Expression of pS2 protein and its relation with the Ki-67 proliferative indices and tumor recurrence in superficial bladder carcinomas

OBJECTIVE: To investigate the expression and possible role of pS2 protein as a predictor of tumor recurrence in superficial transitional cell carcinoma of the bladder and to determine its relation with tumor stage, grade, size, number, recurrence and proliferative activity. METHODS: Paraffin sections of transurethral resection material from 80 patients with superficial transitional cell bladder carcinoma were stained with pS2 and Ki-67 antibodies using the standard streptavidin biotin immunoperoxidase method. Cytoplasmic pS2 staining was scored on a scale of 1-3 and the Ki-67-labelling index was determined as a percentage of positively staining tumor cells. RESULTS: An inverse relationship was found between pS2 expression and Ki-67 index (p<0.001). pS2 expression showed no relation with any clinicopathological prognostic parameters as well as the recurrence rate. The recurrence rate was only associated with increased tumor number (p = 0.05), while the time to first recurrence was significantly related to tumor size, proliferative activity and tumor grade (p = 0.04, p<0.001, and p = 0.03, respectively). On the other hand, higher tumor grade was correlated with increased tumor number, Ki-67 index and tumor stage (p = 0.016, p = 0.006, and p<0.001, respectively). CONCLUSION: pS2 expression is associated with a low proliferative potential of superficial transitional cell carcinoma of the bladder, while it does not seem to be related to the recurrence rate of the tumor and other prognostic factors. Tumor size and proliferative activity may aid in the estimation of the time to the first recurrence.     

Evaluation of P53 protein overexpression, Ki67 proliferative activity and mitotic index as markers of tumour recurrence in superficial transitional cell carcinoma of the bladder

OBJECTIVES: To confirm the interrelationship between p53, ki67, mitotic index with others known prognostic factors such us stage, grade, multifocality, tumour size, history of recurrence in transitional cell carcinoma (TCC) of the bladder and to determine the prognostic impact of p53, Ki67 and mitotic index in predicting recurrence in superficial bladder cancer. METHODS: Two hundred and fourteen patients with apparently superficial TCC of the bladder underwent TURBT and the 192 histologically Ta-T1 were divided into 104 primary lesions (group 1, mean follow-up 26 months) and 88 recurrent tumours (group 2, mean follow-up 28 months). Data concerning focality, tumour size, number of recurrences and recurrence-free survival were considered in each patients. All samples were immunohistochemically stained with p53 and Ki67 monoclonal antibodies. Mitotic index (MI) was calculated on haematoxylin and eosin stained sections. RESULTS: Recurrence-free survival was significantly lower in superficial recurrent tumours (group 2) compared with primary tumours (group 1). P53 staining was correlated with grade and stage for both 5 and 20% positivity thresholds. Ki67 and MI were significantly different over strata defined by stage, grade and focality in both patients groups but only Ki67 showed a correlation with p53 status. Recurrence-free survival could not be predicted either by p53 status or MI. A 20% cut-off level of Ki67 staining resulted a good predictor of recurrence in group 1 Ta-T1/G1-G2 tumours (p = 0.03). Only Ki67 and multifocality were found to be independent prognostic factors of recurrence in multivariate analysis. Stratifying Ta-T1/G1-G2 patients according to these variables, Ki67 provided a useful tool to predict early recurrence in monofocal lesions from both groups. CONCLUSIONS: P53 and MI despite a fairly good correlation with traditional prognostic factors in bladder TCC seem to play no role in the prediction of tumoural recurrence. A Ki67 index over 20% predicts those single well-differentiated (Ta-T1/G1-G2) tumours which are likely to recur within one year of treatment.     

Immunohistochemical study of p53 and Ki-67 overexpression in grade 3 superficial bladder tumor in relationship to tumor recurrence and prognosis]

