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)

Apoptosis or programmed cell death represents a mechanism by which cells possessing DNA damage can be deleted. The bcl-2 proto-oncogene is a known inhibitor of apoptosis that may allow the accumulation and propagation of cells containing genetic alterations. To determine if and when the bcl-2 gene is activated during colorectal tumorigenesis and its relationship to p53, we analyzed normal mucosa, hyperplastic and dysplastic epithelial polyps, and carcinomas for the expression of these markers using immunohistochemistry. Whereas bcl-2 staining was restricted to basal epithelial cells in normal and hyperplastic mucosa, bcl-2 expression was detected in parabasal and superficial regions in dysplastic polyps and carcinomas. An inverse correlation was found between bcl-2 and p53 expression in adenomas, suggesting that these markers may regulate a common cell death pathway. Furthermore, carcinomas with a high percentage of bcl-2-positive cells were significantly more likely to have low rates of spontaneous apoptosis, as determined histologically, than those cancers with low or absent bcl-2 expression. Abnormal activation of the bcl-2 gene appears to be an early event in colorectal tumorigenesis that can inhibit apoptosis in vivo and may facilitate tumor progression.
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PMID:bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. 781 51

To determine the incidence of p53 mutations in pre-malignant lesions of the oral cavity from individuals without prior history of tobacco use, we have analyzed the conserved regions of the p53 gene (exons 5-9) in archival oral cavity lesion specimens obtained from patients with varied tobacco use histories, by polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and DNA sequencing analysis. Twenty-six lesions were analyzed from 14 patients, with multiple lesions obtained from 8 patients. Six of these patients used tobacco, (3 being cigarette smokers, 1 ex-cigarette smoker, 1 moderate cigar smoker and 1 snuff chewer). The remaining 8 patients had no prior history of tobacco use. Thirteen of the pre-malignant lesions exhibited severe dysplasia, 9 exhibited moderate dysplasia and 4 exhibited mild dysplasia. Four of the 26 lesions exhibited p53 mutations, each being from a tobacco user. None of the 13 lesions from never-tobacco users exhibited p53 mutations. There was a significantly higher p53 mutation incidence in pre-malignant lesions from tobacco users (including ex-smokers) than in non-tobacco users as well as in cigarette smokers plus snuff chewers than in non-tobacco users. Two of the mutations were observed in lesions exhibiting severe dysplasia: 1 in a lesion exhibiting moderate dysplasia and 1 in a lesion exhibiting mild dysplasia. These data suggest that p53 mutation may be a very early event in oral cavity tumor progression and demonstrate that pre-malignant lesions obtained from non-tobacco users do not exhibit p53 mutations.
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PMID:A low incidence of p53 mutations in pre-malignant lesions of the oral cavity from non-tobacco users. 782 58

The wild-type p53 gene is thought to play a critical role in tumor suppression and has been shown to reverse the transformed phenotype of tumor cells in vitro. Mutational inactivation of this aspect of p53 activity occurs frequently in many human neoplasms, including astrocytomas, and is thought to represent a critical step in tumor progression. We have found previously that the presence of p53 immunoreactivity was significantly associated with malignant astrocytomas arising in younger patients, although occurring infrequently in tumors in older patients. Given that young age is the most consistent clinical factor predictive of longer survival in patients with astrocytomas, this suggested that p53 protein accumulation might be a molecular predictor of enhanced survival. To test this hypothesis, we retrospectively studied the association of p53 overexpression with survival in 149 patients with astrocytomas, using univariate and multivariate analysis to determine its value in predicting survival. Although our analysis reaffirmed the strong association between young age and increased survival, we were unable to demonstrate any difference in survival between patients with Grade III and IV tumors with p53 immunoreactivity compared with those without. Presumably, once a tumor has progressed to high grade, the relative importance of p53 status as a predictor of survival is low, probably because of the large number of accumulated genetic alterations associated with malignant tumors. In contrast, the presence of p53 overexpression in Grade II astrocytomas seemed from survival curves to indicate shorter survival compared with patients who had no p53 immunoreactivity. However, this variable did not quite reach statistical significance (P = 0.08) as an independent predictive variable in multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic implications of p53 overexpression in supratentorial astrocytic tumors. 783 30

