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)

Hyperplastic lesions of the oropharyngeal mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas (SCC) and provide an excellent model for multistage carcinogenesis. The development of carcinomas is assumed to be the result of the interaction of genetic factors, locally applied carcinogens and immunological unresponsiveness. Recently a novel gene termed mdm2 has been isolated that is found to be involved in transcriptional regulation and can inhibit p53 function by forming a complex with p53. In this study the immunohistochemical detection of the MDM2 protein in 186 paraffin embedded tissue sections of normal mucosa, premalignant, malignant and metastatic lesions of the oropharyngeal mucosa is reported for the first time. p53 protein expression was also investigated in the same tissue samples. The increase in the number of p53 and MDM2 positive biopsies was correlated with the dysplasia grade and the loss of differentiation in the premalignant and malignant lesions. In late stages of the disease the number of biopsies that expressed both p53 and MDM2 increased. Inactivation of p53 function in head and neck carcinogenesis may also be due to MDM2 binding. Detection of MDM2 protein expression by immunohistochemistry may be an important diagnostic tool in the future.
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PMID:Detection of p53 and MDM2 protein expression in head and neck carcinogenesis. 765 34

Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas (SCC) and provide an excellent model for multistage carcinogenesis. The development of carcinomas is assumed to be the result of interaction of genetic factors, locally applied carcinogens and immunological unresponsiveness. The purpose of this study was, therefore, to determine the role of alterations of the tumour suppressor gene p53, and the proliferation status of the lesions determined by PCNA expression. We investigated p53 and PCNA expression in 265 tissue sections of normal mucosa, premalignant, malignant and metastatic lesions of the oral mucosa by immunohistology. Quantitative analysis showed a gradual increase in PCNA expression from normal mucosa to moderately differentiated SCC. p53 expression was detectable in benign premalignant lesions. The increase in the number of p53-positive biopsies was correlated with the dysplasia and loss of differentiation in the premalignant and malignant lesions.
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PMID:p53 and PCNA expression in carcinogenesis of the oropharyngeal mucosa. 874 74

Hyperplastic lesions of the oral mucosa such as leukoplakia and oral lichen planus can eventually develop into squamous cell carcinomas. In the clinical treatment of these lesions it would be very important to be able to predict the biological behaviour of an individual lesion. In 64 hyperplastic lesions and 85 squamous cell carcinomas of the oral mucosa, the expression of the mutant tumor suppressor gene p53 was investigated. A positive correlation was seen between the expression of the mutant tumor suppressor gene p53 and the grade of dysplasia of the lesions.
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PMID:p53 expression in the carcinogenesis in the oral mucosa. 789 Aug 3

Sixty-two skin samples from patients with a variety of benign disorders (20 cases of psoriasis, 14 cases of chronic dermatitis, 11 seborrhoeic keratoses, 11 cases of lichen planus), and seven normal skin samples, were stained immunohistochemically with a polyclonal antibody (CM-1) to p53, and a monoclonal antibody to Ki67, using the avidin-biotin complex method. p53-positive keratinocytes could be found in most of these lesions. The percentage of p53-positive cells was, however, far lower than usually seen in p53-positive malignant tumours. No p53 reactivity was observed in the normal skin samples. Variable Ki67 reactivity was observed in all skin samples. Overall, the number of Ki67-positive cells was higher in skin samples in which the proportion of p53-positive cells was high (> 0.5% of total epidermal cell population) (P = 0.004). This also applied separately to psoriatic and non-psoriatic lesions (P = 0.028 and P = 0.033, respectively). In cases with > 10% of Ki67-positive cells, there were significantly more mitoses (P < 0.001). This association applied to both psoriasis and the other lesions studied (P = 0.024 and P < 0.001, respectively). The results show that immunohistochemically detectable accumulation of p53 is a frequent finding in non-neoplastic skin lesions. As p53 positivity was associated with the proliferation marker Ki67, the accumulation of p53 is possibly a response to an increased proliferation rate of the keratinocytes in these skin diseases, or alternatively it may be associated with apoptosis.
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PMID:Aberrant accumulation of p53 associates with Ki67 and mitotic count in benign skin lesions. 794 2