PURPOSE: The major drawback of the current treatment for superficial bladder tumor is the high rate of recurrence. Especially, the tumor with grade 3 component has a tendency to recur and progress in stage. However, we have difficulty in predicting tumor recurrence and stage progression accurately by conventional clinicopathological factors. We evaluated the efficacy of p53 and Ki-67 overexpression as a predictor of recurrence or prognosis in patients with superficial bladder tumor of grade 3. MATERIALS AND METHODS: Samples were obtained from 41 patients with superficial transitional cell carcinoma of the bladder of grade 3 who were treated by transurethral resection (TUR). The immunohistochemical study was performed using the antibodies against the p53 protein and Ki-67 antigen on formalin-fixed, paraffinembedded tissue specimens from initial tumors. We evaluated the correlation between these results and several clinicopathological factors. RESULTS: The p53 index and the Ki-67 index in pTa, pT1a and pT1b tumors were 26.4 +/- 30.1%, 28.6 +/- 30.0%, and 34.6 +/- 32.6% (p53) and 20.5 +/- 22.5%, 20.0 +/- 29.3%, and 29.2 +/- 28.4% (Ki-67). There was no significant difference between the each index and tumor stage. Eighteen cases (43.9%) had intravesical recurrence. The p53 index of the initial tumor from the tumor free cases (n = 23), recurrent cases without stage progression (n = 12), and stage progression cases (n = 6) were 19.7 +/- 28.2%, 42.0 +/- 28.7%, and 42.5 +/- 32.0%. Between the recurrence-free cases and the recurrent cases without progression, the p53 index of the initial tumor had statistical significance (p < 0.05). The Ki-67 index was shown to be the same pattern as the p53 index, but there was not statistical significance. Four of patients with stage progression had tumor progression within six months. Three of the patients with tumors with stage progression died of the cancer. In multivariate analysis, tumor multiplicity (p = 0.01), BCG intravesical instillation (p = 0.04), p53 index (p = 0.01) and Ki-67 index (p = 0.02) were the positive risk factors for tumor recurrence, but only the p53 index was the positive risk factor for prognosis fo the patients (p = 0.03). CONCLUSION: These results suggest that the immunohistochemical study of p53 overexpression is a useful predictor for tumor recurrence and prognosis in patients with superficial bladder tumor with grade 3.     

Tissue microarray analysis of the prognostic value of E-cadherin, Ki67, p53, p27, survivin and MSH2 expression in upper urinary tract transitional cell carcinoma

OBJECTIVES: Invasive upper urinary tract transitional cell carcinoma (UUT-TCC) has a poor prognosis (survival <50% at 5 years), and tumor stage and grade often fail to predict outcome. Our purpose was to establish whether the expression of Ki67, p53, p27, E-cadherin, survivin or MSH2 can provide prognostic information in UUT-TCC. METHODS: The following data from the files of 62 patients treated for UUT-TCC over 12 years were collated: age at diagnosis, prior history of cancer, tobacco consumption, tumor stage (including surgical margins) and grade, and disease progression. Immunohistochemistry (IHC) for Ki67, p53, p27, E-cadherin, survivin and MSH2 was performed on tissue microarray sections from tumor tissue. RESULTS: Overall, 31 patients died with metastasis from UUT-TCC. Mean survival was 20+/-16 months (range 2-83). In a univariate analysis, advanced age (>68 years), high stage, and loss of E-cadherin and high Ki67 expression were associated with a poor prognosis and disease recurrence. In a multivariate analysis, the independent factors of prognosis and recurrence were E-cadherin (p=0.001; p=0.004), age (p=0.022; p=0.008), and high stage (p=0.023; p=0.008). CONCLUSIONS: E-cadherin is a useful independent prognostic factor in UUT-TCC, for use in addition to age and tumor stage. It is of particular interest to predict recurrence in patients with low grade non-invasive tumors. Ki67 expression is informative but less significant. Survivin, p53, p27 and MSH2 have no prognostic value.     

乳腺癌p53，ki-67和bcl-2的表达与新辅助化疗的关系

目的 研究乳腺癌p53,ki-67和bcl-2基因蛋白表达与新辅助化疗临床效果的关系,以寻找指导治疗、判断预后的生物学指标.方法 采用免疫组化SABC法测定118例可手术的乳腺癌标本的p53,ki-67和bcl-2的蛋白表达,并分析其与新辅助化疗疗效的关系.结果 术前辅助化疗有效率为68.6%.p5 3表达阳性,化疗效果差（P＜0.05）;而ki-67阳性表达者有效率明显高于ki-67不表达者（P＜0.05）;bcl-2表达与疗效无明显关系.p53蛋白阳性表达者bcl-2表达下降.p53与ki-67蛋白表达有明显关系.结论 p53和ki-67蛋白表达可作为指导新辅助化疗及预后判断的分子生物学指标.     

