Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent molecular studies on transitional cell carcinomas (TCC) of the urinary bladder suggest two genetically different tumor types with a varying degree of genomic instability-pTa (grade 1 and 2) tumors are usually "genetically stable". These tumors have rarely p53 alterations and contain only few genomic alterations (deletions, DNA sequence copy number gains, amplifications). Genomic changes in these tumors typically include losses of the chromosomes Y and 9 as well as 1q gains. TCC's with invasive growth pattern (pT1-4) are mostly "genetically instable". They have p53 alterations in about 50% of tumors, and often numerous DNA sequence copy number changes including deletions of 2q, 5q, 6q, 8p and 11p as well as gains at 1q, 3p, 3q, 5p, 6p, 8q und 10p. High level amplifications at various sites of the genome are also frequent in these "instable tumors". They may pinpoint the localization of overexpressed oncogenes. Further studies will have to investigate whether genetic analyses can add useful information to the currently used pathological (pTNM) and clinical (superficial/invasive) classifications of urinary bladder cancer.
 ...
PMID:[Genomic changes in urinary bladder cancer]. 947 82

The inhibitor of cyclin-dependent kinases WAF1/p21 has been shown to mediate cell cycle arrest by p53 and other factors. We have studied its expression in urothelial carcinoma. Immunohistochemistry of paraffin-embedded tissues revealed no detectable p21 protein in normal mucosa, whereas 8 of 17 (47%) carcinomata in situ, 41 of 62 (66%) pTa, 14 of 30 (47%) pT1 and 5 of 15 (33%) muscle-invasive tumours stained positive, usually with a heterogeneous pattern. Expression of p21 was associated with low grade tumours. In contrast, the frequency of p53 accumulation increased with grade and stage as did the frequency of staining for the proliferation marker Ki67. The level of WAF1 mRNA was determined relative to beta-actin mRNA by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 15 freshly frozen invasive tumours. In eight samples obtained from normal bladder mucosa, the values ranged from 0.93 to 2.19 arbitrary units (AU) (mean 1.54+/-0.37 AU), but varied widely from non-detectable to 16.21 AU (mean 3.02+/-4.44 AU) in the tumour specimens. In accord with the immunohistochemical findings, WAF1 mRNA expression was elevated over the range found in normal mucosa in 5 of 15 advanced tumours. In addition, RNA analysis revealed a decrease in expression in six tumours. No mutations were observed in the WAF1/p21 gene in these tumours, but two were heterozygous for the codon 31 polymorphism. These data indicate that p21 is frequently expressed in superficial, well differentiated urothelial carcinomas, but less often in muscle-invasive urothelial carcinomas, irrespective of their p53 status. The expression of p21 and its prevalence in low-stage tumours may reflect residual growth-regulatory influences potentially impeding but not necessarily inhibiting tumour development.
 ...
PMID:Frequent and heterogeneous expression of cyclin-dependent kinase inhibitor WAF1/p21 protein and mRNA in urothelial carcinoma. 948 5

Expression of p53 and MiB1, markers of tumor proliferation, was evaluated in human bladder tumors, and correlated with ploidy and cancer progression in 83 consecutive patients. Transurethral resection of a newly diagnosed bladder tumor was performed in 73 cases, and systematic bladder biopsies were performed in 10 cases after bacillus Calmette-Guerin (BCG) treatment. p53 and MiB1 expression were performed by an immunohistochemical technique and the ploidy was determined on a frozen fragment of the tumor. p53 expression was correlated in relation to grade, stage and combination of grade and stage. MiB1 expression was correlated with cytological grade, and a significant difference was demonstrated between pT0 and pTa, pTa, and pT1, pTa and pT2 tumors but not between pT1 and > or = pT2 tumors. A discordance was observed for the comparison of p53 and MiB1 values, stage by stage, suggesting that these two techniques are independent of each other. A larger proportion of aneuploid tumors were positive for p53 and MiB1 (64.8 vs. 86.5%, respectively), but p53 and MiB1 immunostaining were not better indicators than ploidy alone to predict cancer progression.
 ...
PMID:Comparative analysis of MiB1 and p53 expression in human bladder tumors and their correlation with cancer progression. 955 52

