Numeric Aberration of Chromosome 17 Is Strongly Correlated with p53 Overexpression, Tumor Proliferation and Histopathology in Human Bladder Cancer

Background This study investigated the relationships between the numeric aberrations of chromosome 17 and p53 expression, the proliferating cell nuclear antigen labeling index (PCNA-LI) and histopathology, to determine their prognostic significance in bladder cancer.
Methods Using in situ hybridization (1SH) with a biotin-labeled chromosome-specific DNA probe, the copy number of pericentromeric sequences in chromosome 17 were detected within interphase nuclei in formalin-fixed paraffin-embedded sections from 59 nonmetastasized transitional cell carcinomas (TCCs) of the urinary bladder. Expression of p53 and PCNA-LI were determined in serial sections by an immunohistochemical method.
Results The percentage of hyperdiploid cells for chromosome 17 correlated with p53 overexpression (P< 0.002), PCNA-LI (P< 0.002), increasing tumor grade (P< 0.002) and advanced pathologic stage (P< 0.002). The average percentage of hyperdiploid cells was lower in tumors with negative p53 expression than in tumors with p53 overexpression (P< 0.002). Also, more polysomic TCCs were found in muscle-invasive than in superficial cases (P< 0.01), and there was a difference in both p53 overexpression or PCNA-LI between disomic and polysomic TCCs (P<0.01). Patients with chromosome 17 disomic tumors showed less frequent tumor progression than patients with polysomic tumors (P< 0.05). However, chromosome 17 polysomy was an independent prognostic indicator only for patient survival (P< 0.05).
Conclusion The occurrence and extent of numeric aberrations of chromosome 17 may be associated with the evolution of aggressive growth in TCC and may be a useful indicator for survival.     

A clinical study of associated bladder cancer in patients with renal pelvic and ureteral cancer

We reviewed 76 cases of renal pelvic and ureteral cancer, admitted to our hospital between January, 1975 and December, 1988, with special reference to the occurrence of bladder cancer. Bladder cancer was associated with an upper urinary tract neoplasm in 35 of the 76 cases (46.1%), 7 with a preceding bladder cancer, 17 with a coexistent one and 11 with a subsequent one. In case of renal pelvic and upper ureteral cancer the incidence of coexistent or subsequent tumors of the bladder was 28.7% (16 of 56 patients). However, in the cases of lower ureteral cancer the incidence of these tumors was 82.4% (14 of 17 patients). This incidence was significantly higher than that in renal pelvic and upper ureteral cancer. The subsequent bladder cancer was observed in 19 patients including 8 patients who had a recurrence of the bladder cancer after the treatment for a preceding and coexistent bladder cancer. The cancer in most cases occurred within 2 years after the treatment of the upper urinary tract neoplasm. Of 19 patients who had subsequent bladder cancer 11 had primary sites in the renal pelvis and upper ureter. Another 8 patient had primary sites in the lower ureter. Four of the 8 subsequent bladder cancers in patients with lower ureteral cancer occurred just on and around the affected ureteral orifice. All these 4 tumors were high grade and high stage tumors. On the other hand, another 15 patients developed subsequent bladder cancer in a place other than the affected ureteral orifice. Of these 15 patients, 13 cases showed a low grade and low stage tumor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic values of p53 and HER-2/neu coexpression in invasive bladder cancer in Taiwan

OBJECTIVES: To explore the clinical significance of p53 and HER-2/neu coexpression by immunohistochemistry in patients with invasive bladder cancer in Taiwan. METHODS: Paraffin-embedded tumor blocks were obtained from 67 patients with invasive bladder cancer subjected to radical cystectomy, bilateral lymph node dissection, and urinary diversion with or without systemic chemotherapy. Two observers (N.H.C. and T.S.T.), blinded to clinical outcome, reviewed the immunohistochemical staining for p53 (PAb1801) and HER-2/neu (Ab-17). The results were analyzed for progression-free survival and patient survival. RESULTS: Positive staining for p53 and HER-2/neu was found in 30 (44.8%) and 39 (58.2%) patients. In contrast to HER-2/neu, p53 expression was significantly associated with tumor grade and pathologic stage (p = 0.040 and 0.004, respectively), and tended to be related to the nodal status (p = 0.080). Most importantly, coexpression of p53 and HER-2/neu significantly correlated with nodal metastases (p = 0.020). Univariate and multivariate analysis revealed p53 and nodal status as two independent prognostic factors. Additionally, patients with p53 and HER-2/neu coexpression had the shortest time to relapse and overall survival, irrespective of whether adjuvant chemotherapy was given or not (p = 0.005 and 0.030). CONCLUSIONS: In invasive bladder cancer, p53 was an important prognostic factor since its expression correlated with tumor grade and stage, even nodal status, whereas HER-2/neu did not show prognostic significance. Tumors with p53 and HER-2/neu coexpression were associated with nodal metastases, probably resulting in decreased progression-free survival. Although some basic studies provide some important supports, studies including larger patient cohorts would still be required to prove the hypothesis that p53 and HER-2/neu-coexpressing tumors have a worse prognosis and are more resistant to a cisplatin-based multidrug regimen.     