P16 immunoreactivity is an independent predictor of tumor progression in minimally invasive urothelial bladder carcinoma

OBJECTIVE: To evaluate the prognostic impact of p16 immunoreactivity in minimally invasive transitional cell bladder carcinomas (stage T1). METHODS: Multi-tissue-arrays containing 73 samples of T1 bladder carcinomas were stained immunohistochemically for p16. Additionally, p53 and Ki-67 antigen expression were examined. A multivariate analysis including other prognostically relevant factors like tumor grade and sub-stage was performed. RESULTS: Loss of p16 expression occurred in 54% of cases and was significantly associated with reduced progression-free (p=0.018 by univariate analysis), but not with recurrence-free survival (p=0.341). Median Ki-67 antigen and p53 index were 51% (range, 1-93%) and 10% (range, 0-100%), respectively. Both indices correlated significantly (p=0.041 and p=0.024, respectively) with recurrence-free, but not with progression-free survival. Also tumor grade was significantly associated with tumor recurrence (p=0.006). By multivariate analysis, tumor grade (p=0.008) was identified as an independent predictor of tumor recurrence, whereas p16 expression (p=0.009) was identified as an independent predictor of tumor progression. CONCLUSION: According to our data, there is a significant correlation between loss of p16 expression and tumor progression in patients with minimally-invasive bladder cancer. Immunohistochemical p16 staining may therefore represent a useful tool of providing additional information on the clinical outcome of these patients.     

Livin在膀胱移行细胞癌中的表达及其与ki-67的关系

目的研究凋亡抑制蛋白家族（IAP家族）新的凋亡抑制因子livin在膀胱移行细胞癌（BTCC）中的表达及其与肿瘤分级、分期的关系及livin和ki-67在BTCC中表达的关系。方法采用免疫组化SP法对36例BTCC和8例正常膀胱黏膜livin和ki-67的表达进行检测,分析两者在膀胱癌组织和非膀胱癌组织中的表达,livin的表达与BTCC病理学分级、临床分期及与ki-67表达的关系。结果Livin在8例正常膀胱组织中均不表达,而在36例BTCC组织中的阳性表达率为86．1％（P〈0．01）。livin的表达和BTCC的病理分级,临床分期、k-67的表达无明显相关（P〉0．05）。结论细胞凋亡抑制因子livin在BTCC组织中表达上调,提示livin可能通过抑制细胞凋亡,对BTCC的发生发展起重要作用;但是我们的实验表明livin与调控细胞周期,促进细胞增殖无明显相关。Livin在膀胱癌中的高表达,有望成为一种有效、敏感的瘤标,并为BTCC的基因治疗提供新靶点。     

Relevance of p53 gene alterations for tumor recurrence in patients with superficial transitional cell carcinoma of the bladder

PURPOSE: The prognostic relevance of p53 protein accumulation in muscle-invasive bladder carcinoma is well documented, but the prognostic relevance of p53 alterations in superficial bladder tumors remains uncertain. Immunohistochemical data are divergent, possibly because of the use of nonstandardized techniques. We therefore investigated the relevance of p53 gene point mutations and loss of heterozygosity (LOH) for tumor recurrence. The results of this molecular analysis were compared with accumulation of the p53 protein as shown by immunohistochemistry. MATERIAL AND METHODS: Representative tumor tissue was selected and microdissected from 40 patients (pTa, 18 patients; pT1, 22 patients; grade I, 7 patients; grade II, 28 patients; grade III, 5 patients). Polymerase chain reaction (PCR) was carried out with exons 5-8. All PCR products were screened for p53 mutations with temperature-gradient gel electrophoresis (TGGE). When mobility shift was observed, direct nucleotide sequencing was performed. Detection of LOH was performed with nonradioactive microsatellite analysis using three markers (TP 53, D17S513 and D17S786) on chromosome 17p. Immunohistochemistry was performed with the DO 7 antibody. Tumor samples with p53 accumulation of 5% or more positive nuclei were classified as positive. Univariate analysis for disease-free survival was performed using Kaplan-Meier analysis and the log-rank test. RESULTS: TGGE and direct sequencing detected mutations in 10 of 40 patients (2 of 18 pTa and 8 of 22 pT1 patients). LOH was detected in 11 patients. Both a mutation and LOH were detected in 3 patients. p53 immunohistochemistry detected at least 5% positive nuclei in 28 of 40 patients (70%). After a median follow-up of 26 months 14 patients suffered disease recurrence. Whereas disease-free survival did not correlate with a mutation (p = 0.77, log-rank test), LOH (p = 0.2) or a mutation in combination with LOH (p = 0.23), a positive p 53 immunoreaction was significantly associated with short disease-free survival (p = 0.009). CONCLUSION: Despite the relatively high percentage of patients with p53 gene alteration in this population no significant correlation between the detection of molecular alteration and disease recurrence could be found. We conclude that, in contrast to immunohistochemical accumulation, gene alterations play only a minor role in tumor recurrence of p53 in patients with superficial transitional cell carcinoma of the bladder, and that immunohistochemical accumulation of the p53 protein has to be explained by mechanisms other than gene mutations.     