The histological background for multifocal and metachronous development of urothelial carcinomas remains equivocal, although accumulated genetic evidence suggests monoclonal origin of multiple urothelial carcinomas. Clonal development of various preneoplastic and neoplastic urothelial lesions of C3H<-->BALB/c chimeric mice induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was immunohistochemically investigated using a C3H strain-specific antibody. All tumor masses induced in the mice treated with 0.05% BBN for 20 weeks were composed of neoplastic cells of a single parental type, which is indicative of monoclonal lesions. Three of 10 animals harbored two or more separate carcinomas of different clonal type, which is indicative of multicentric development applicable in this model. Using DNAs derived from urothelial carcinomas and tumor-adjacent urothelium of chimeric mice, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing were performed for p53 gene exons 5-7. p53 mutations were identified in four of 11 (36%) dysplasias and non-invasive carcinomas (carcinoma in situ and pTa tumor) and 13 of 22 (59%) invasive carcinomas. Only in a single case were identical p53 mutations found in separate urinary bladder carcinomas. In contrast to the random distribution of urothelial proliferating units in chimeric mice without chemical supplement, invasive carcinomas in BBN-treated mice were accompanied by widely-distributed preneoplastic and neoplastic lesions of the same clonality, which occasionally had frequent foci of microinvasion. This is indicative of lateral clonal expansion of the clones, which precedes the bulk of invasive carcinomas. Thus, two aspects of 'field change' of the urothelium became evident in this model: either independent transformation events or lateral clonal expansion might, respectively, result in multicentric and monoclonal carcinoma development in the urinary tract.
 ...
PMID:Clonal analysis of urothelial carcinomas in C3H/HeN<-->BALB/c chimeric mice treated with N-butyl-N-(4-hydroxybutyl)nitrosamine. 963 74

Detection of urinary telomerase activity is superior to the conventional urine cytological examination in terms of sensitivity for diagnosis of low grade urothelial cancers. Several causative factors including pyuria and hematuria which might have affected falsely positive and negative rates of urinary telomerase activity were investigated but their influence seemed negligible. As for progression from superficial to invasive urothelial cancers, destruction of the basement membrane underlying tumor is considered as an important event in the initial step of invasion. Our immunohistochemical analyses revealed that expression of type IV collagen in the basement membrane was reduced or disappeared in more than half of grade 2 to 3, pTa urothelial cancers. Overexpression of p53 tumor suppressor and/or mdm2 oncoprotein was strongly correlated with this basement membrane destruction. Urothelial cancers harboring p53 aberration may be resistant to cisplatin-based chemotherapy because of impairment of apoptosis induction. The relationship between chemosensitivity and p53 status in urothelial cancers was investigated, and a favorable response to neoadjuvant chemotherapy was found in tumors without p53 aberration.
 ...
PMID:[Molecular biological testing for diagnosis and treatment of urothelial cancer]. 1050 Sep 67