Risk factors for the development of bladder cancer after upper tract urothelial cancer

OBJECTIVES: To determine the clinical and pathologic risk factors for initial intravesical recurrence in patients with primary renal pelvic and/or ureteral cancer and to examine the progression in the bladder in patients having high risk factors for intravesical recurrence. METHODS: This study included 69 patients with renal pelvic and/or ureteral cancer. We excluded patients with distant metastases, those with a short period of follow-up, and those having a previous history or concomitance of bladder cancer. The exclusion criteria were chosen to avoid contamination by patients with a poor prognosis who might die of the primary cancer before bladder cancer development. Multivariate analysis by Cox's proportional hazards model was used to determine what clinical and pathologic variables significantly affected the initial intravesical recurrence of cancer. We also studied the stage progression of cancer that recurred in the bladder. RESULTS: Initial intravesical recurrence of the cancer was found in 22 patients during a median follow-up period of 53 months (range 12 to 225). The intravesical disease-free rate after upper tract urothelial cancer was 65% (rate of disease recurrence in bladder 35%) at 5 years by the Kaplan-Meier method. The extent (multifocality) of the upper urinary cancer (P = 0.0038) and pathologic stage (P = 0.0409) independently influenced intravesical recurrence. Age, sex, adjuvant chemotherapy, configuration of the primary tumor, primary cancer size, and pathologic grade did not affect recurrence. The rate of stage progression also was not influenced by the extent of the disease in the upper urinary tract. CONCLUSIONS: The extent and pathologic stage of cancer in the upper urinary tract were significant and independent factors for initial intravesical recurrence of cancer. However, no difference was found in clinical outcome in terms of stage progression between patients having high risk factors for intravesical recurrence and those without them.     

A comparison of the pathology of transitional cell carcinoma of the bladder and upper urinary tract

OBJECTIVE: To clarify the histopathological patterns of upper and lower urinary tract transitional cell carcinomas (TCCs), as previous reports suggest that upper urinary tract TCCs have a greater tendency towards high-grade disease than bladder TCCs, of which most are low-grade and low-stage tumours. PATIENTS AND METHODS: All patients presenting with TCC of bladder or upper urinary tract between February 1991 and December 2001 at one institution were identified. Further patient information was obtained from the hospital database and case-note review. RESULTS: In all, 164 patients with upper urinary tract TCC and 2197 with bladder TCC were identified. There was a correlation between grade and stage of both upper urinary tract and bladder TCCs. 35% of the upper tract TCCs were classified as grade 2 and 44% as grade 3, while for bladder TCCs, 31% of lesions were classified as grade 2 and 35% as grade 3 (P = 0.003). Of the upper urinary tract lesions 33% were stage pT2-T4, compared with only 20% of bladder TCCs (P = 0.001). CONCLUSIONS: Upper urinary tract TCC is a higher grade and stage disease than bladder cancer, a finding that emphasizes the need for aggressive treatment of upper urinary tract TCC. If endourological management of upper urinary tract TCC is considered, histopathological determination of tumour grade before treatment is essential.     

Allelic loss of chromosome 17p in urothelial cancer: strong association with invasive phenotype.

