 5) ;p2 7kip1阳性表达率随病理分级、临床分期升高及在复发肿瘤中下降 (P <0 .0 1 )。cyclinE与 p2 7kip1二者的阳性表达有显著相关性 (P <0 .0 1 )。　结论　cyclinE和p2 7kip1表达可能是判断膀胱癌生物学行为的重要指标     

采用基因表达数据集分析UBE2C与膀胱癌临床病理特征和预后的相关性

目的分析UBE2C基因表达与膀胱癌患者临床病理特征及预后的相关性。方法采用Oncomine数据库整合分析出肌层浸润性膀胱癌与正常膀胱组织表达差异最显著的基因作为候选目的基因,然后采用GSE13507基因表达数据集来分析该目的基因与膀胱癌临床病理特征和预后的相关性。结果 Oncomine数据库分析得到UBE2C为差异最显著的基因。GSE13507基因表达数据集分析结果显示,UBE2C基因表达水平在男性中高于女性(P=0.005),在肌层浸润性膀胱癌患者中高于非肌层浸润性膀胱癌患者(P=0.001),在T分期(P=0.001)和N分期(P=0.036)更高者高于分期更低者,在肿瘤进展患者中高于无进展患者(P=0.011);但在患者年龄(P=0.264)、远处转移(P=0.711)和肿瘤复发(P=0.481)方面无统计学差异。UBE2C基因诊断膀胱癌的曲线下面积为0.804,生存分析显示UBE2C基因高表达组的预后差于低表达组(HR=1.82,95%CI:1.13～2.94,Logrank P=0.011)。结论 UBE2C基因高表达可能与膀胱癌肌层浸润、高T分期、高N分期和不良预后相关。     

乳腺癌中c-met及p53表达与血管生成的关系

目的探讨c-met及p53表达在乳腺癌血管生成中的作用及其临床意义.方法应用SP免疫组化方法和计算机图像分析技术,对80例乳腺癌、20例乳腺纤维腺瘤的微血管计数(MVC)和c-met及p53蛋白的表达进行定量测定.结果乳腺癌组织中MVC和c-met及p53的阳性表达与乳腺癌的组织学分级、腋窝淋巴结转移及肿瘤分期有关 (P＜0.01).MVC在c-met及p53表达阳性者明显高于c-met及p53表达阴性者,两者间差异有显著性意义 (P＜0.01).结论 c-met及p53共同参与调控乳腺癌的肿瘤血管生成.     

Evaluation of p53 nuclear accumulation in low- and high-grade (WHO/ISUP classification) transitional papillary carcinomas of the bladder for tumor recurrence and progression

OBJECTIVES: To evaluate the association of p53 nuclear accumulation with recurrence and progression in transitional cell carcinomas of the bladder and to examine the distribution of p53 in low-grade and high-grade transitional cell carcinomas according to the World Health Organization/International Society of Urological Pathology classification. PATIENTS AND METHODS: Nuclear accumulations of p53 were examined in a total of 99 patients with transitional cell carcinoma between May 1995 and October 1999. The mean age was 64 years. There were 94 (95%) men and 5 (5%) women. Following resection, surgical specimens were examined, and p53 accumulation with a 20% cutoff value was accepted as positive staining. Of the 99 patients, 52 (53%) had histologically superficial bladder tumors, and 47 (47%) had invasive tumors. Data concerning grade, stage, number of recurrences, and disease progression were available for each patient. RESULTS: The median follow-up period was 55 months. 60 of the 99 patients (61%) had p53 overexpression. The difference for p53 overexpression between low-grade and high-grade tumors was significant (p < 0.05). In low- and high-grade tumors, there was no significant relationship for recurrence between p53-positive and p53-negative groups. But there was a statistically significant relationship between progression and histological grade of the tumors. p53 had no significant relationship with tumor recurrences (p > 0.05), but its relationship with progression was statistically significant (p < 0.05). CONCLUSIONS: We did not find a correlation between tumor recurrence and p53 overexpression, but p53 overexpression has a predictive value in determining tumor progression. High-grade tumors had higher p53-positive values than low-grade tumors. This group of patients should be considered for radical therapies on the basis of other prognostic parameters.     