The aim of the study was to determine whether the expression of the cell cycle markers p53, MDM2, p21, and Ki-67 was predictive of superficial bladder cancer recurrence and to compare the relative predictive power for tumor recurrence of a cell cycle index based on the number of abnormally expressed cell cycle markers with a clinicopathological index based on primary clinical tumor characteristics. The expression of p53, MDM2, and p21 proteins and the value of the Ki-67 index were analyzed for 244 patients. One hundred ninety-four lesions were determined to be superficial papillary tumors (pTa), whereas 50 tumors invaded the lamina propria (pT1). Tumor grade was noted low (grade 1) in 83 cases and high (grades 2-3) in 161 cases. An avidin-biotin peroxidase method was performed using monoclonal antibodies against p53, MDM2, p21, and Ki-67 antigens after antigen retrieval treatment of formalin-fixed specimens. The cell cycle marker index was created using the number of abnormally expressed cell cycle markers according to the following cutoff points: p53 (>5%), MDM2 (>20%), p21 (<5%), and Ki-67 (>10%). The clinicopathological index was created using the following adverse tumor characteristics: grades G2-G3, stage pT1, multifocality, and diameter of tumors > 3 cm. Cox regression models were used to calculate the relative risks and their 95% confidence intervals associated with disease recurrence for the clinicopathological index and the cell cycle marker index. The chi2 test was performed to describe the correlation between the Ki-67 index and p53, MDM2, and p21 protein expression. Kaplan-Meier survival curves were generated to demonstrate the disease-free survival according to these two prognostic indexes. The clinicopathological index was a strong, independent predictor of disease recurrence where tumors with three or four adverse tumor characteristics at initial resection had over four times the risk of recurrence than tumors with no risk factors (P for trend = 0.0001). A strong correlation was observed between the Ki-67 index >10% and both MDM2 and p21 proteins. MDM2 was overexpressed in 106 tumors (43%), and p53 was overexpressed in 47 (19%); Ki-67 was >10% in 171 cases (70%). Thirty-nine tumors (16%) were p21 negative. The risk of recurrence increased slightly with the number of abnormally expressed cell cycle markers, but when the clinicopathological index was taken into account in multivariate analysis, the cell cycle marker index was not predictive of disease recurrence (P for trend = 0.72). The cell cycle markers studied provided no added prognostic information on disease recurrence after initial resection of papillary superficial tumors when the clinicopathological parameters were taken into account.
 ...
PMID:Predictive value of cell cycle markers p53, MDM2, p21, and Ki-67 in superficial bladder tumor recurrence. 1600 76

Our aim was to determine whether the pattern of expression of the interrelated proteins p53, MDM2 and p21 could shed light on the etiopathogenic mechanisms of superficial bladder tumors. Protein expression was detected by immunohistochemistry (IHC) using monoclonal antibodies (MAbs) Pab 1801 for p53, IF2 for MDM2 and EA10 for p21 on 269 newly diagnosed bladder tumors (214 pTa and 55 pT1; 93 grade I, 145 grade 2 and 31 grade 3). While no p21 immunoreactivity was found in normal urothelium, 85% of tumors were strongly p21-positive. MDM2 was overexpressed in 44% of tumors, almost all being also positive for p21. p53 was overexpressed in 20% of cases: 66% of p53-positive tumors were also MDM2 positive, compared with only 38% of p53-negative tumors. p53 mutations were studied by direct DNA sequencing in a subset of 24 high-grade tumors. Both MDM2 and p21 were less frequently expressed in p53 mutated tumors compared with tumors with a wild-type gene. Distinct phenotypes were correlated with the frequency of poorly differentiated (grade 3) tumors. The most common phenotypes were p21+/MDM2-/p53- and p21+/MDM2+/p53- observed in 38% and 29% of tumors, respectively. Grade 3 tumors were found in 4% and 8% of these 2 groups, in contrast with 30% frequency in p21+/p53+ tumors (p = 0.002) regardless of their MDM2 phenotype. Four of the 5 (80%) tumors that were p53-positive but negative for p21 were grade 3. Our data suggest that several tumorigenic pathways for superficial bladder tumors can be reflected by the expression pattern of these 3 proteins.
 ...
PMID:Tumorigenic pathways in low-stage bladder cancer based on p53, MDM2 and p21 phenotypes. 1071 38

