Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Fine needle aspiration biopsy (FNAB) is a well established method for diagnosing breast lesions, including cancers. FNAB does not require surgery and uses only a small amount of material. FNAB can also be used to acquire material for special studies. This is especially useful with small tumors (< or = 1 cm) when most of the material is needed to make a histologic diagnosis. Immunostaining techniques can be used on FNABs to investigate proliferation by bromodeoxyuridine uptake or Ki-67 labeling. Immunostaining techniques can also be used to identify oncoprotein expression, such as of p53. Fluorescence in situ hybridization is a technique that can be used to gather cytogenetic information directly from interphase tumor cells and is well suited for use with FNAB material because the harvested nuclei are intact and no cumbersome dissociation processing is needed. Flow cytometric techniques can be applied to FNAB material to study DNA content and S-phase fraction. Material acquired by FNAB can also be analyzed by the polymerase chain reaction followed by mutation detection. In this report, the authors show the applicability of these various analytic approaches to FNAB material from primary breast cancers. They show that it is essential that the FNAB harvest is representative, ample, and well prepared for the success of these studies.
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PMID:Fine needle aspiration techniques for the characterization of breast cancers. 803 33

p53 is a tumor suppressor gene, located in the short arm of chromosome 17, which encodes for a nuclear protein involved in the control of cellular growth. Mutations in p53 gene are the most common genetic alterations in a several human cancers, including Non Small Cell Lung Cancer (NSCLC). However, up to now, the role of p53 in the tumour's behaviour and its progression has not been completely clear. We performed immunohistochemical staining for mutated p53 using two monoclonal antibodies, PAb1801 and PAb240, in fresh tumour specimens from 103 consecutive patients who underwent surgery for resectable NSCLC. PAb1801 detects both the normal and mutant form of p53, while PAb240 is specific only for the mutant form and recognizes a denaturation-resistant epitope located between aminoacids 156-335. Both antibodies showed a mainly nuclear staining in neoplastic cells but not in surrounding uninvolved lung tissues. 68 out of 100 (68%) and 37 out of 103 (35.9%) of the cases were positive with PAb1801 and with PAb240, respectively. Tumours from patients with hilar-mediastinal lymph node involvement showed a higher p53 expression, detected by PAb1801, than those without nodal metastases (p = 0.04). Moreover, tumours expressing more than 60% of positive cells with both antibodies showed a significant increase of nodal involvement (p = 0.1; p = 0.03). Furthermore, p53 expression was significantly related to post-surgical stage (p Tumor Stage) (p = 0.04). In addition, we did not find any correlation between p53 expression and proliferating activity evaluated by PCNA, Ki-67 and DNA flow cytometric cell cycle. In conclusion, the evaluation of p53 oncogene expression may identify individuals whose resectable NSCLCs have a more aggressive tumour behaviour.
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PMID:p53 expression in non small cell lung cancer: clinical and biological correlations. 810 Apr 13

Strong immunohistochemical reactivity for p53 tumor suppressor gene product has been reported in a variety of different human malignancies including CD30- (Ki-1) positive anaplastic large cell lymphoma (ALCL). Although high levels of p53 protein have been interpreted as abnormal, rapidly proliferating benign and neoplastic lymphoid cells may have increased p53 expression in the absence of structural alterations. On the other hand, mutations in the p53 gene can lead to a lack of p53 protein production. Structural alterations of the p53 gene have not been documented in cases of ALCL and the mechanism for an abnormal pattern of p53 expression in these lymphomas has not been elucidated. Therefore, to determine whether an altered pattern of p53 expression correlates with mutations in the p53 locus in ALCL, we analyzed the expression of p53 protein immunohistochemically, compared it with the proliferation index using monoclonal antibody Ki-67, and assessed the presence of mutations in exons 5 though 9 of the p53 gene using a single-strand conformation polymorphism assay in a panel of 17 ALCLs. Furthermore, we studied the presence of allelic deletions of chromosome 17p by restriction fragment length polymorphism analysis. We found significant levels of p53 protein expression in 12 of the 15 cases studied, but identified mutations in only one of 17 cases. An allelic deletion in chromosome 17p was identified only in the one case containing a mutated p53 gene. Whereas the case containing structural alterations in the p53 gene did have strong p53 immunoreactivity, 11 cases that lacked p53 mutations in the regions examined also had significant levels of p53. Thus, our studies indicate that strong immunohistochemical reactivity for p53 is not a reliable indicator of the presence of structural alterations of p53 gene exons 5 through 9 in ALCL.
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PMID:High levels of p53 protein expression do not correlate with p53 gene mutations in anaplastic large cell lymphoma. 810 95