P21WA F_1/CIP_1和P53基因表达与膀胱癌生物学行为的关系

目的 :探讨膀胱癌 P2 1WAF1 / CIP1 、P5 3基因的表达、相互间的调控及其与生物学行为的关系。方法 :采用免疫组织化学 ABC方法检测 12 2例有随访结果的膀胱癌患者的 P2 1WAF1 / CIP1 、P5 3基因表达 ,并采用双变量相关分析、L ogistic回归分析和 Kaplan- Meier法分析。结果 :P5 3野生型肿瘤中 P2 1WA F1 / CIP1 阳性表达率明显高于 P5 3突变型肿瘤 ;P5 3突变型肿瘤中保持 P2 1WAF1 / CIP1 阳性表达者具有与 P5 3野生型肿瘤同样低的复发率和较长的生存期。结论 :维持 P2 1WAF1 / CIP1 的表达可清除 P5 3突变蛋白的有害作用 ;根据 P2 1WAF1 /CIP1 表达状况 ,结合临床分期可对膀胱癌的恶性程度及预后作出更准确的评估 ,对拟定治疗方案有重要的指导意义     

Prognostic Significance of p53 Protein Accumulation in Stage pT1 Transitional Cell Carcinoma of the Bladder

Objective: Mutations in the tumour suppressor gene p53 results in the production of a mutant type, dysfunctional p53 protein which can readily be detected in the cell nucleus by immunohistochemical staining. This study aims to investigate the association of nuclear p53 protein accumulation with the clinical outcome of stage pT1 transitional cell carcinoma of the bladder which is renowned for high rates of recurrence and progression. Methods: TUR samples of the tumours from fifty-two patients with primary stage T1 bladder cancer were analyzed immunohistochemically using the standard avidin-biotin peroxidase method for nuclear p53 accumulation. Status of p53 immunostaining was correlated with tumour recurrence, disease progression and three-year survival of each patient. Results: The rate of tumour recurrence in pT1 bladder cancer was 36% in patients with tumours stained negatively for p53 protein and 78% in patients with tumours stained positively for p53 protein. Disease progression was seen in 15% of p53 (-) patients and in 56% of p53 (+) patients. Conclusions: In stage pT1 bladder tumours p53 nuclear accumulation indicates higher rates of tumour recurrence and disease progression. Accordingly, in patients who have pT1 bladder tumours with nuclear p53 accumulation, institution of more aggressive therapy should be considered and early radical therapeutic modalities should be offered to these patients.     

The predictive value of muscularis mucosae invasion and p53 over expression on progression of stage T1 bladder carcinoma

PURPOSE: We determine the significance of muscularis mucosae invasion and nuclear p53 over expression on the progression of stage T1 transitional cell bladder cancer. MATERIALS AND METHODS: The pathological findings in 149 cases of T1 tumors diagnosed between 1973 and 1996 were reviewed. Diagnosis was stage T1 in 94 tumors in which the muscular layer was clearly identifiable and disease-free. Mean followup was 64.9 months (range 5 to 288). T1 bladder cancers were subclassified into 2 groups, with (T1b) or without (T1a) muscularis mucosae invasion. The p53 nuclear antibody immunoreactivity was determined with antibody D07 and a cutoff point at 15%. RESULTS: T1 subclassification was possible in all 94 patients. Of all tumors 37.2% expressed p53 nuclear over expression. Univariate statistical analysis showed that p53 expression (p <0.05) and tumor invasion depth (p <0.001) significantly correlated with progression. However, on multivariate analysis only invasion depth (p <0.0001) and associated carcinoma in situ (p <0.03) remained independently significant as predictors of progression. CONCLUSIONS: In our study the depth of tumor invasion was a significant independent predictor of progression in patients with T1 bladder cancer. This result suggests that the depth of invasion in stage T1 should be included in the histopathological report.     