Allelic loss of chromosome 17p with a mutated p53 gene on the remaining allele has been observed in various kinds of human cancers. To examine the significance of allelic loss of chromosome 17p in human urothelial cancer with special attention to the clinicopathological features, 49 tumors with various stages and grades from 43 cases (35 bladder cancers and 8 renal pelvic or ureteral cancers) were examined for loss of heterozygosity using 5 polymorphic probes on chromosome 17p. Thirty-seven cases were informative, and allelic loss of chromosome 17p was observed in 15 (41%) of them. In bladder cancers, the loss of 17p was observed with significantly higher frequency (p < 0.01) in cases with invasive (> or = pT2) tumors (7/10, 70%) than in cases with superficial (pTa or pT1) tumors (4/21, 19%). In renal pelvic or ureteral cancers, none of 2 superficial tumors and all of 4 invasive tumors showed the allelic loss. As to tumor grade, the allelic loss was observed in 1/9 (11%) for grade 1 cases, 6/18 (33%) for grade 2 cases, and 8/10 (80%) grade 3 cases (grade 1 versus 3, p < 0.01; grade 2 versus 3, p < 0.05). On the other hand, examination of clinical features, such as primary tumor site, tumor multiplicity or previous history of urothelial cancer did not significantly influence the frequency of the allelic loss. Our results suggest that the allelic loss of chromosome 17p is strongly associated with invasive phenotype in urothelial cancer. The results further indicate that the 17p deletion may represent a new genetic marker of malignant potentials in urothelial cancers.     

Correlation between the expression of P-glycoprotein and multidrug-resistant phenotype in transitional cell carcinoma of the urinary tract.

The expression of a multidrug-resistant (MDR) gene product, P-glycoprotein, was examined immunohistochemically in 41 transitional cell carcinomas (TCCs) of the urinary tract. In 23 of these, chemosensitivity to adriamycin (ADM) and vinblastine (VBL) was also assessed by a microtiter succinate dehydrogenase inhibition test and the correlation between the expression of P-glycoprotein and MDR phenotype was investigated. P-glycoprotein was detected in 13 (72.2%) of the 18 untreated TCCs of the upper urinary tract (UUT), 6 (31.6%) of the 19 untreated TCCs of the bladder, and all of the 4 TCCs treated with M-VAC chemotherapy, respectively. Fourteen (87.5%) of the 16 TCCs with a positive expression of P-glycoprotein were resistant to ADM and VBL, whereas all of the 4 TCCs sensitive to both drugs were negative in the expression of P-glycoprotein. The succinate dehydrogenase activity of TCCs with a positive expression of P-glycoprotein was significantly higher than that of TCCs with a negative expression of P-glycoprotein (P < 0.05). Thus, there was a good correlation between the expression of P-glycoprotein and MDR phenotype in the chemosensitivity test. These results suggest that intrinsic MDR exists in some TCCs of the urinary tract, particularly UUT, and that the immunohistochemical investigation of P-glycoprotein may be useful for predicting the MDR phenotype in TCCs of the urinary tract.     

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。     

Evaluation of urinary cytology for upper urinary tract disease

One hundred and seventy-two patients with upper urinary tract disease were examined by cytological study of ureteral urine which was taken by ureteral catheterization. Of 139 patients with benign disease or ureteral stricture due to non-urological cancer, only one case with renal cyst revealed positive findings (false positive rate: 0.7%). Two positive cases, which were a renal hemorrhage without followup and a uterine cervical cancer with squamous cancer cells in the ureteral urine, were excluded. Although 6 of 17 (35%) uroepithelial cancers in the upper urinary tract were registered as positive, this examination was little use for detecting stage pTa, grade 1 or papillary non-invasive tumors. However, 2 out of 12 (17%) renal pelvic or ureteral cancer patients with negative results of voided urine were cytologically detected by ureteral urine. Five out of 6 cases of these cancers demonstrated malignant cells in the renal pelvic urine sampled from surgical specimen. We have recently experienced aspiration cytology for upper urinary tract disease, using the percutaneous puncture method, and five of 7 upper urinary tract patients were cytologically diagnosed. This procedure could be valuable for detecting even patients with associated bladder cancer or failure of ureteral catheterization.     

p53和Ki-67基因表达与膀胱癌分级、分期相关性的大样本回顾性研究

目的:探讨p53和Ki-67基因表达与膀胱癌病理分级和临床分期的关系。方法:回顾性分析2013年1月至2015年1月在本院与天津医科大学第二医院收治的445例膀胱癌患者的临床资料,应用免疫组织化学染色的方法,对这些膀胱癌患者的病理切片进行p53和Ki-67免疫组化染色,并将p53和Ki-67基因的免疫组化表达强度结果与...     