Superficial transitional cell carcinoma of the bladder (STCCB) is a heterogeneous group of neoplasias with an unpredictable clinical course. In recent years many techniques have been used in order to predict the behaviour of these tumours at individual patient level. The aim of this study was to investigate in imprints from tumour biopsies the DNA ploidy and p53 protein expression in a group of 80 STCCB (pTa-pT1) patients in relation to histological grade and recurrence status. The DNA content was studied in Feulgen-stained imprints by the image analysis technique using a SAMBA 2005 analyser. In order to investigate p53 protein expression an avidin-extravidin immunocytochemical technique was used. According to our measurements a strong correlation was observed between recurrence status and DNA ploidy status (P < 0.001). No statistical difference was found in DNA ploidy status and grade of malignancy (P = 0.68). A statistically significant difference was found in p53 protein expression between recurrent and nonrecurrent tumours (P < 0.001). No statistically significant difference was found among tumours of grade I, grade II and grade III (P = 0.42). These results could provide useful information on the potential behaviour of STCCB.
 ...
PMID:DNA ploidy and p53 protein expression in superficial transitional cell carcinoma of the bladder. 1077 9

The clinical value of p21WAF1/CIP1 in superficial bladder cancer remains controversial. To address the question, we examined the expression patterns of p21 and p53 gene products and compared for their significance in a total of 89 cases of superficial (pTa/pT1) bladder cancer. Over-expression of p21 was detected in 32 of 89 (36%) tumors. But, the expression status did not correlate with biological indicators or clinical outcome (p > 0.1, respectively). Factors predicting clinical outcome were multiplicity for tumor recurrence (p = 0.0002) or patient survival (p = 0.03), and the histological grading for disease progression (p = 0.02) or patient survival (p = 0.05). Taking into account the p53 status, a trend approaching better prognosis for p53+p21+ tumors was observed compared with that of p53+p21- bladder cancer (p = 0.08). Our data indicate that evaluation of p21 status does not provide better prognostic information compared with conventional biological indicators of superficial bladder cancer. Maintenance of p21 appears to abrogate the deleterious effects of p53 alterations in the tumorigenesis of human bladder.
 ...
PMID:The clinical value of p21WAF1/CIP1 expression in superficial bladder cancer. 1081 Apr 17

p21Waf1 is a downstream effector of p53 and belongs to the Cip1/Kip1 family of cyclin-dependent kinase inhibitors. Thus, it is a potential tumor suppressor gene and likely plays an important role in tumor development. Moreover, reduced expression of p21Waf1 has been reported to have prognostic value in several human malignancies. In this study, we evaluated the prognostic value of p21Waf1 in bladder cancer compared with other clinicopathological features and with p27Kip1 and p53 expression. A total of 96 superficial (pTa-1) human bladder carcinomas were immunohistochemically stained for p21Waf1 protein expression. Positive p21Waf1 staining (> or =5% positive nuclei) was observed in 68 of the 96 (71%) tumors. p21Waf1 expression was neither associated with tumor stage (P = 0.9) nor with tumor grade (P = 0.18) but was significantly associated with both p53 protein expression (> or =20% positive nuclei; P = 0.007) and with p53 gene mutations (P = 0.017). A significant correlation was also observed between positivity for p21Waf1 and high (>50% positive cells) p27Kip1 expression (P = 0.04). With regard to prognosis, patients whose tumors showed absence of p21Waf1 staining displayed a significantly shorter overall survival (P = 0.01 by log-rank test). However, p21Waf1 expression did not correlate with disease-free survival (P = 0.15 by log-rank test). On a multivariate analysis that also included p53 and p27Kip1 expression, negative p21Waf1 staining was an independent predictor of reduced overall survival (P = 0.004; relative risk, 5.32), stronger than age and tumor stage. These data indicate that expression of p21Waf1 protein strongly correlates with survival and might represent a useful prognostic marker in primary superficial bladder carcinomas.
 ...
PMID:Loss of p21Waf1 expression is a strong predictor of reduced survival in primary superficial bladder cancers. 1095 94


<< Previous 1 2 3 4 5 Next >>