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

Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.
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PMID:Two molecular pathways to transitional cell carcinoma of the bladder. 830 42

Bladder cancers display different forms from superficial to aggressive tumours with muscle invasion. Many studies on this disease have been carried out in order to better understand the molecular mechanisms involved in its progression. Two loci are frequently associated with bladder tumorigenesis. The chromosome 9 lesions seem to be earlier involved in carcinogenesis, and suggest the presence of a tumour suppressor gene, and on the other hand the TP53 gene mutations (17q13.1) are later but take place in tumour progression. These alterations could be used as early diagnosis tool in bladder tumours and orientate the search for the bladder cancer gatekeeper gene(s).
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PMID:[Tracking the gatekeeper gene in the stages of carcinogenesis in the bladder]. 943 99

Mutations in the tumor suppressor gene p53, analyzed in bladder washings, have positive predictive value for the progression of superficial bladder cancer to invasive disease. Bladder washings reflect the general status of the urothelium, and because sampling of bladder washings can be performed as an outpatient procedure, patients can be monitored more carefully. To determine the actual value of bladder washing specimens in assessing the p53 status of histologic specimens, we used the technique of polymerase chain reaction-single-strand conformation polymorphism to analyze bladder washings and the synchronous tumors of 15 patients for the presence of p53 mutations. A significant correlation (2-tailed Fisher's exact test) between the p53 status of bladder washings and histologic specimens was observed if the 2 were compared among the specimens of a single patient. Overall, in 2 patients the mutation present in the tumors was not detected in the bladder washings, and in 1 patient the mutation in the bladder washing was not detected in the histologic specimens. These conflicting results obtained with bladder washings and histologic specimens could be explained mainly by the architecture of the tumors. The observed specificity of 86% and sensitivity of 75% emphasizes that although the correlation between the 2 methods is good, in a number of cases they are complementary to each other. The analysis of p53 mutations in at least 2 bladder washings gives insight into the p53 status of the synchronous tumors.
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PMID:Comparative analysis of p53 mutations in bladder washings and histologic specimens. 980 51

The diagnosis and follow-up of patients with bladder cancer rely on invasive procedures (cystoscopy with biopsy). Polymerase chain reaction (PCR)-based technologies may allow the sensitive detection of cancer-related genetic mutations in exfoliated tumour material, potentially allowing the development of less invasive techniques. This pilot study investigated the feasibility of detecting mutations in exons 5-8 of the p53 gene using single-stranded conformational polymorphism (SSCP) analysis in bladder-washing specimens from patients with bladder cancer. Bladder-washing samples (31) were collected from patients (27) with bladder cancer. An abnormal additional SSCP band was detected in five samples from five different patients suggesting the presence of a p53 mutation. In all five cases the same abnormal SSCP pattern was demonstrated in samples of the corresponding bladder tumour. In one case bladder washings were available from the same patient on two separate occasions with one washing demonstrating a mutation and the other not. In two further cases a mutation was demonstrated in the bladder tumour but not in the corresponding washing. It is concluded that it is possible to detect and characterize p53 mutations in bladder-washing samples from patients with bladder cancer. Improved sensitivity in detecting mutations in a sample containing a mixture of normal and malignant cells may lead to the clinical applicability of molecular methods of disease monitoring.
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PMID:p53 mutations as a marker of malignancy in bladder washing samples from patients with bladder cancer. 1063 80

The aim of this study was to determine whether p53 is helpful in making the decision to undergo cystectomy in T1, G3 transitional cell carcinoma (TCC) of the bladder, by prospectively comparing the p53 status of bladder biopsies with the histology and p53 status of the corresponding cystectomy specimens. From January 1996 to August 1997, 38 consecutive patients with T1G3 TCC at 6 different centres were enrolled into the study. Bladder biopsies and cystectomy specimens were examined with three different antibodies against p53. The p53 status of each bladder biopsy was compared with p53 status, tumour stage and grade of the cystectomy specimen. An independent evaluation of the histology and immunohistochemistry was carried out by two pathologists. 15 of 38 patients (39%) were found to have a higher tumour stage in the cystectomy specimen compared with the staging by transurethral resection of the bladder tumour (TUR-B). 3 patients did not show residual tumour in the cystectomy specimen. No differences in p53 positivity were noted between the different antibodies. 14 of 31 evaluable tumours (45%) were p53 positive at the time of the TUR-B. p53 staining of the TUR-B specimen did not correctly predict the residual tumour in the cystectomy specimen. We, therefore, concluded that compared with standard histopathology, the p53 status of the TUR-B specimen does not provide additional relevant information with regard to local tumour staging and, thus, is not helpful in making the decision for or against a cystectomy.
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PMID:p53 immunoreactivity in biopsy specimens of T1G3 transitional cell carcinoma of the bladder--a helpful parameter in guiding the decision for or against cystectomy? 1073 25