Pretreatment p53 nuclear overexpression as a prognostic marker in superficial bladder cancer treated with Bacillus Calmette-Guérin (BCG)

INTRODUCTION: Altered p53 gene product correlates with the stage and grade of bladder tumor, but its value as a predictor of BCG response has been disappointing. In order to revisit the prognostic value of pretreatment p53 nuclear overexpression for the BCG response, we studied a large cohort of consecutive patients with superficial bladder cancer treated with BCG. METHODS: From 1988 to 2001, 102 patients with a history of multifocal, recurrent, and/or high-risk papillary transitional cell carcinoma or carcinoma in situ, were treated for the first time with BCG. p53 immunostaining was performed on paraffin-embedded tissues using monoclonal antibody DO7 and an automated immunostainer. Special attention was paid to the conditions of tumor fixation. p53 overexpression was defined as more than 20% tumor cells with p53-stained nuclei. RESULTS: Immunostaining was significantly higher for Ta/T1 G3 +/- Cis (p < 0.001), tumoral substage T1b (p = 0.001), grade 3 (p = 0.0001), and Cis (p = 0.002). Times to recurrence, progression and cancer death were shorter among patients with p53 overexpression (p = 0.03; p < 0.0001; p = 0.0003). In multivariate analysis, p53 overexpression was an independent predictor of recurrence (p = 0.0003) [RR = 0.15; 95%CI, 0.06 to 0.42]. CONCLUSION: Pretreatment p53 nuclear overexpression in superficial bladder tumors is associated with a high risk of disease recurrence, progression and cancer death after BCG therapy. Applying antibody DO7 with an automated immunostainer and stringent fixative conditions, p53 nuclear immunostaining yields clinically relevant information and may be a useful tool for selecting patients with superficial bladder cancer who might be resistant to BCG.     

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.     

p53 Gene mutations in superficial bladder cancer

OBJECTIVES: To assess the presence of p53 gene mutations in superficial tumors of the urinary bladder (transitional cell carcinoma) and their relationship to classic prognostic factors for cancer recurrence and progression. To analyze the implication of these mutations on the P53 protein structure. MATERIALS AND METHODS: Observational, cross-sectional study of 90 consecutive patients, 60 with superficial transitional cell carcinoma (pTa and pT1) and 30 without neoplastic disease (control group). Samples of bladder tumor and control normal mucosa were analyzed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) to detect p53 mutations in exons 5-9. Automatic sequencing was used to characterize the mutations and their effect on the P53 protein was analyzed. Bivariate analysis was used to assess the association with other prognostic factors. RESULTS: PCR-SSCP found no mutations in any control group patient, whereas 38.3% of patients with superficial transitional cell carcinoma had one or more mutations in the exons analyzed. Thirty mutations were sequenced; all were point mutations and 86.67% were considered relevant for the P53 structure. A total of 93.3% of the mutations were located in highly conserved regions and 73.3% in mutational hot spots. The highest cell differentiation grades and pT1 stage were associated with a higher incidence of p53 gene mutations. Previous recurrences and other tumor-related histological variables were not associated with a higher percentage of mutations. CONCLUSION: Mutations at p53 did not appear in healthy bladder mucosa and were significantly more frequent in pT1 and high-grade (G-II and G-III) tumors. All mutations detected were point mutations and most caused considerable P53 structural abnormalities, implying major repercussions on P53 function. These data suggest that certain p53 mutations may have prognostic value, even though they were not associated with other classic recurrence and tumor progression parameters. Future analyses of the progress of patients with superficial bladder transitional cell carcinoma and mutated p53 will help clarify this aspect.     

