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)

The combined efforts of a number of investigators have led to the identification of the VHL gene, which appears to function as a tumor suppressor gene and is implicated in both sporadic and familial forms of RCC. These findings should increase our understanding of the molecular biology of this malignancy; however, there is much work to be done. Identification of the mechanism of inactivation of the VHL gene, as well as the structure and function of the VHL gene product, ultimately may provide clinicians with greater understanding of this malignancy as well as with methods for earlier diagnosis. The role of other tumor suppressor genes, such as p53, is incompletely understood. It is hoped that the techniques that have been applied to the study of RCC also will result in advances in our knowledge of other urologic malignancies.
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PMID:Renal cell carcinoma. Molecular genetics and clinical implications. 779 82

In this study both the incidence and pattern of p53 over-expression in various histological subtypes of a series of 36 cases of renal cell Grawitz carcinoma, partially studied in a previous paper, were analyzed. This series consisted of these histologic subtypes: clear cell non papillary (18 cases), clear cell papillary (2 cases), granular cell (5 cases), mixed (clear and granular cell) (9 cases) and spindle cell (2 cases). At present, our aim was, firstly, to see which were the best technical conditions for detection of p53 in the available paraffin-embedded tumor specimens, using several antibodies, specific for various epitopes; secondly, to investigate if some relation might exist between this expression and the histological features of these tumors. Twenty-five per cent (9/36 cases) resulted p53 immunoreactive, the highest percentage being represented in the papillary clear and granular cell carcinomas; low expression was detected in 11 cases (30%) and no reactivity in 16 cases (44%). Neither technical or dilution modifications proved to transform these latter results; however, detection was maximal using the CM-1 polyclonal rabbit antiserum. Thus, in RCC, expression of p53, analyzed in the light of the cytogenetic characterization through a literature review, resulted at low frequency. This finding means that mutation of the p53 gene are not frequent in the neoplastic transformation in RCC. Nevertheless, in spite of the small number of cases and of the short follow-up period of this study, detection of p53 positivity in tumors with either high grade and stage or high proliferative activity could suggest that p53 mutations lead to tumors of a more aggressive type.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:p53 expression in human renal cell carcinoma: an immunohistochemical study and a literature outline of the cytogenetic characterization. 780 90

Genomic DNA from 53 primary human renal cell tumors was screened for the presence of mutations in the tumor suppressor gene p53, using the polymerase chain reaction and single-strand conformation polymorphism analysis, followed by direct sequencing of DNA. Five cases showed mobility shifts. Sequencing of these samples revealed two cases of nonsense mutations (codons 182, 192), one case of a missense mutation (codon 285), and two cases of silent mutations at codon 213. The frequency of mutations altering the p53 (3/53 = 6%) was low when compared with the reported frequencies (15% to 65%) of allelic loss of 17p (location of p53) in renal cell cancers, suggesting the possible existence of another tumor suppressor gene in the region of the p53 gene, which when mutated is associated with these cancers. All three tumors with p53 mutations were cases with poor prognosis, i.e., highest pathological grade and/or advanced Robson stage. The human equivalent of the murine double-minute-2 was not amplified in the renal cell tumors. In summary, alterations of p53 may be associated with the development of renal cell carcinoma of higher grade and/or stage.
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PMID:p53 mutations and MDM-2 amplification in renal cell cancers. 782 11