We have previously shown that bladder urothelium of people living in the cesium-137 ((137)Cs)-contaminated areas of Ukraine demonstrates accumulation of stable p53 and p53 mutational inactivation, preferentially through G:C to A:T transition mutations at CpG dinucleotides, with a codon 245 hot spot. In the present study, we analyzed immuno-histochemically the relationship between oxidative stress markers and over-expression of p53 and H-ras in urinary bladder urothelium from 42 men with benign prostatic hyperplasia. Bladder mapping biopsies were obtained from 15 patients from a highly radiocontaminated area (group I), 14 patients from the less contaminated city of Kiev (group II) and 13 patients as a control group from "clean" (without radiocontamination) areas of Ukraine (group III). Irradiation cystitis with multiple foci of severe dysplasia and carcinoma in situ were observed in 15 of 15 (100%, group I) and 9 of 14 (64%, group II) cases, with 4 small transitional-cell carcinomas incidentally detected in groups I and II. Markedly elevated levels of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2) and 8-hydroxy-2;-deoxyguanosine (8-OHdG) were noted in these bladder urothelial lesions from groups I and II, accompanied by strong over-expression of p53 and less H-ras expression. These findings support the hypothesis that iNOS, COX-2 and 8-OHdG in bladder urothelium are induced by long-term exposure to low-dose radiation with a close relationship to p53 over-expression that could predispose to bladder carcinogenesis.
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PMID:Increased oxidative stress with gene alteration in urinary bladder urothelium after the Chernobyl accident. 1084 92

Bladder tumors as the most common urologic malignancy present mostly as superficial transitional cell carcinoma. Many patients with superficial bladder cancer have a good prognosis, however, may develop recurrences or progress to muscle invasive or metastatic disease. It is therefore important to find new markers associated with the biological behaviour of an individual tumor for identifying patients at risk for disease progression. Previous reports on the prognostic significance of p53 alterations in bladder tumors revealed conflicting results. The aim of our study was to evaluate p53 mutation analysis as an effective concept for the characterization of subsets of superficial bladder tumors differing in biological aggressiveness. Screening 66 amplified DNA from micro-dissected tumor cells by direct genomic sequencing p53 alterations were detected in 12%. We found no association between p53 status and tumor stage but a tendency to a higher mutation rate in more malignant tumors (G2 and G3) compared to G1 tumors and a higher recurrence rate in patients with a p53 mutation in the primary tumor after 24 months follow-up. We conclude a general low incidence of p53 mutations in superficial bladder cancer. Detectable p53 damage might be related to a more aggressive phenotype and a higher recurrence risk. Our results are discussed in the context of other studies reviewed from 1995-2000.
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PMID:Prognostic significance of mutations in the p53 gene in superficial bladder cancer. 1094 16

Bladder cancers are classified as: transitional cell carcinoma (TCC), the most frequent in Europe/USA, squamous cell carcinoma (SCC), more frequent in the Middle East and in Africa, adenocarcinoma and small cell carcinoma, rare. TCC exhibit pseudo diploid karyotypes with only a few anomalies in early stages, evolving towards pseudo-tetraploides complexes karyotypes. Partial or complete monosomy 9 (-9) is an early event, found in half cases. Deletion (11p) or -11 is found in 20-50% of cases, more often in high grade and invasive tumours. Del(13q) is found in 25% of cases and correlated with high grade/stage; tumours with Rb alterations are invasives. Del(17p) is a late event, found in 40% of cases; P53 alterations are correlated with grade and stage, tumour progression, and a worse prognosis. Del(1p), i(5q), +7, and many other rearrangements - more often deletions than duplications - are frequently found. These losses of heterozygocity point to a multistep complex process involving tumor suppressor genes. In SCC, monosomy 9 is also an early event, even more frequent than in TCC; homozygous deletion of P16 is frequent. Trisomy 7 seems to be more frequent than in TCC. Chromosome 17 is often implicated, especially in high grades/stages; the profile of mutations of P53 is different from what is found in TCC. Allelic losses of 3p, 8p, 9p, 9q, 17p are frequent. The karyotype is more complex in advanced grades/stages, as in TCC.
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PMID:[From cytogenetics to cytogenomics of bladder cancers]. 1188 56