Overexpression of p27kip1 in urinary bladder urothelial carcinoma

OBJECTIVES: Cyclins and cyclin-dependent kinase (CDK) complexes have important regulatory roles during cell cycle progression and can be used as prognostic markers in various kinds of malignant tumors. This study investigated the expression of proliferative cell nuclear antigen (PCNA), p53, Rb, p27(kip1), and cyclin D1 by immunostains in bladder tumors, especially urothelial papilloma, papillary urothelial neoplasm of low malignant potential, and low and high grade urothelial carcinoma, to see if their expression is associated with classification or grading of the urinary bladder urothelial carcinoma. METHOD: Nuclear expression of PCNA, p53, Rb, p27(kip1), and cyclin D1 was determined immunohistochemically in a series of 89 urinary bladder tumor specimens, including 13 papilloma, 15 urothelial neoplasm of low malignant potential, 17 low grade urothelial carcinoma, and 44 high grade urothelial carcinoma. The results of immunoreactivity were analyzed with respect to the associations with tumor grade. RESULTS: Eighty-two percent (38/45) of the p27(kip1) positive tumors were urothelial carcinoma, and the percentage of the p27(kip1) positivity was higher with increasing grade of the urothelial carcinoma (P = 0.011). A tendency of higher percentage of positive p53 immunoreactivity was noted in the urothelial carcinoma (P = 0.053). There was no significant difference in cyclinD1, Rb and PCNA expression between benign, low malignant potential and urothelial carcinoma. CONCLUSION: We first noted an overexpression of p27(kip1) in urinary bladder urothelial carcinoma. The result indicates that some urothelial carcinomas may tolerate this inhibitor of cell cycle progression.     

Association of cyclin D1 and E1 expression with disease progression and biomarkers in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder

PURPOSE: To determine the association of cyclin D1 and E1 expression with bladder cancer presence, clinical and molecular characteristics, and disease progression in patients with nonmuscle-invasive urothelial cell carcinoma of the bladder. METHODS: Immunohistochemical staining for cyclin D1, cyclin E1, p53, p21, p27, pRB, KI-67, and survivin was performed on a tissue microarray containing specimens from 9 normal controls and 74 patients with Ta, Tis, and/or T1 urothelial cell carcinoma of the bladder. Cyclin D1 and E1 immunoreactivity were considered low when samples showed less than 10% and 30% nuclear reactivity, respectively. RESULTS: Normal bladder urothelium from all 9 control patients showed uniformly intense expression of cyclin D1 and cyclin E1. Cyclin D1 and E1 expression were low in 23 of 74 (31.1%) and 27 of 74 (36.5%) specimens. Kaplan-Meier analyses showed that low expression of cyclin E1 was significantly associated with an increased probability of tumor recurrence and progression in univariate, but not multivariate analysis. Cyclin D1 immunoreactivity was not associated with any pathologic characteristics or clinical outcomes. Low cyclin E1 expression was significantly associated with altered expression of p53, pRB, KI-67, and survivin. CONCLUSIONS: Tissue expression of cyclin D1 or E1 seems not to add independent prognostic value to standard features in patients with nonmuscle -invasive urothelial cell carcinoma of the bladder.     

Detection of p53 tumor-suppressor-gene protein in bladder tumors and prostate cancer: possible clinical implications