肾盂输尿管癌多药耐药与蛋白激酶C的相关性研究

目的探讨蛋白激酶C与肾盂输尿管癌多药耐药(MDR)的相关性。方法采用免疫组织化学卵白素生物素过氧化物酶连接法(SABC)对45例肾盂输尿管癌蛋白激酶C(PKC)、多药耐药膜糖蛋白表达进行对比研究。结果肾盂输尿管癌蛋白激酶C阳性表达率为60.0%(27/45),多药耐药膜糖蛋白阳性表达率为62.2%(28/45)。肾盂输尿管癌蛋白激酶C、多药耐药膜糖蛋白表达T     

Serum anti-p53 antibodies and p53 protein status in the sera and tumors from bladder cancer patients

OBJECTIVES: The purpose of this study was to evaluate the association between the serum anti-p53 antibodies (Abs) status and the p53 protein status in the sera and tumors as well as clinical or pathological parameters in bladder cancer patients retrospectively. METHODS: Serum samples from 100 patients with bladder cancer were assayed for anti-p53 Abs and p53 protein by enzyme-linked immunosorbent assay (ELISA). A monoclonal antibody DO7 was used for immunohistochemical staining of tumor p53 protein. RESULTS: Prevalences of serum anti-p53 Abs, serum p53 protein and tumor p53 protein were 12, 1 and 63%, respectively. There was a significant correlation between serum anti-p53 Abs status and factors including tumor stage, tumor grade, and tumor p53 protein status. In the univariate analysis, tumor stage, tumor grade, serum anti-p53 Abs status, and tumor p53 protein status were significantly associated with an increased risk of death. Multivariate analysis showed that tumor stage was the only independent prognostic factor among the factors examined. CONCLUSIONS: The present study suggests that serum anti-p53 Abs had a limited value as a tumor marker in bladder cancer patients. Further studies to elucidate the mechanism of anti-p53 Abs production will be necessary for a better understanding of the immune status in bladder cancer patients.     

抑癌基因P53及其蛋白产物表达与膀胱癌发生及病理关系

以光敏生物素－金标链亲和素核酸原位杂交及免疫组化方法检测膀胱癌病理标本中Ｐ５３基因片段及其蛋白表达。１３例原位杂交阳性膀胱癌中，Ｐ５３蛋白表达阳性率５３．９％，提示约半数膀胱癌的发生可能与Ｐ５３基因突变有关；Ｐ５３蛋白表达与病理分级、临床分期无明显关系。     

The study on cell surface antigens in epithelial tumor of the upper urinary tract: ABH-isoantigen and Thomsen-Friedenreich antigen

ABH-isoantigen (ABH-Ag) and Thomsen-Friedenreich antigen (T-Ag) were investigated by the Avidin-Biotin-Peroxidase Complex (ABC) method on 47 patients with epithelial tumor of the upper urinary tract (all patients underwent nephroureterectomy including the cuff of the bladder; 30 patients were diagnosed as transitional cell carcinoma of renal pelvis and 17 ureteral organs). The correlations between ABC expression for ABH-Ag and T-Ag with histological grade, stage and prognosis (5 year survival rate) were studied. A correlation was observed between grade (p less than 0.05) and deletion of the antigenicity of ABH-Ag, but no correlation was evident with stage and prognosis. A high correlation was evident, however, between grade (p less than 0.01), stage (p less than 0.01) and prognosis (p less than 0.01) and deletion of the antigenicity of T-Ag. The analysis of ABC expression for ABH-Ag and T-Ag may therefore be valuable for predicting the malignant potential in transitional cell carcinoma of the upper urinary tract. T-Ag determination in particular may provide a useful prognostic probe should it find clinical application.     

A clinical survey of renal pelvic and ureteral tumors associated with bladder tumor

A clinical survey was performed on 80 cases of renal pelvic and ureteral transitional cell carcinomas we treated between January, 1963 and December, 1986. The cases included 30 of renal pelvic tumors, 17 of ureteral tumors, 3 of renal pelvic and ureteral tumors, 7 of renal pelvic and ureteral and bladder tumors, 16 of ureteral and bladder tumors and 7 of renal pelvic or ureteral tumors after treatment for bladder tumors. There were 37 cases of bladder tumors: 7 cases with preceding bladder tumors, 23 cases of synchronous bladder tumors, and 13 cases of subsequent bladder tumors. The 5-year survival for all cases was 60.2%. The 5-year survival for 43 cases unrelated with bladder tumors was 80.5% and that for 37 cases of bladder tumor was 41.6%. Therefore, there was a significant difference between these 2 groups (p less than 0.005). The 5-year survival for 50 cases without synchronous bladder tumors at first diagnosis was significantly higher than that for 23 cases with synchronous bladder tumors (p less than 0.001). Subsequent bladder tumors occurred after 2 to 48 months (mean 10 months) of the initial treatment for renal pelvic and ureteral tumors. Six of the 7 cases of preceeding bladder tumors were superficial tumors of pTa and pT1 and 3 cases had vesicoureteral reflux.     