In order to determine whether or not the p53 gene is involved in the malignant transformation of the head and neck carcinoma HNSCC, we have analyzed archival specimens from 527 primary head and neck lesions and 27 corresponding lymph node metastases. Nuclear p53 protein was present in 107 of 190 (56%) dysplasias, 61 of 102 (60%) carcinoma in situ (CIS), and 262 of 493 (53%) carcinomas. The p53 score did not increase significantly with progression of these lesions from dysplasia to CIS and to carcinoma. All 357 normal samples of head and neck tissues were negative. The majority of the 172 sets of premalignant and malignant lesions displayed concordant p53 staining patterns. The staining was incongruous in only six cases. The p53 staining results were congruent in all 27 pairs of primary and metastatic (lymph nodes) tumors. These data strongly suggest that p53 protein could be altered in a very early phase of the head and neck tumorigenesis and is maintained during tumor progression and metastatic spread. Mutations in p53 were examined in 11 cases that exhibited high levels of p53 protein as detected by immunohistochemistry using PAb 1801 MAb. Mutation analysis was performed by direct sequencing of the PCR amplification products of exons 5 through 8, which contain greater than 90% of p53 mutations found in tumors. Three of 11 HNSCC had mutations at codon 130 (C to A), 193 (A to T), 283 (G to C), respectively. No mutations were found in the other 8 samples within the regions examined. However, they may have mutations in unsequenced regions of p53 or may have wild type protein that accumulates for other reasons.
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PMID:Overexpression of p53 protein is common in premalignant head and neck lesions. 784 May 33

To investigate the molecular mechanism of gastric carcinogenesis, we examined simultaneously the frequency of microsatellite instability and the immunoreactivities to ras, erbB-2, and p53 in 42 gastric adenocarcinoma tissues. Microsatellite instability, measured by DNA replication error, was detected in 33.3% (14/42) of patients with gastric carcinoma while positive immunostaining was demonstrated in 3.1% (1/32) for ras, 40.5% (17/42) for erbB-2, and 28.6% (12/42) for p53. There was no statistical difference between the intestinal type and the diffuse type of carcinoma with respect to microsatellite instability, ras, or erbB-2 expression. The expression of p53 occurred more frequently in the intestinal type of carcinoma (41.7%, 10/24) than in the diffuse type of carcinoma (11.1%, 2/18; P < 0.01). There was no association between microsatellite instability and ras or p53 expression, while enhanced expression of erbB-2 occurred more frequently in carcinomas with microsatellite instability (64.3%, 9/14) than in those without microsatellite instability (28.6%, 8/28; P < 0.05). Such a strong association between microsatellite instability and erbB-2 oncogene may be responsible for the increase of other oncogenic mutations and tumor progression in gastric carcinogenesis.
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PMID:Occurrence of microsatellite instability in gastric carcinoma is associated with enhanced expression of erbB-2 oncoprotein. 788 46

In this study, we examined the expression of c-fos, c-myc, mutant c-Ha-ras and mutant p53 proteins in three normal human melanocyte cell lines and the following 12 melanoma cell lines: M5, Mewo, A375, Bro, Mel 2a, O-Mel II, IgR 39, SkMel-13, -19, -28 Mel-57 and NKI-4, using an immunohistochemical assay (APAAP). An effort was made to correlate oncogene expression with growth parameters, differentiation antigens (HMB-45, vla-2, k.1.2.58, HLA-DR, HLA-I), and pigmentation. All melanocyte cell lines were negative for the oncogenes examined, whereas six of the melanoma cell lines were found also positive (three for c-fos, two for c-myc, one for c-Ha-ras, and four for p53). Three melanoma cell lines expressed one oncogene and three the combination c-fos/p53. These three melanoma cell lines were positive for the "late" tumor progression marker A. 1.43 (vla-2 adhesion molecule) and negative for the differentiation marker k. 1. 2. 58. Positivity for A. 1. 43 combined with negative staining for k. 1. 2. 58 was found in six out of the 12 cell lines. The observed oncogene expression correlated neither with growth parameters nor melanin content. The present findings revealed a coexpression of mutant p53 and c-fos proteins being associated with a highly malignant phenotype in melanoma cell lines. Further studies are necessary to clarify the significance of the above findings.
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PMID:P53 mutation and c-fos overexpression are associated with detection of the antigen VLA-2 in human melanoma cell lines. 788 7

We analyzed the p53 expression immunohistochemically in 50 specimens of hepatocellular carcinoma (HCC) using two monoclonal antibodies (DO7 and PAb1801) and one polyclonal antibody (CM1), which recognize both wild and mutant type p53 proteins and can be used for paraffin-embedded sections. Fifteen of the 50 HCC specimens (30%) showed p53 expression localized at tumor nuclei, and this expression was significantly more frequent in HCCs with histologically lower differentiation. Except for serum titers of alpha-fetoprotein, the p53 expression had no statistically significant correlation with clinicopathological parameters, including hepatitis virus infection, tumor size, and background liver diseases. Conversely, the cell proliferative activities of tumor cells as assessed by mitotic index and immunostaining for MIB-1 were well correlated with the grade of histological differentiation. Moreover, MIB-1 immunostaining was shown to be useful in distinguishing well differentiated HCC from hepatocytes in chronic liver diseases. It also was shown that p53 expression was strongly associated with cell proliferative activity. Our results indicate that p53 expression takes place in the late stage of tumor progression and is related to the high malignant potential of HCCs.
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PMID:Immunohistochemical detection of aberrant p53 expression in hepatocellular carcinoma: correlation with cell proliferative activity indices, including mitotic index and MIB-1 immunostaining. 789 Feb 86