We recently demonstrated that only one of 36 T-cell neoplasms contained p53 gene mutations. Although p53 gene mutations are known to result in overexpression of the p53 gene product, we also recently discovered that p53 protein overexpression does not correlate with p53 gene mutations, but does correlate with proliferation (r = 0.92), in anaplastic large cell lymphoma. In view of these findings, we investigated 34 non-human T-cell lymphotropic virus type I (HTLV-I) related postthymic T-cell lymphomas immunohistochemically for p53 protein, using monoclonal antibody 1801, and for proliferation, using monoclonal antibody Ki-67, and quantitated the results with the CAS-200 computerized image analysis system. We evaluated the presence of mutations in conserved exons 5 to 9 of the p53 gene using single-strand conformation polymorphism analysis and DNA sequencing. p53 mutations were detected in three of 34 cases, including two that contained deletions. p53 protein overexpression was detected in 17 of 34 cases, including the three mutated cases, with reactivities ranging from 10% to 48%. However, many cases in which a structural alteration could not be detected demonstrated levels of p53 protein expression comparable to those cases that were mutated. Correlation of p53 protein expression and proliferation, as assessed by Ki-67 expression, in this group of lymphomas was poor (r = 0.34). Whether alternative mechanisms of p53 protein inactivation are causing phenotypic overexpression of the p53 protein in these malignant lymphomas is unknown, although preliminary studies do not support a major role for such mechanisms. Therefore, the etiology and the significance of p53 protein overexpression in the cases that lack a demonstrable mutation is unclear. Nevertheless, as in anaplastic large cell lymphoma, overexpression of the p53 gene product is not a reliable predictor of the presence of mutations in conserved portions of the p53 gene in non-HTLV-I associated post-thymic T-cell lymphoma.
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PMID:Post-thymic T cell lymphomas frequently overexpress p53 protein but infrequently exhibit p53 gene mutations. 812 43

We have investigated the occurrence of chromosomal DNA and cell cycle-related protein changes in Barrett's epithelium and adenocarcinoma. The presence of numerical chromosomal aberrations was studied by applying nonisotopic in situ hybridization (ISH) with (peri-)centromeric DNA probes, specific for chromosomes 7, 8, 17, and Y, to routinely processed tissue sections of five cases (4 male, 1 female) of Barrett's adenocarcinoma and adjacent Barrett's epithelium. Cell cycle-related protein expression was studied by immunohistochemistry (IHC) for p53 protein and the Ki-67 antigen (Mib-1) in subsequent sections. P53 protein overexpression was found in 3 of the 5 tumors. Overrepresentation of chromosome 8 and loss of chromosome 17 were found in 2 adenocarcinomas, both also negative for p53 protein overexpression. Y-loss, mostly clonal, was detected in 3 of the 4 male adenocarcinomas and 2 cases of adjacent Barrett's epithelium. One tumor had both areas of overrepresentation and loss of the Y chromosome. All Barrett's adenocarcinomas appeared to contain aneuploid cell populations. No relation was found between cell proliferation characteristics and chromosomal aberrations. We conclude that ISH with chromosome specific DNA probes can be applied for the assessment of potentially important numerical chromosome changes in Barrett's esophagus. Further, the combination of IHC and ISH is useful for evaluation of specific genetic events.
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PMID:Detection of genetic changes in Barrett's adenocarcinoma and Barrett's esophagus by DNA in situ hybridization and immunohistochemistry. 816 5

The proliferative activity and the origin of multinucleated Reed-Sternberg cells and mononuclear variants in Hodgkin's disease have been studied in the past using several techniques. The presence of both proliferating-cell nuclear antigen and the cell-proliferation-associated antigen Ki-67 have also been reported in Hodgkin's disease. P34cdc2 is the protein product of the cell-cycle-control cdc-2 gene. Using a monoclonal antibody against the protein p34, cases of three different histological subtypes of Hodgkin's disease have been studied along with normal tonsil and follicular lymphoma as controls. In all these cases of Hodgkin's disease, positive p34 staining was seen in the majority of Reed-Sternberg cells and mononuclear variants (> 80%), along with a proportion of small lymphocytes, mainly T cells. Staining was predominantly cytoplasmic and occasionally additional nuclear signals were apparent. In two cases, double immunostaining with the anti-p34 antibody and CM-1 for p53 demonstrated positive signals for both proteins within the same neoplastic cells. Although the presence of p34 in Reed-Sternberg or variant cells reflects mitosis and hence suggests proliferation, the possibility of endomitosis remains and may explain the multinucleated appearance of Reed-Sternberg cells.
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PMID:Proliferation of Reed-Sternberg cells and variants in Hodgkin's disease. 817 8

Epithelial ovarian tumors of varying malignancy as well as normal ovaries were examined for their expression of p53 with the monoclonal antibody PAb1801. Immunohistochemical detection of p53 protein is possible when the gene has been mutated, but not when the normal gene product alone is present. Our results indicate that this tumor suppressor gene may be involved in tumorigenesis, as its expression was detected in both borderline and malignant tumors while normal ovaries and benign ovarian tumors were unstained with the p53 antibody. The presence of p53 was also related to dissemination of disease, residual tumor bulk, and poor differentiation as well as the presence of the proliferation variable Ki-67, another negative prognostic variable. No significant relation could be detected to S-phase fraction or DNA ploidy. Furthermore, the presence of p53 in malignant epithelial ovarian tumors was related to significantly decreased patient survival, with only 36% alive compared to 70% in the p53-negative group (P = 0.002). In the subgroup of patients with residual tumor burden after surgery, those with p53-positive tumors had a significantly (P = 0.05) decreased survival compared to those with p53-negative neoplasms, which further supports an independent role in ovarian cancer malignancy.
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PMID:p53 expression in epithelial ovarian neoplasms: relationship to clinical and pathological parameters, Ki-67 expression and flow cytometry. 820 2

