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 accumulation of p53 protein in the nuclei of cancer cells is known to correlate well with the presence of mutations in the p53 gene. We therefore investigated the immunohistochemical reactivity of the anti-p53 antibody, PAb1801, in specimens taken from 149 cases of primary gastric cancer and processed by acetone fixation, in order to elucidate the incidence and clinicopathological significance of p53 alterations in gastric cancer. Thirty-four out of 99 (34%) advanced gastric cancers and 11 out of 50 (22%) early gastric cancers showed positive reactions in the nuclei. The nuclei of non-cancerous cells, including gastric glandular epithelial cells, however, were not stained. Histopathologically, a nuclear accumulation of p53 protein was seen frequently in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures (43/101, 43%), but was rarely seen in signet-ring cell carcinoma, mucinous adenocarcinoma or poorly-differentiated adenocarcinoma growing in a scattered manner (2/48, 4%). There was no correlation between stainability of p53 protein and clinicopathological features such as depth of tumor invasion, microscopic lymphatic invasion, microscopic venous invasion, nodal involvement and clinicopathological stage in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures. The results suggest papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures to share a common carcinogenetic pathway in which mutation of the p53 gene has an important role to play at a relatively early stage. Additionally, we showed the applicability of immunohistochemical detection of p53 protein in endoscopic biopsy material routinely formalin-fixed. The current method may be of some help in routine practice in discriminating between normal, precancerous and cancer cells in the stomach.
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PMID:High incidence of nuclear accumulation of p53 protein in gastric cancer. 127 44

Overexpression of p53-protein appears to be a common event in primary breast cancer. It has been proposed that the presence of elevated levels of this protein may be an independent prognostic factor and may be important for the ability of a tumor to metastasize. This study was performed to evaluate the influence of immunohistochemically detectable mutant p53-protein on metastasis-free survival of patients with breast cancer. Immunohistochemistry was performed on 117 paraffin-embedded biopsy specimens of consecutive patients with stage T1-T4 breast cancer, using a monoclonal antibody against p53 suppressor gene product. 29 (24.8%) specimens showed positive staining, whereas in 88 (75.2%) a negative staining reaction for p53 was found. Comparing time intervals to diagnosis of metastasis, using Kaplan-Meier curves, Log-Rank test revealed no significant differences in metastasis-free survival between p53 positive and negative patients (P = 0.32), whereas statistically significant differences were noted for tumor stage (P < 0.01), nodal status (P < 0.01), histological grading (P < 0.01) and estrogen receptor status (P = 0.03). Mutant p53-protein, as detected by immunohistochemistry in paraffin embedded tumor tissue, does not appear to influence metastasis-free survival in patients with breast cancer.
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PMID:Immunohistochemical detection of mutant p53-suppressor gene product in patients with breast cancer: influence on metastasis-free survival. 129 80

Cancer is now considered to be a multi-hit process which involves a number of aberrant genetic events culminating in malignant transformation. In squamous cell carcinoma (SCC) of the head and neck the action of both oncogenes and tumour-suppressor genes has been identified during the course of the disease. Cytogenetic analysis of these carcinomas has demonstrated chromosomal breakpoints, particularly in the regions of 1p22 and 11q13 together with frequent amplification of the proto-oncogenes in the 11q13 amplicon; int-2, hst-1 and bcl-1. Ras mutations have been infrequently identified in the Western World whereas ras over-expression has been a common finding and may be associated with the early development of head and neck cancer. C-myc over-expression appears to correlate with a poor prognosis for these patients. The tumour-suppressor gene p53 is also thought to be involved in the development of SCC in head and neck tumours and its aberrant expression is associated with a history of heavy smoking and heavy drinking. E-cadherin, a putative tumour-suppressor gene is down-regulated in poorly differentiated head and neck SCC and maybe important in nodal metastasis. A recent study has indicated that the Human Papilloma Virus (HPV 16 and 33) has a role in the aetiology of tonsillar carcinomas and HPV has been shown to produce transforming proteins which bind to and inactivate the p53 tumour suppressor gene. This evidence suggests that the possibility of a viral mechanism for the development of SCC in the head and neck should be considered. This paper proposes a series of genetic events to explain the development of SCC of the head and neck.
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PMID:Oncogenes and tumour-suppressor genes in squamous cell carcinoma of the head and neck. 133 Jan 49

Inactivation of tumour suppressor genes may be an important aetiological factor in many human cancers including breast. In a study of 197 breast cancer patients, tumour tissue was snap-frozen at the time of surgery and immunohistochemical labelling for p53 protein and retinoblastoma (Rb) gene product carried out using an indirect immunohistochemical technique. Tumours were scored by two independent observers for the intensity of nuclear staining for each antibody. Expression of p53 protein showed a significant association with a shorter time to relapse (P = 0.03) and death (P = 0.02) (log rank test). p53 expression did not correlate with nodal status but showed a significant association with high tumour grade (P = 0.001). Rb gene expression showed no relationship to relapse or survival but loss of expression showed a significant correlation with positive lymph node status. The manner by which these proteins might act to determine tumour behaviour remains to be established.
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PMID:Retinoblastoma and p53 gene expression related to relapse and survival in human breast cancer: an immunohistochemical study. 145 67