To study genetic alterations related to the development and/or progression of breast carcinoma, we examined amplification of the ERBB2, INT2, and MYC genes, as well as loss of heterozygosity (LOH) at loci on 11p, 16q, 17p (D17S5 and TP53), 17q (D17S74 and NME1), and 18q by restriction fragment length polymorphism analysis. The subjects were 26 patients with small breast carcinomas (< or = 2 cm) and 88 patients with larger breast carcinomas (2 to < 5 cm). All patients were free of distant metastasis. As tumor diameter increased, the frequency of oncogene amplification and LOH at all loci except D17S5 increased. However, there was no relationship between tumor diameter and amplification of specific oncogenes or allelic loss at specific loci. LOH at D17S5 was detected in 40% of small breast carcinomas (< or = 2 cm) and 43% of larger breast carcinomas (2 to < 5 cm). There was a significant correlation of LOH at D17S5 with INT2 amplification or with LOH on 11p, 16q, and 18q. These findings suggest that LOH at D17S5 may be involved in the early stage of breast carcinoma development, while INT2 amplification and LOH at 11p, 16q, and 18q appear to be genetic alterations that occur with tumor progression. In addition, as lymph node metastases were significantly related to amplification of the ERBB2 and MYC genes, and LOH of the NME1 gene, these genetic alterations may play a role in the mechanism of lymph node metastases.
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PMID:Analysis of genetic alterations related to the development and progression of breast carcinoma. 790 63

We set out to define the alterations of chromosome 17 in human bladder tumors and to correlate p53 nuclear over-expression with 17p deletions in those neoplasms. We studied 60 bladder tumors by restriction fragment-length polymorphism analysis directed at five different loci on chromosome 17. The same tumors were studied with a panel of mouse monoclonal antibodies (PAb1801, PAb240, and PAb1620) to mutant and wild-type p53 proteins using immunohistochemistry. Deletion of 17p correlated with grade (p = 0.039), stage (p = 0.004), and the presence of vascular invasion (p = 0.056). None of the pathologic parameters correlated with 17q deletions. p53 nuclear overexpression correlated with grade (p = 0.027), stage (p = 0.008), vascular invasion (p = 0.021), and the presence of nodal metastases (p = 0.007). In superficial (Ta) lesions, 17p was not deleted, whereas 55% of T1 and T2-T4 tumors showed a loss of heterozygosity. Mutations of p53 as detected by immunohistochemistry were seen in superficial as well as invasive tumors, whereas loss of heterozygosity was seen only in invasive tumors. A strong correlation was found between the presence of mutation and the loss of heterozygosity of the remaining allele (p = 0.0003). Additional follow-up and further studies are required to better define the role of p53 nuclear overexpression and 17p deletions as markers of tumor progression in human bladder cancer.
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PMID:Molecular genetic alterations of chromosome 17 and p53 nuclear overexpression in human bladder cancer. 790 25

Metastatic phenotype in human solid tumors is believed to follow stochastic acquisition of structural genetic aberrations-so-called multistep tumor progression. We tested this hypothesis in breast carcinoma by immunostaining 89 stage-heterogeneous cases for the products of three genes (p53, ERBB-2, and EGFR) which are frequently altered in this tumor system. Variable relationships were observed between advanced disease stage and immunostaining for individual gene products (ERBB-2 - p = 0.05, EGFR - p = 0.02, p53 - p = 0.12, Chi Square test). Regional or distant metastases at presentation correlated with multiple oncogene/tumor suppressor gene expression abnormalities: node negative -59% none positive, 29% one positive, 12% two or more positive, vs. node positive -37% none positive, 23% one positive, 39% two or more positive (p = 0.01). Only 2/12 (17%) of tumors with distant metastases at presentation were negative for abnormal expression of any of these gene products, and 7/12 (58%) were positive for two or three. Among axillary node negative patients who developed recurrences, 67% exhibited staining for at least one gene product, compared to only 27% of those without recurrences (p = 0.02). All 5 cases with abnormal staining for each gene product had regional or distant metastases at presentation and recurred. In multivariate analysis, individual expression of p53 outweighed expression of ERBB-2 and EGFR in correlation with outcome. These data suggest clinical neoplastic progression of breast carcinomas correlates with cumulative genetic events detectable by protein expression. Short term recurrence, however, may correlate more closely with abnormal expression of p53 than with EGFR or ERBB-2.
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PMID:Concurrent abnormal expression of ERBB-2, EGFR, and p53 genes and clinical disease progression of breast carcinoma. 791 62


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