The prevalence and clinicopathologic correlate of p16INK4a, retinoblastoma and p53 immunoreactivity in locally advanced urinary bladder cancer

The purpose of the study was to investigate the prognostic value and clinicopathological correlate of tumor p53, p16 and Rb protein expression in patients with locally advanced urinary bladder cancer. Sixty-five patients (44 men and 21 women; 40 to 84 yrs old) with locally advanced urinary bladder cancer (21 pT2, 27pT3, 17pT4) undergoing radical cystectomy and bilateral pelvic lymph node dissection were followed up for 2 to 116 months (mean +/- SD: 30.02 +/- 6.46 months). Immunohistochemical staining for p53, Rb and p16 proteins were performed on surgically obtained, formalin fixed and paraffin embedded tissue sections. Thirty of the tumors (46.2%) were p53+, 52 of the tumors (80%) were p16- and 41 (63%) were Rb-. Only 5 of the tumors (7.7%) had normal expression of all three proteins. The tumor expression status of p53 could not be correlated with p16 (P = 1.000) or Rb (P = 1.000). Only a marginal inverse relationship was found between the expression of p16 and Rb (P = 0.056). Higher grade tumors had significantly lower percentage of p16 abnormality (P = 0.05), while higher grade (not higher stage) tumors had higher percentage of Rb abnormality (P = 0.0245). Univariate analysis showed that tumor expression of Rb or p16, alone or combined, had no predictive value on progression-free and disease-specific survival. It did, however, show a significant correlation between progression-free survival and tumor p53 and LN status (P = 0.032 and P = 0.0304) and a significant correlation between tumor stage disease-specific survival (P = 0.042). Multivariate analysis showed tumor stage and nodal status to be two significant independent indicators for progression-free survival (P = 0.0038 and P = 0.0049) and disease-specific survival (P = 0.0066 and P = 0.0484). It was also noteworthy that, after receiving postoperative adjuvant systemic M-VEC chemotherapy, patients with node-positive p53-normal tumors had significantly better progression-free and disease-specific survivals than those with node-positive p53-abnormal tumors (P = 0.036 and P = 0.0479, respectively). This study has found tumor expression of p53, p16 and Rb proteins in locally advanced bladder cancer to be frequently abnormal. Although multivariate analysis showed tumor stage and nodal status to be the only two statistically significant parameters, p53 may also serve as an additional prognostic predictor of the outcome of postoperative adjuvant systemic chemotherapy in patients with regional lymph node tumor involvement. Such patients with p53-normal tumors experienced significantly better progression-free and disease-specific survivals than those with p53-abnormal tumors.     

Heparanase protein and gene expression in bladder cancer

PURPOSE: We determined the association of heparanase protein and messenger (m)RNA expression with bladder cancer invasion and metastasis. MATERIALS AND METHODS: The expression of heparanase protein and mRNA was assessed by immunohistochemical staining and in situ hybridization, respectively, in 67 bladder cancer specimens resected at various stages of disease. To our knowledge this is the first systematic study of heparanase protein and mRNA expression in human bladder cancer. RESULTS: The expression of heparanase protein in muscular invasive bladder cancer was significantly higher than in superficial cancer (68% versus 19%, p = 0.0001). It was higher in the primary tumor of patients with lymph node metastatic cancer than those with nonmetastatic cancer (80% versus 37%, p = 0.0006). In high grade disease it was significantly higher than in low grade disease (79% versus 29%, p = 0.0001). The expression of heparanase mRNA was also significantly higher in stage pT3 or greater than in stage pT2 or less bladder cancer (96% versus 33%, p = 0.0003). In metastatic N+ cases it was significantly higher than in nonmetastatic bladder cancer (93% versus 46%, p = 0.0037). The heparanase gene and protein showed similar patterns of expression in bladder cancer. CONCLUSIONS: Our study implies that the expression of heparanase protein and mRNA is associated with bladder cancer invasion and metastasis, and heparanase may have a role in disease progression.     

