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)

Evaluation of the clinical significance of p53 gene mutations requires molecular analysis of primary tumors from large series of patients with long follow-up periods. In this study, we describe a sensitive, rapid, nonisotopic and inexpensive procedure for the polymerase chain reaction (PCR)-single-stranded conformational polymorphism (SSCP) detection and subsequent sequencing of p53 mutations in formalin-fixed and paraffin-embedded tumor (PET) samples. To optimize this method, we used a panel of 34 mutations previously identified in this gene by isotopic PCR-SSCP analysis of frozen colorectal carcinomas. Identical SSCP band shifts were observed in PET sections from each of these frozen tumors, except for one case in which the tumor cell content was probably too low. All of the 34 mutations were detected by use of an optimized minigel SSCP/silver staining procedure. The total PCR-SSCP screening time with use of this protocol was less than 8 hours. An additional improvement was the use of multiplex SSCP to screen two p53 exons (5/7 and 6/8) simultaneously, thus effectively halving the amount of reagents and time required for mutation analysis. To identify the exact nucleotide alterations, mutant single-stranded DNA was excised from silver-stained SSCP gels, reamplified, and used as template in sequencing reactions. The PCR-SSCP procedure we describe can be performed in routine histopathology laboratories, requiring only a thermal cycler and minigel electrophoresis apparatus. Our results demonstrated the feasibility of conducting large retrospective analyses of p53 gene mutation status in archival tumor material. Studies of this kind should allow elucidation of the clinical role of p53 mutation in various human cancer types.
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PMID:A rapid and nonisotopic method for the screening and sequencing of p53 gene mutations in formalin-fixed, paraffin-embedded tumors. 907 34

p53 and the murine double minute 2 (MDM2) oncoprotein expression was evaluated in paraffin-embedded tissue from 61 patients with central nervous system gliomas (53 astrocytomas and eight oligodendrogliomas) and related to proliferation-associated markers [i.e. proliferating cell nuclear antigen (PCNA), Ki-67 and nuclear organizer regions (NORs)] and epidermal growth factor receptor (EGFR). We used the monoclonal antibodies PC-10, MIB-1, DO-1, 1B1O and EGFR 113 and the colloid silver nitrate (AgNOR) technique. MDM2 and p53 were co-expressed in 28% of cases. A p53-positive/MDM2-negative phenotype was observed in 15% and a p53-negative/MDM2-positive phenotype in 20% of cases. There was a positive correlation of p53 and MDM2 expression with grade and proliferation indices. Univariate analysis in the group of diffuse astrocytomas showed that older age, high histological grade, high PCNA labelling index (LI) and high AgNOR score were associated with reduced overall survival (P < 0.05). p53 LI, Ki-67 LI, AgNOR score, tumour location and grade influenced disease-free survival (P < 0.05), whereas the only parameters affecting post-relapse survival were histological grade and Ki-67 LI (P < 0.1). Multivariate analysis revealed that age, radiotherapy, PCNA LI and p53 LI were the independent predictors of overall survival. p53 LI, Ki-67 LI, MDM2 LI, EGFR LI, grade and type of therapy were independent predictors of disease-free survival, and grade was the only independent predictor of post-relapse survival. Our results indicate that p53 LI and MDM2 LI, EGFR expression as well as proliferation markers (PCNA and Ki-67) are useful indicators of overall and disease-free survival in diffuse astrocytoma patients.
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PMID:MDM2 and p53 expression in gliomas: a multivariate survival analysis including proliferation markers and epidermal growth factor receptor. 915 45

To investigate the relation between the clinicopathological findings, and the survival of patients with malignant tumours of the maxillary sinus, and the tumour's biological parameters, we examined the expression of p53 and bcl-2 and the number of silver-stainable nucleolar organizer regions (AgNORs) in 23 paraffin-embedded specimens from primary tumours. Fifteen of 23 (65 per cent) maxillary tumours expressed p53 and two of 23 (nine per cent) tumours expressed the bcl-2 gene product. The mean number of AgNORs per nucleus was 5.2 +/- 2.4. There was no relationship between the expression of p53 or bcl-2 and the patient's clinical course. In contrast, there was a statistically significant difference in the survival of patients with a high (> 6) number of AgNORs and patients with a low (< 6) number of AgNORs. These data suggest that the number of AgNORs may be useful in evaluating the prognosis of patients with malignant maxillary sinus tumours.
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PMID:p53 and bcl-2 expression and argyrophilic nucleolar organizer regions in patients with malignant maxillary sinus tumours. 929 29

Disease stage is the most important factor in determining prognosis and treatment of lung cancer. Staging of lung cancer is complicated by presentation of multiple pulmonary malignant lesions with a similar histology. It is a dilemma to decide if these lesions are synchronous primaries arising from different malignant clones or metastases from a single clone. Lung cancer is associated with multiple genetic abnormalities including mutations of K-ras and p53, which are believed to occur prior to onset of metastasis. To determine the clonal origin of multiple pulmonary malginant nodules, we analyzed point-mutations of K-ras and p53 by microdissection, polymerase chain reactions (PCR), nonradioisotopic single-strand conformation polymorphism (SSCP) analysis, and DNA sequencing. Each pulmonary lesion was microdissected from paraffin slides. Genomic DNA was amplified by two sequential PCRs followed by electrophoresis in a minigel and silver staining. Deoxyribonucleic acid sequencing was performed if necessary to confirm a mutation found upon SSCP analysis. Applying this molecular approach, we were able to differentiate the clonal origins of multiple malignant nodules of the lung as exemplified by the two cases presented.
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PMID:Clonal origin of multiple lung cancers: K-ras and p53 mutations determined by nonradioisotopic single-strand conformation polymorphism analysis. 936 Aug 38