Renal cell carcinomas sometimes show sarcomatoid transformation, thus comprising both sarcomatous and carcinomatous components. Such sarcomatoid renal cell carcinomas are highly malignant with pronounced proliferative activity. The present investigation was conducted to assess the mutational status of the p53 and H-ras genes independently in carcinomatous and sarcomatous portions of individual tumors, applying PCR, subcloning, and sequencing to 14 cases. Sarcomatoid portions showed an extremely high mutation rate for the 53 gene (11 of 14, 78.6%) with two mutational hot spots at codons 278 (8 of 14, 57.1%) and 244 (6 of 14, 42.9%). Five cases showed double mutations, four cases had mutations at codons 278 and 244, and one case had mutations at codons 278 and 248. In contrast, the carcinomatous portions demonstrated a low mutation rate for the p53 gene (2 of 14, 14.3%) and no double mutations were detected. Ten cases showed genetic heterogeneity in the p53 gene between the two tumor components. Furthermore, p53 overexpression was immunohistochemically observed only in those components with p53 mutations, mainly in the sarcomatoid portions. No H-ras mutations were observed. The findings strongly suggest that p53 mutations leading to overexpression of p53 protein are closely associated with sarcomatoid transformation in renal cell carcinomas.
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PMID:Mutations of the p53 gene and p53 protein overexpression are associated with sarcomatoid transformation in renal cell carcinomas. 783 36

In this study we investigated 56 renal cell carcinomas immunohistochemically for the expression of proliferating cell nuclear antigen (PCNA) and tumour suppressor protein p53. We also analyzed for the presence of human papilloma virus (HPV) DNA subtypes 6, 11, 16, 18, 31 and 33 by in situ hybridization. In carcinomas which showed more than 10% of PCNA positive nuclei there were significantly more cases with invasion (P = 0.032) or metastatic disease (P = 0.047). Nine out of 22 grade III-IV tumours (40.9%) but only six out of 30 grade I-II tumours (20%) showed more than 10% of PCNA positive cells (P = 0.097). Patients with 10% or more PCNA positive cells in kidney tumours had more advanced disease at the time of diagnosis than those showing less PCNA positive cells (P = 0.05). Six p53 positive cases were found among 56 tumours (11%), but only one case had more than 10% positive cell nuclei. The presence of HPV DNA was found in 29 out of 56 cases (52%). Multiple subtypes were found in 19 cases (34%). The most commonly occurring subtypes were 18 and 33. There was no association between PCNA, p53 and the presence of HPV DNA subtypes. Because of the association of PCNA with invasion and metastatic disease, it would be worth while to study PCNA further as a possible marker for aggressiveness of renal carcinomas. Both this study and those concentrated on mutational analysis suggest that p53 is generally not important for the development of renal cell carcinoma. On the other hand, the presence of HPV DNA in these tumours implicates HPV viral infection in the aetiology of renal cancer.
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PMID:Proliferating cell nuclear antigen but not p53 or human papillomavirus DNA correlates with advanced clinical stage in renal cell carcinoma. 783 39

With DNA polymerase chain reaction-single strand conformation polymorphism assay followed by direct DNA sequencing, p53 gene mutation was examined in bladder transitional epithelial cell carcinoma, renal cell carcinoma and testicular seminoma. p53 gene mutation was found in 7 cases (35%) of bladder carcinoma and 4 cases (23.5%) of testicular seminoma. Inactivation of Rb gene and activation of ras and c-erbB-2 were also studied. The results suggest that development of urologic neoplasms is closely associated with p53 gene mutation and involves loss of expression of Rb and aberrant expression of ras and c-erbB-2.
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PMID:[Mechanism of p53 gene mutation in the development of urologic cancer]. 786 97

Mutant forms of p53 gene are found in numerous human malignancies. Studies of the p53 mRNA showed different levels of expression in many tumours. But the relationship between the p53 gene and the renal cell carcinoma is less elucidated than the other. In this report we examined p53 gene at mRNA level by Northern blot on the tissues from 21 patients with renal cell carcinoma. Abnormalities of the p53 were found in 12(57%) tumors, in which seven had elevated level of p53 mRNA, and five lacked p53 mRNA. p53 gene alteration occurred in a high percentage in high-grade and advanced tumors. These results suggest that inactivation of p53 gene is common in renal cell carcinoma and may be involved in the progression of this malignancy.
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PMID:[Abnormalities of anti-oncogene p53 in renal cell carcinoma]. 788 75