This work analyzes the effectiveness of wortmannin in boosting the lethality induced by different doses of X-rays, using the colorimetric assay of MTT. Bladder tumoral cell lines differing in radiosensitivity and p53 status were used. Since wortmannin is able to inhibit DNA-dependent protein kinase (DNA-PK) and rejoining of double-strand breaks (DSBs), we have analyzed the constitutive contents and expression after irradiation of the catalytic subunit of DNA-PK (DNA-PKcs) in our cell lines with the aim of explaining the differential effect of wortmannin as radiosensitizer. Considering that DNA-PK is the main protein complex involved in DNA DSB repair, the ability to remove DSBs after irradiation (with or without wortmannin) was evaluated in the different cell lines by the use of pulse-field gel electrophoresis. Our results indicate a higher radiosensitization in the radio-resistant cell line that shows both high constitutive contents of DNA-PKcs and a high rate of DNA repair by the fast component. In contrast, no radiosensitizer effect of wortmannin was observed in the radiosensitive cell line, previously characterized as defective in DSB repair by a low repair fidelity, and - as our results show - with low constitutive contents and later post-irradiation expression of DNA-PKcs. No clear effect related to p53 status of the cell line was observed. These results suggest that high constitutive contents of DNA-PKcs are indicative of radio-resistant phenotypes, and analysis of the expression of this protein could be helpful in the optimal establishment of wortmannin as radiosensitizer in bladder tumoral cell lines.
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PMID:Radiosensitizer effect of wortmannin in radioresistant bladder tumoral cell lines. 1465 54

Bladder urothelial carcinoma is typically a disease of older individuals and rarely occurs below the age of 40 years. There is debate and uncertainty in the literature regarding the clinicopathologic characteristics of bladder urothelial neoplasms in younger patients compared with older patients, although no consistent age criteria have been used to define "younger" age group categories. Use of the World Health Organization 2004/International Society of Urological Pathology 1998 grading nomenclature and recent molecular studies highlight certain unique features of bladder urothelial neoplasms in young patients, particularly in patients below 20 years of age. In this meta-analysis and review, the clinical, pathologic, and molecular features and risk factors of bladder urothelial neoplasms in patients 40 years or less are presented and analyzed according to decades of presentation. Similar to older patients, bladder urothelial neoplasms in patients 40 years or younger occur more common in male patients, present mainly with gross painless hematuria, and are more commonly located at bladder trigone/ureteral orifices, but in contrast have a greater chance for unifocality. Delay in diagnosis of bladder urothelial neoplasms seems not to be uncommon in younger patients probably because of its relative rarity and the predominance of benign causes of hematuria in this age group causing hesitancy for an aggressive work-up. Most tumors in patients younger than 40 years were low grade. The incidence of low-grade tumors was the lowest in the first 2 decades of life, with incremental increase of the percentage of high-grade tumors with increasing age decades. Classification according to the World Health Organization 2004/International Society of Urological Pathology grading system identified papillary urothelial neoplasms of low malignant potential to be relatively frequent among bladder tumors of young patients particularly in the teenage years. Similar to grade, there was marked predominance of low stage tumors in the first 2 decades of life with gradual inclusion of few higher stage and metastatic tumors in the 2 older decades. Bladder urothelial neoplasms occurring in patients <20 years of age lack or have a much lower incidence of aberrations in chromosome 9, FGFR3, p53, and microsatellite instability and have fewer epigenetic alterations. Tumor recurrence and deaths were infrequent in the first 2 decades and increased gradually in each successive decade, likely influenced by the increased proportion of higher grade and higher stage tumors. Our review of the literature shows that urothelial neoplasms of the bladder occurring in young patients exhibit unique pathologic and molecular features that translate to its more indolent behavior; this distinction is most pronounced in patients <20 years. Our overall inferences have potential implications for choosing appropriate noninvasive diagnostic and surveillance modalities, whenever feasible, and for selecting suitable treatment strategies that factor in quality of life issues vital to younger patients.
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PMID:Urothelial neoplasms of the urinary bladder occurring in young adult and pediatric patients: a comprehensive review of literature with implications for patient management. 2116 41


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