Prognostic implications of p53 gene mutations in bladder tumors

PURPOSE: Alterations in the p53 gene related to neoplastic progression were studied in tumor tissue samples from patients with transitional cell carcinoma and correlated with classic staging parameters. On this basis, biological characterization of the tumor was performed to establish subgroups of patients at high risk and those with a more favorable prognosis. MATERIALS AND METHODS: This observational, analytical and cross-sectional study included 115 patients divided into 4 homogeneous groups of 1-control, 2-primary superficial transitional cell carcinoma, 3-recurrent superficial transitional cell carcinoma, and 4-infiltrative transitional cell carcinoma. DNA was obtained from tumor tissue samples and polymerase chain reaction-single strand conformational polymorphism analysis was performed on exons 5 to 9 of the p53 gene. Samples showing mutations were submitted to automatic sequencing. Statistics included bivariate analysis and logistic regression. RESULTS: Of the tumors the 63.8% were superficial and 37.2% were infiltrative transitional cell carcinoma. Of the infiltrative tumors 23.5% (8 of 34) resulted from recurrent transitional cell carcinoma. Mutations were found in samples from 46.8% of patients, all with bladder tumors. There was a trend toward increasing appearance of mutations as the size of the tumor, number of tumor implants, degree of dedifferentiation and stage of local infiltration increased. The presence of mutations in p53 was 2.5 times greater in infiltrative tumors than in low stage and 4.3 times greater in moderate to high grade than in low grade tumors. All mutations found were point mutations and 79.25% provoked severe alterations in protein structure. CONCLUSIONS: Mutations in the p53 gene are mainly point mutations that aggregate in hot spots, and provoke genetic instability and substantial changes that alter p53 function, implying a trend to tumor progression and dissemination (with a greater proportion of mutations in high stage high grade tumors). Since a large percentage of bladder tumors are under staged, analysis of p53 gene mutations could be useful as a factor for prognosis and therapeutic decisions.     

p53、p21、Ki-67和VEGF与膀胱癌分级、分期以及预后的关系

目的：探讨p53、p21、Ki-67和VEGF的表达与膀胱癌的病理分级、分期以及预后足否相关。方法：应用免疫组织化学染色的方法,对40例手术证实的膀胱移行细胞癌患者的病理切片进行p53、p2l、Ki-67和VEGF的化学染色。将免疫组化结果与病理分级、分期以及预后情况进行分析。结果：在40个肿榴标本中．p53、p21、Ki-67和VEGF的表达有改变的分别有31个（77.5％）．22个（55.0％）．16个（40.0％）．17个（42.5％）：其中至少1个标记物表达异常35例（87.5％）．而4个标记物均表达异常者有7例（17.5％）。患者平均随访51个月。除了Ki-67、VEGF与病理分级以及Ki-67与分期之间无统计学意义外．4个标记物多少都与膀胱癌的病理分级、分期相关。p53（＋）／p21（-）以及4个标记物同时异常是与疾病相关死亡率有关的独立因素（P＜0.05,P＜0.01）。而Ki-67、VEGF均不是膀胱癌相关死亡率的独立因素（P〉0．05）。越多标记物表达异常,则膀胱癌的死亡率增加。结论：p53、p21、Ki-67和VEGF多少都与膀胱癌的病理分级、分期相关。联合检测p53、p21、Ki-67和VEGF可以更加准确地预测膀胱癌的预后。     

Correlation and prognostic significance of p53, p21WAF1/CIP1 and Ki-67 expression in patients with superficial bladder tumors treated with bacillus Calmette-Guerin intravesical therapy

PURPOSE: We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors. MATERIALS AND METHODS: The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method. RESULTS: During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage. CONCLUSIONS: Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.     

The relation of mutant p53 accumulation in transitional cell carcinoma of bladder with pathological stage,grade, recurrence and survival

In this study prognostic significance and clinical value of mutant p53 gene in bladder transitional cell tumors is investigated.In our clinic, between 1997–2000, transurethral resection was performed in 48 cases, 3 females (6%) and 45 males (94%) with the diagnosis of primary bladder tumor, age ranges between 30–81 years old (average 58.9 ± 9.9).The patients whose pathology results were transitional cell carcinoma weregathered into two groups as p53 positive and p53 negative byimmunuhistochemical study. These cases who were followed 1–36 monthswere compared to each other for pathologic state, tumor grade, recurrenceand survival.It's found out that mutant p53 accumulation is related to high grade andpathologic stage tumors. But it's concluded that p53 positivity doesn'teffect recurrence and survival rates.     