The effects of regional heterogeneity on the accuracy of histological grading of gliomas are well known, but little has been reported about its implications for other diagnostic modalities. This study investigated the relationships of regional heterogeneity in tumor proliferative activity, measured by Ki-67 labeling indices (LI), and histological grades for 16 regionally sampled glioma resections. There was a strong correlation between histological grades and Ki-67 LI in individual regions (p < 0.001), and both methods demonstrated comparable heterogeneity. Heterogeneity increased with tumor grade, probably as an expression of the increased genetic instability that accompanies tumor progression. Similarly, regions with comparable proliferative activity tended to cluster, paralleling clonal expansion. Thus, both histological grading and Ki-67 LI are subject to heterogeneity-induced sampling errors that limit their diagnostic accuracy, particularly in small biopsies. However, fewer grading errors occurred when using both methods together than when using either method alone, suggesting that the use of multiple techniques may reduce the adverse effects of regional heterogeneity on diagnostic accuracy. Regional heterogeneity appears to be a ubiquitous feature of gliomas: it also has been reported in karyotype, p53 oncogene mutations, and PDGF and EGFR expression. The effects of regional heterogeneity on new methods for studying gliomas need to be considered.
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PMID:Regional heterogeneity in the proliferative activity of human gliomas as measured by the Ki-67 labeling index. 822 80

Among 843 cases of breast cancer, p53 oncoprotein was detected by the monoclonal antibody (MoAb) Pab-1801 in only 13%. Low-grade carcinomas (tubular, mucinous, papillary, and invasive cribriform types) did not express p53 protein, but it was observed in 4.2% of infiltrating lobular carcinomas (6 of 140 cases) and 50% of pure medullary carcinomas (5 of 10 cases). In intermediate-grade neoplasms, no correlation was seen between p53 status and other putative determinants of a poor prognosis. The latter included high tumor stage, lymph nodal involvement, high growth fraction (as determined by labeling with the MoAb Ki-67), negative results for estrogen receptor (ER) and progesterone receptor (PR) proteins, and amplification of the c-erbB-2 oncogene product in the neoplastic cells. Ninety-nine of 640 (15.5%) cases of high-grade, invasive, ductal breast carcinoma, however, showed an inverse relationship between expression of p53 protein and positive results for ER/PR proteins and a direct correlation with large tumor size, Ki-67-determined growth fraction, and amplification of c-erbB-2 oncopeptide. All of the latter associations were highly significant statistically. The authors conclude that mutant p53 protein may serve a prognostic role in a subset of cases of invasive ductal mammary carcinoma.
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PMID:Relationship between p53 expression and other prognostic factors in human breast carcinoma. An immunohistochemical study. 837 28

A polymerase chain reaction-single strand conformation polymorphism assay was used to assess p53 mutations in 148 invasive breast carcinomas, selected on the basis of their histotype. They comprised 56 lobular, 47 ductal, 19 mucinous, 18 medullary, and 8 papillary carcinomas. The distribution of p53 mutations was significantly different (P = 0.006) in the histotypes examined: mutations were frequent in medullary (39%) and ductal (26%), less common in lobular (12%), and absent in mucinous and papillary carcinomas. The frequency of mutations in the exon 5 of the p53 gene was significantly higher in medullary carcinomas than in the other histotypes: 5 (63%) of the mutations found in exon 5 were observed in medullary carcinomas (P = 0.012). One hundred twenty-two tumors from the total were also examined by immunohistochemistry for p53 overexpression using antibody PAb 1801. A specific immunostaining in neoplastic cells was present in 12 tumors. A strong correlation (P < 0.001) was observed between p53 mutations and nuclear accumulation of the p53 protein: 10 tumors were scored positive for both p53 mutation and overexpression. However, in 9 cases having a mutated p53 gene we failed to find a positive immunoreaction. A significant association (P = 0.01) was present between mutations in the p53 gene and high proliferative activity of the tumors determined by immunohistochemistry with monoclonal antibody Ki-67. Moreover, a significantly higher expression of the Ki-67 antigen was found in medullary carcinomas compared to the other histotypes. Our findings indicate that in invasive breast carcinomas structural abnormalities of the p53 gene are mainly seen in medullary and ductal tumors and that the other histological types, especially those associated with a high level of differentiation and favorable prognosis, show a very low incidence of p53 mutations.
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PMID:p53 mutations and histological type of invasive breast carcinoma. 840 44


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