Hypothesizing that loss of basal cells in oral lichen planus is due to apoptosis, we evaluated LP specimens for apoptosis-regulating proteins [positive regulators Bcl-xS, Bax, Fas/Fas-ligand, p53, and negative regulators (anti-apoptotic) Bcl-2, Bcl-xL and compared results with reactions in normal mucosa and chronically inflamed gingiva. Also, sections were evaluated with an in situ TUNEL assay that identifies apoptotic DNA fragments. Basal keratinocytes in normal buccal mucosa, nonspecific gingivitis, and LP were negative for Bcl-2 protein, but melanocytes and lymphoid cells were positive. Keratinocyte staining for Bcl-x was negative to weak in normal buccal mucosa and gingivitis, and moderate in LP. Keratinocytes (especially upper prickle cells) in all tissues stained similarly for Bax at weak to moderate levels. Also, no differences in Fas and Fas-ligand staining were evident. Prominent p53-positive staining was seen in all LP biopsies (10-100% of basal keratinocytes) but not in normal buccal mucosa and gingivitis. Few basal keratinocytes in 5/10 LP cases exhibited a positive in situ signal for DNA fragment-associated apoptosis. That the Bcl-2 family of proteins and Fas/Fas-ligand were detected in normal and diseased tissues, and were occasionally expressed differently in oral LP, supports the notion that apoptosis is a potential mechanism of keratinocyte loss, especially in LP. The pattern of p53 staining in oral LP suggests over-expression of wild-type protein; a phenomenon that would arrest the cell cycle to allow repair of damaged DNA, or trigger apoptosis. While immunohistochemical evidence for apoptosis-associated basal keratinocyte death in LP was slight, it appeared that it may be p53 protein, and possibly Bcl-x associated.
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PMID:Apoptosis-associated markers in oral lichen planus. 989 Apr 58

The immunohistochemical detection of epithelial p53 protein expression in oral lichen planus (OLP) biopsies was supplemented with molecular analysis for mutations of the p53 gene using the polymerase chain reaction - single stranded conformational polymorphism (PCR-SSCP) technique. p53 protein expression, in the basal epithelial cell layer, as detected by the DO7 and 1801 antibodies, was significantly more frequent in OLP compared with other oral keratoses and normal mucosa, as was the growth fraction. The 10 OLP biopsies that had the most frequent p53 staining (plus a case of OLP found in continuity with a SCC) were screened by the PCR-SSCP technique, but no mutations were detected in the p53 gene (exons 5 9). The p53 overexpression in the OLP samples may be a physiological response to the hyper-proliferative state, as revealed by the growth fraction determination. This may usefully serve to protect against mutagenesis, and so be a factor in the low incidence of carcinoma associated with OLP.
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PMID:Epithelial p53 gene expression and mutational analysis, combined with growth fraction assessment, in oral lichen planus. 972 69

In an effort to identify genetic changes that may be the early hallmarks of epithelial cell overproliferation, we searched for p53 and nm23-H1 allelic deletions in oral benign epithelial lesions. In the study group were 25 benign epithelial lesions (lichen planus--17; leukoplakia--8; recurrent aphthous ulcers--2; one specimen diagnosed as benign migratory glossitis). Among 21 samples analysed for exon 4 (p53 gene) LOH, only 6 were informative, with no loss of either allele. OF 23 samples tested for LOH at intron 6 of p53 gene, 8 were informative, again with no presence of LOH. For nm23-H1 gene, the analysis was performed on a total of 24 cases. Of them, 16 were informative, however, none exhibited LOH at this locus. In conclusion, whereas the presence of gross gene alterations (LOH) would have been definitive evidence for the involvement of p53 and/or nm23 in the hyperproliferation process, the absence of LOH does not exclude the presence of either smaller mutations, altered regulation of normal gene, or dysfunction at the level of wild type protein. Alternatively, p53 and nm23-H1 may have no relation to oral lesion formation, and cannot presently be considered as an early step in benign, tissue transformation.
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PMID:The p53 and nm23-H1 genes are not deleted in oral benign epithelial lesions. 985 35