Summary For a variety of human malignancies such as breast cancer and cancer of the prostate, p53 oncoprotein overexpression indicating an alteration of the p53 tumorsuppressor gene has been described as a prognostic factor for a poor clinical outcome. To investigate the overexpression of p53 oncoprotein in transitional-cell carcinoma of the bladder, 58 bladder cancer specimens of different clinical stages and histological grades were investigated using an immunohistochemical approach. A correlation between p53 positivity and tumor stage was observed, with an increase from 38.5% of superficial (T_a) tumors to 83.3% of muscle-invasive (T₃/T₄) tumors staining positively for p53 oncoprotein. Furthermore, an increase from 46.7% of G₁ tumors to 75% of G₃ tumors was observed. In 22 of 25 (87%) informative patients the results of the immunohistochemical staining could be verified by the determination of p53 mutations as detected by polymerase chain reaction (PCR)-directed analysis of restriction-fragment-length polymorphisms (RFLP). To determine the prognostic value of p53 immunohistochemistry for the clinical course of superficial bladder cancer, the overexpression of p53 oncoprotein was investigated in 41 patients with superficial bladder tumors (T₁) undergoing complete transurethral tumor resection. The detection of p53 protein was correlated with further clinically important variables such as sex, age, histological grading, former instillation therapy, and immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating-cell nuclear antigen; monoclonal antibody PC10). After a median follow-up period of 54 months, 7 of 8 patients for whom more than 20% of cells stained positively for p53 had disease progression as compared with only 1 of 33 patients who were negative for p53 detection (P<0.01; chi-square test). For other urological tumors such as prostate cancer, the results of immunohistochemistry are more difficult to interpret and require definite confirmation on the DNA level.     

p53与端粒酶逆转录酶在膀胱移行上皮癌的表达和作用

目的探讨p53和端粒酶逆转录酶（hTERT）在膀胱移行上皮癌的表达和作用。方法应用免疫组织化学方法和原位分子杂交检测膀胱移行上皮癌的组织学标本的p53蛋白和hTERT mRNA表达，结合病理学和临床资料进行相关分析。结果62例标本中p53阳性表达21例（33．87％），hTERT阳性表达48例（77．42％）。p53的表达与肿瘤的病理学分级显著相关（P〈0．01），与肿瘤的复发显著相关（P〈0．01）。hTERT的表达与肿瘤的分级、分期及复发无相关性。结论p53基因和端粒酶参与了膀胱移行上皮癌的发生和进展。p53蛋白阳性表达有较高的肿瘤分级，并且更可能复发。hTERT可作为临床膀胱移行上皮癌的诊断指标之一。     

p53 nuclear accumulation is not associated with decreased disease-free survival in patients with node positive transitional cell carcinoma of the bladder

PURPOSE: Although the majority of patients with node positive transitional cell carcinoma of the bladder have disease progression, a definitive subset is cured by surgery only. Nuclear accumulation of p53 has been associated with disease progression in patients with superficial transitional cell carcinoma and decreased survival in those with muscle invasive disease. We determined whether p53 status would predict survival in a cohort with nodal metastasis. MATERIALS AND METHODS: We explored the comprehensive database of all 199 radical cystectomies performed at our institution between July 1988 and September 1999. The 59 patients in this database with node positive pathology comprise our study. We performed immunohistochemical analysis of specimens using the MAB1801 antibody with greater than 20% lymph node and primary tumor nucleus staining deemed positive. Additional covariates measured included patient age, sex, pathological disease stage, adjuvant chemotherapy and nodal stage. Disease-free survival curves were generated for the various covariates and compared using the log rank test. The Cox proportional hazards technique was used to determine covariate adjusted p53 survival. RESULTS: In the cohort overall median disease-free survival was only 21 months, although 18% of patients were disease-free at 5 years. There was evidence of p53 nuclear accumulation in 54% of cases and complete agreement of nodal with bladder p53 nuclear accumulation. No significant baseline differences were noted in the covariates with respect to p53 nuclear accumulation. For stratum specific disease-free survival univariate and multivariate analyses revealed that only pathological stages p0-p2b versus p3-p4 (hazards ratio 2.86, p = 0.03), and nodal stages N2 versus N1 and N3 versus N1 (hazards ratio 3.84, p = 0.01 and hazards ratio 13.3, p = 0.0002, respectively) were significantly associated with prolonged disease-free survival, while p53 nuclear accumulation was not. CONCLUSIONS: Despite credible evidence for p53 nuclear accumulation prognostication in patients with in situ and invasive transitional cell carcinoma, this marker is not predictive of disease-free survival in node positive disease.