Immunohistochemical study of p53 and Ki-67 antigen expression in bladder carcinoma]

We examined the relationship between the expression of mutant p53 and Ki-67 antigens in urinary bladder transitional cell carcinoma and the pathological and clinical findings. Tissues were obtained from 28 patients with bladder carcinoma who underwent total or partial cystectomy. An ABC immunostaining method and two primary antibodies (DO-7 and MIB-1 antibodies) were used. The percentages of p53 and Ki-67 antigen-positive cells to the total number of cells were regarded as the p53 and Ki-67 labeling indices (LI) respectively. There were no statistically significant correlations between p53 LI and the histological grade or stage, although p53 LI increased slightly in the high grade and high stage group. There was a statistically significant correlation between Ki-67 LI and the histological grade and stage (p < 0.05). The correlation between p53 LI and Ki-67 LI was linear. Some cases had a p53 LI below the mean even though the Ki-67 LI was higher. The clinical course was characteristic of superficial bladder carcinoma initially, but progressed to invasive bladder carcinoma over the next several years. These results suggest that even cases initially diagnosed as superficial bladder carcinoma with a low p53 LI may progress to invasive bladder carcinoma in subsequent years. Therefore, it is important that the patient be followed-up.     

The correlation of p53 protein overexpression and p53 antibodies in serum of patients with transitional cell carcinoma of the urinary bladder

BACKGROUND: Mutations of p53 gene were demonstrated in many solid tumors with varying frequency. We analyzed the relationship between p53 protein expression in bladder cancer tissue, p53 autoantibodies in serum and the clinical course of 32 patients with and 10 patients without transitional cell carcinoma of the urinary bladder. MATERIALS AND METHODS: In the 32 patients studied, bladder cancer was diagnosed as pTaG1-2 in 8 cases, pT1G2 in 6, pT1G3 in 7, pT2G2-3 in 7, pT3G2-3 in 3 and pT4 in 1 patient. Anti-p53 antibodies were detected by an enzyme-linked immunosorbent assay. Immunohistochemical staining was performed using a standardized alkaline phosphatase monoclonal anti-alkaline phosphatase method. To prove the statistical significance of tumor grading and staging, the Kruskal-Wallis test was applied (p < 0.01). The mean follow-up was 26 months. RESULTS: We found 12.5% p53 autoantibody-positive sera without a statistically significant correlation with tumor grade (p = 0.0569) and category (p = 0.612). Three of 4 patients who had p53 autoantibody-positive sera died within 9 months. All of these sera-positive patients had p53 protein-positive tumor tissue. Control sera were all negative for p53 autoantibodies. CONCLUSION: This study shows a strong relationship between p53 protein overexpression and the occurrence of p53 autoantibody in bladder cancer. The expression of p53 autoantibodies seems to be an event in cases of bladder cancer with an unfavorable tumor-specific outcome. Because of the small number of cases and the short follow-up time, further quantitative studies will hopefully demonstrate whether this might be of prognostic importance.     

Expression of cell cycle regulators, 14-3-3σ and p53 proteins,and vimentin in canine transitional cell carcinoma of the urinary bladder

ObjectivesThe study of the expression of 14-3-3σ, p53, and vimentin proteins in canine transitional cell carcinoma (TCC) evaluating differences with normal bladder tissues, and the association with clinicopathological variables.MethodsWe analyze by immunohistochemistry in 19 canine TCCs the expression of 14-3-3σ, p53, and vimentin using monoclonal antibodys. A semiquantitative scoring method was employed and statistical analysis was performed to display relationships between variables.ResultsIn contrast to normal urinary bladder epithelium, which showed high levels of 14-3-3σ, its expression was decreased in 53% of the studied tumors (P = 0.0344). The 14-3-3σ protein was expressed by neoplastic emboli and by highly infiltrative neoplastic cells. The p53 protein was expressed in 26% of TCCs, but no significant association between 14-3-3σ and p53 was detected. Neoplastic epithelial cells displayed vimentin immunoreactivity in 21% of TCCs, and a positive correlation with mitotic index was observed (P = 0.042). Coexpression of vimentin and 14-3-3σ by highly infiltrative neoplastic cells was also observed.Conclusions14-3-3σ is deregulated in canine TCCs and its expression by highly infiltrative tumor cells may be related to the acquisition of aggressive behavior. Furthermore, this article reinforce the role of canine TCC as relevant model of human urothelial carcinoma and we suggest 14-3-3σ as a potential therapeutic target. Further studies are necessary to clarify the role of 14-3-3σ in canine TCC.