Although the pathogenesis of leukoplakia has been unclear, carcinogenic transformation is postulated to result from alterations of apoptotic signal transduction proteins in epithelial cells. The pathogenesis of oral lichen planus (OLP) has also been unclear, but apoptotic changes of the epithelial cells in OLP have been reported. In the present study, we used a histochemical approach to describe human keratinocyte-expression of several apoptotic signaling proteins in leukoplakia, in OLP, and in normal oral mucosa as a control. Mucosal biopsies from patients with leukoplakia (n=13), OLP (n=10), and normal oral mucosa (n=9) were frozen, sectioned and immunostained with monoclonal antibodies to wild-type (wt) tumor suppressive protein p53, cyclin-dependent kinase inhibitor p21WAF1/CIP1 and the oncoproteins MDM2, and Bcl-2. Apoptosis was assessed in all cases by the TUNEL method. MDM2 and Bcl-2 expression in keratinocytes were quantitatively greater in leukoplakia than in OLP. Wt-p53 and p21WAF1/CIP1 expression was quantitatively greater in keratinocytes in OLP than in leukoplakia. Keratinocyte maturation appeared histologically normal in OLP, even though wt-p53 and p21WAF1/CIP1 were expressed in these cells. Altered keratinocyte maturation was seen in leukoplakia lesions expressing MDM2 and Bcl-2. No significant difference for the number of apoptotic epithelial cells was observed between leukoplakia and OLP, in spite of the divergent outcomes of the apoptotic signaling proteins.
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PMID:Expression of apoptotic signaling proteins in leukoplakia and oral lichen planus: quantitative and topographical studies. 1097 47

Transformation in squamous cell carcinoma (SCC) may occur in a small percentage of patients affected by oral lichen planus (OLP), but the pathogenesis remains to be elucidated. Overexpression of p53 protein was investigated immunohistochemically in 28 cases of OLP, followed up by sequential biopsies for up to 96 months. In 15 cases (Group 1), no dysplastic changes or neoplastic transformation occurred during the follow-up period; in 7 cases, OLP and SCC were synchronously observed (Group 2), whereas in another 6 cases (Group 3) SCC developed several months or years after diagnosis of OLP. The percentage of p53-positive epithelial cells at first diagnosis was significantly higher in the cases of Groups 2 and 3 than in those of Group 1. In contrast, evaluation of growth fraction by MIB-1 monoclonal antibody did not show any statistical differences among the three groups. Although no conclusions can be drawn about the molecular pathway leading to neoplastic transformation of OLP, or about the role of p53, the results indicate that immunohistochemical evaluation of p53 expression may be a practical tool to select cases of OLP with a high risk of neoplastic transformation.
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PMID:Sequential immunohistochemical p53 expression in biopsies of oral lichen planus undergoing malignant evolution. 1127 27

Oral squamous cell carcinoma (OSCC) is a world-wide health problem. In addition to external exposure (smoking and alcohol), certain oral lesions may increase the risk of oral cancer (e.g. leukoplakia, erythroplakia, and oral lichen planus). TP53 has been implicated in OSCC, but there are limited studies of mutations in premalignant oral lesions. In this study, 55 samples from OSCC, 47 from hyperkeratotic (HK) oral mucosa, clinically diagnosed as white patches, 48 samples from oral lichen planus (OLP), and 12 biopsies from normal oral mucosa were studied immunohistochemically for expression of TP53 protein. From all the carcinoma samples and selected non-malignant samples showing moderate or strong TP53 protein expression, malignant cells or TP53-positive nuclei were microdissected and screened for mutations in exons 5-8 by constant denaturation gel electrophoresis. Moderate to strong TP53 protein staining was seen in 56% of OSCC, 32% of OLP but only in 13% of HK. All OLP samples showed a characteristic pattern of positive nuclei confined to the basal layer, whereas TP53 staining was seen in suprabasal nuclei in HK. Mutation rate was 11 out of 52 for OSCC, three out of 20 tested for HK and, remarkably, nine out 27 tested for OLP. There was no correlation between TP53 protein staining and TP53 mutations. No associations were found with anatomical sites or disease progression. The unexpectedly high mutation rate of OLP might explain the premalignant potential of this lesion.
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PMID:Oral lichen planus has a high rate of TP53 mutations. A study of oral mucosa in icelanD. 1212 Jul 3


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