Expression of p53 product in Chinese human bladder carcinoma

Summary Expression of p53 protein was examined in 67 cases of primary transitional cell carcinoma of the bladder and 6 normal controls using an immunohistochemical method on paraffin sections. Positive nuclear staining for p53 in malignant cells was found in 34 (51%) of the 67 cancer patients; no positive staining for p53 was detected in any of the normal controls or in the benign cells, including stromal and inflammatory cells, within the tumor tissue. There were 8 positive cases (33%) in 24 grade G1 tumors, 12 (48%) in 25 G2 tumors and 14 (78%) in 18 G3 tumors. p53 protein was detected positively in 14 (36%) of 39 superficial tumors (Tis-T1) and in 20 (71%) of 28 invasive tumors (T2–T4). Thus, positive staining for p53 was found more frequently in poorly differentiated tumors (chi-squared test: G3/G1+G2P<0.01) and in invasive tumors (chi-squared test: T2–T4/Tis-T1P<0.01). Expression of p53 was also closely associated with recurrence of tumors. Alterations in p53 expression may be of prognostic value in cases of bladder transitional cell carcinoma.     

Prognostic value of E-cadherina, beta catenin, Ki-67 antigen and p53 protein in the superficial bladder tumors

IntroductionThe natural history of the superficial carcinoma of bladder is characterized by his high rate of recurrence and by the aptitude to progress to higher stages. We are going to investigate the capacity of prediction for tumor recurrence of protein p53, antigen Ki-67, E Cadherin and Beta CateninMaterial and method88 t1 tumors with a median of free time of disease of 36 months. 58% of the serie has received prophylactic treatment with bcg 81 mg. weekly for six weeks. cut-oof level for for p53 and ki-67 is 10 % of stained cells. for e cadherin and beta catenin we have established two groups: one with the values 0-4 (negative), and other one with the values 5-8 (positive)ResultsRecurrence rate 31 %, stage progression 3 %. Ki-67 expression is correlated with grade (p.002) and lymphatic permeation (p.028). Multiplicity is correlated with lack( of Cadherin and Catenin´s expression. Only Ki-67 expression (p.049) and lack of Beta Catenin expression (p.039) reach statistical significance. In multivariant study only lack of Beta Catenin’s expression shows independent recurrence value (p.049; O.R: 2,4-6,9)ConclusionsThe most useful prognmostic markers are Ki-67 and Catenina Beta Only Beta Catenin Beta shows independent value for tumour recurrence. Tumors wich lack expression for Catenin B or Cadherin E have lower recurrence free time     

Prognostic study of cell proliferative markers ki67, PCNA and p53 oncoprotein in bladder tumors

We report a study of cell proliferative factors Ki67, PCNA and p53 oncoprotein in 55 patients with bladder tumors. Fifty-three of the patients were male and two were female, with a mean age of 56.6 and 68.5 years, respectively. These tumors were of transitional cell type in 97.9% of the cases. Staging was, respectively, pTis (4.76%), pTa (30.9%), pT1 (19.04%), pT2 (23.8%) and Pt3 (21.4%). Our study of proliferative nuclear markers Ki67 showed that cell proliferation increased in bladder tumors according to grade in the same stage. This variation was highlighted by our results for PCNA but was not verified for Ki67. However, these results revealed an increase of cell proliferation for a same grade (grade I and II) in different stages (pTa, pT1, pT2) for PCNA; this was not ascertained for Ki67. The study of p53 oncoprotein showed that detection of mutated p53 protein increased according to grade only for grades II and III and to stage only when moving from pTis to superficial tumors (pTa, pT1) and to deep tumors (pT2, pT3), thus individualizing two groups without significant variation within these groups. A variation according to grade in the same stage was noted only for stages pT1 and pT2. A variation for a same grade (grades II and III) was reported between stages pTa, pT1 and pT2. The combined study of Ki67, PCNA and p53 oncoprotein showed a prognostic correlation between these three markers in general.