In order to increase the sensitivity to immunostaining in formalinfixed, paraffin-embedded tissues, we developed an immunohistochemical method by microwave heating of tissue sections instead of trypsin digestion. The results of this study showed that there was no positive P53 protein reaction in normal and hyperplastic mucousa of human mouth, whereas 90% (27/30) of cases with dysplasia, 61% (30/49) of oral squamous cell carcinomas and 86% (13/15) of regional metastatic lymph nodes were positive. And all positive reactions were localized in nuclei. Comparison of these positive results of p53 gene mutation detected by silver staining method with the results by polymerase chain reaction-single strand conformation polymorphism analysis did not reveal matched results, especially during the precancerous period. The authors analysed the causes of difference not only by methodology, but also by cell groups which had different genetic changes in tissues of precancerous lesions.
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PMID:[The role of p53 gene during the development of human oral malignant lesions: a comparative study of p53 gene mutation with P53 protein positive immunostaining]. 938 53

It is widely accepted that the inactivation of P53 tumor suppressor gene is related to the tumorigenesis of many cancers. The study on P53 tumor suppressor gene has become a hotspot in molecular oncology. But until now, the reports on the research of the role of P53 gene in the tumorigenesis and prognosis of oral squamous cell carcinoma are scarce. So, two studies have been carried out. (1) A silver staining method of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis was established by detecting the mobility shifts of the DNA bands of the products of PCR of mutant P53 gene plasmid and the Sup F mutants which had been proved to have point mutation by DNA sequencing in shuttle vector plasmid pS 189 mutagenesised by N-methyl-N-nito-N-nitosoguanidine (MNNG). For the method is non-radiation with high sensitive, it has applicable value. (2) By silver staining PCR-SSCP system, tissues from normal oral mucoas membrane to metastatic oral squamous cell carcinoma (OSCC) were analyzed and the results showed that tissues from 53% oral precancerous lesions and 65% OSCC had abnormal SSCP bands and the abnormal frequency of metastatic cancers was higher than that of nonmetastatic ones. These suggest that P53 gene mutation plays some role on the process of initiation, development and metastasis of OSCC.
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PMID:[The role of P53 gene in the development of oral squamous cell carcinoma: study of P53 gene mutation by silver staining polymerase chain reaction-single strand conformation polymorphism]. 959 86

In order to diagnose lung cancer at gene level, bronchial biopsy specimens from lung cancer patients, who were diagnosed by pathologic method using biopsy specimens from the same site, were used for detection of p53 gene mutation by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP)-silver staining method. 15 of 25 (60%) specimens were found to be positive. In 10 small cell lung cancer specimens, 7 were positive; in 15 non-small lung cancer specimens, 8 were positive. These results coincided with those of other reports using surgical specimens and sequencing method. Clinical analysis showed no correlation between SSCP positivity and the patients' clinical data such as age, sex, smoking habit, stage of tumor at the time of diagnosis. It is concluded that a small piece of bronchial biopsy specimen could be used to detect p53 gene mutation instead of surgical specimens and this method might be used as an adjunct to cancer screening or for a gene diagnosis prior to gene therapy. In comparison with the routine radionuclide labelled method, silver staining method has the advantage of being simple, quick, economic, safe and convenient for clinical use.
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PMID:[Detection of p53 gene mutation in bronchial biopsy samples from lung cancer patients with polymerase chain reaction-single strand conformation polymorphism-silver staining method]. 959 39

Paraffin-embedded asbestos-related lung cancer tissue of ten cases was analyzed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) to study its genetic mutation of exon 5, 7 and 8 of anti-oncogene p53 by silver stain. Results showed that fragment of exon 7 or 8 of p53 gene in four cases was positive in silver-staining analysis of PCR-SSCP. Exon 7 or 8 fragments of p53 gene was detected positive for mutation in seven of these ten cases with autoradiographic analysis of PCR-SSCP. No exon 5 fragment was found positive for mutation in these ten cases with both methods. Agreement between results of silver staining and those of autoradiographic PCR-SSCP was 60%. Hence, autoradiographic method could be replaced by silver staining, a simpler and more sensitive one, in PCR-SSCP to study gene mutation of asbestosrelated lung cancer.
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PMID:[Detection of p53 gene mutation in paraffin-embedded asbestos-related lung cancer tissue]. 981 77

The aim of this study was to assess the relation between silver-strained nucleolar organizer regions (AgNOR), tumor stage, tumor grade and p53 expression with cathepsin B staining in transitional cell carcinoma of bladder. Tissue sections from 64 transitional cell carcinomas of the bladder were evaluated for the relation between AgNOR, tumor stage, tumor grade and p53 expression with cathepsin B staining in the neoplastic and stromal cells. Mean AgNOR values were significantly higher and the presence of p53 expression were different in cathepsin B positive and negative tumor and stromal cells. Although the number of cases is limited, this pilot study shows that cathepsin B staining may have a prognostic value in transitional cell carcinoma, but more studies are needed for a definite conclusion.
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PMID:Cathepsin B, p53 expression and AgNORs in transitional cell carcinoma. 1021 Jan 9

The human embryonic lung fibroblasts transformation was induced by chemical mutant Glycidyl Methacrylate (GMA) in vitro. Transformed clonies were isolated and then exon 5 and exon 8 of p53 gene were specifically amplified by polymerase chain reaction. Amplified fragments were detected by using silver stained single strand conformation polymorphism analysis. The results showed that exon 8 altered in the transformed cells, indicating that p53 gene played an important role in the human embryonic lung fibroblasts transformation induced by GMA.
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PMID:[Mutation of p53 gene in the transformed fibroblasts detected by nonradioisotopic single strand conformation polymorphism analysis]. 1032 25


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