Expressions of proliferating cell nuclear antigen (PC10), p53 protein (CMI) and c-erbB-2 (NCL-1) were immunohistochemically analysed in 123 renal adenocarcinomas with known follow-up data. c-erbB-2 protein was weakly and focally expressed in 10% of the tumours, and the expression was not related to clinical or histological variables or survival. p53 protein was expressed in 33% of the tumours. Expression of p53 protein was independent of stage, grade and prognosis, while expressions of c-erbB-2 and p53 were weakly interrelated. Proliferating cell nuclear antigen was expressed in all tumours, and the fraction of PC10-positive nuclei was significantly related to grade, stage and prognosis. Multivariate analysis of clinical, histological and immunohistochemical prognostic factors indicated that the extent of the tumour, its histological differentiation and proliferation rate of the cancer cells are the most important prognostic factors. Recurrence-free survival was related to the fraction of PC10-positive nuclei, histological differentiation, sex and expression of p53 protein. Over-expression of p53 protein was related to a long recurrence-free survival. Our results show that PC10 immunolabelling can be used to determine the prognostic category in renal adenocarcinoma, whereas the expressions of p53 protein or c-erbB-2 are only weak prognostic indicators.
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PMID:Expression of proliferating cell nuclear antigen (PC10), p53 protein and c-erbB-2 in renal adenocarcinoma. 790 98

Thirty-six primary renal cell carcinoma samples and one metastatic lymph node DNA sample were examined for mutations of H-, K-, and N-ras and p53 genes, and genomic instability at (AC)n, (CA)n.(GT)n, and (TA)n.(GT)n repeats. No mutations were noted for H-, K-, and N-ras genes and only 2 of all the samples (5.6%) showed mutations at exon 8 of the p53 gene. Differences in unrelated microsatellites for tumor and normal DNA were detected in 9 (25.0%) of the cases examined. Somatic alterations in seven microsatellites, D3S1228, D3S643, D5S107, LPL5GT, D9S63, D17S261, and DCC, were found in 1 (2.8%), 3 (8.3%), 2 (5.7%), 5 (14.7%), 3 (8.3%), 3 (8.3%), and 3 (8.3%) cases, respectively. Five of 26 (19.2%) clear cell type and 4 of 10 (40.0%) non-clear cell type patients showed DNA instability. Two of 11 (18.2%) grade 1, 5 of 20 (25.0%) grade 2, and 2 of 5 (40.0%) grade 3 patients showed abnormal patterns. One of 2 (50.0%) stage pT1, 4 of 24 (16.7%) stage pT2, and 4 of 10 (40.0%) stage pT3 patients were shown to have microsatellite instability. In 4 of 9 alteration-positive cases (44.4%), mutations in multiple microsatellites were observed. Alterations in microsatellite instability may be more common in non-clear cell type, high-grade, and high-stage renal cell carcinoma patients.
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PMID:Genomic instability of microsatellite repeats and mutations of H-, K-, and N-ras, and p53 genes in renal cell carcinoma. 803 84

Restriction fragment length polymorphism (RFLP) analysis and the polymerase chain reaction of the single-strand conformation polymorphism (PCR-SSCP) method were conducted to assess the loss of heterozygosity of chromosome 17p and mutations of the p53 gene in 30 surgical specimens of human renal cell carcinoma. Six of 29 tumors (20.6%) showed loss of heterozygosity on chromosome 17p in RFLP analysis, and in none of 21 tumors could a mutation be found on exons 5 to 8 of the p53 gene in PCR-SSCP analysis. We conclude that the p53 gene mutation does not play a role in the development of the majority of cases of renal cell carcinoma and that there may be another tumor suppressor gene on 17p.
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PMID:Infrequent involvement of p53 mutations and loss of heterozygosity of 17p in the tumorigenesis of renal cell carcinoma. 810 6


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