This study was undertaken to determine the expression of p53 gene in cytologic specimens from benign and malignant breast lesions. To detect p53 an immunocytochemical assay with p53 (pAb421) monoclonal antibody was used. Abnormalities in p53 expression were found in 19 out of 40 Fine Needle Aspiration (FNA) smears with infiltrating ductal breast carcinomas. Benign epithelial breast cells obtained from fibroadenomas, fibrocystic disease and smears from nipple discharge reacted negatively for p53 in 38 out of 39 cases. Moderate positive reaction, confined to a few clusters of epithelial cells, was observed in one smear of fibroadenoma with cellularity. The results recorded in this study show that no significant association was found between p53 staining and stage of disease, tumor size or nodal status and that the immunocytochemical assay represents a simple method for the detection of p53 associated proteins in breast lesions.
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PMID:p53 expression in cytologic specimens from benign and malignant breast lesions. 174 98

The p53 gene has been implicated as a tumor suppressor gene with mutations found in common human cancers. We examined 51 early stage, primary, resected non-small cell lung cancer specimens using an RNAase protection assay and cDNA sequencing. Mutations changing the p53 coding sequence were found in 23/51 (45%) tumor specimens, but not in the corresponding normal lung, were distributed between codons 132 to 283, and included tumors with and without 17p allele loss. Fifteen of the 23 mutations lay in the predicted binding regions for SV40 large T antigen, and 14 were located in regions highly conserved between species. G to T transversions were a common result of p53 mutations in lung cancer compared to other cancers suggesting exposure to different mutagens. In univariate and multivariate analysis the presence of p53 mutations was associated with younger age and squamous histology. However, the presence of p53 mutations was not significantly associated with tumor stage, nodal status or sex and was found in all histologic types of lung cancer. We conclude that somatic mutations in the p53 gene play an important role in the pathogenesis of early stage non-small cell lung cancer.
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PMID:Mutations in the p53 gene are frequent in primary, resected non-small cell lung cancer. Lung Cancer Study Group. 197 60

A more accurate method of detecting nodal disease in squamous cell carcinoma of the tongue is needed so that treatment of the neck with its associated morbidity can safely be reserved for patients who actually have metastatic disease. Tumor angiogenesis and the expression of the p53 antigen--which have each been shown to be predictive of metastasis in breast and colon cancer, respectively--are examined for their ability to predict neck metastasis in tongue cancer. Fifty-seven patients with T1 and T2 squamous cell carcinoma of the oral tongue, whose neck disease was examined by dissection or by 2-year follow-up, were studied. Twenty-eight patients (49%) were node positive and 29 patients (51%) were node negative. The primary tumors were immunohistochemically stained for the p53 antigen and for factor VIII, which allowed the blood vessels within the tumor to be quantitated. The mean vessel counts per x200 high-power field were 59.8 and 61.5 for node-positive and node-negative patients, respectively (p = 0.8). Node-positive patients showed overexpression of p53 43% of the time, vs. 61% for node-negative patients (p = 0.17). Multivariate analysis confirmed that no difference in tumor angiogenesis or the expression of the p53 antigen was found between tumors that had metastasized and those that had not. Therefore neither tumor angiogenesis nor the p53 tumor marker is clinically useful in determining lymph node metastasis in these patients.
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PMID:Tumor angiogenesis, the p53 antigen, and cervical metastasis in squamous carcinoma of the tongue. 752 5

Among extranodal non-Hodgkin's lymphomas, primary cutaneous lymphomas (CLs) represent a consistent group of B- and T-cell malignancies. We investigated the arrangement of Ig and T-cell receptor (TCR) genes, together with the involvement of several oncogenes and the tumor-suppressor gene p53, in a panel of primary cutaneous B- and T-cell lymphomas (CBCLs and CTCLs). Southern blot analysis was performed to detect rearrangements of the Ig, c-myc, bcl-1, bcl-2, bcl-3, bcl-6, and the NFKB2/lyt-10 genes in 52 cases of CBCLs and of the TCR, bcl-3, and NFKB2/lyt-10 genes in 38 cases of CTCLs. tal-1 gene deletions were analyzed in CTCLs by means of polymerase chain reaction (PCR). p53 gene mutations were assayed using PCR, single-strand conformation polymorphism analysis, and direct DNA sequencing in CBCL and CTCL cases. Clonal rearrangements of Ig genes or oncogenes were found in 25 of the 52 CBCLs. In particular, we detected rearrangements of the bcl-1 locus (2 cases), the bcl-2 gene (2 cases), the NFKB2/lyt-10 gene (2 cases), and the bcl-6 gene (1 case); interestingly, 4 of these cases showed a germline arrangement of the Ig genes. Clonal rearrangements of TCR genes were detected in 37 of the 38 CTCLs. Rearrangements of the NFKB2/lyt-10 gene were present in 2 cases and tal-1 gene deletions in 3 CTCL cases; p53 gene mutations were detected in 1 CTCL case. Overall, our data indicate that (1) clonal rearrangement of Ig genes is frequently undetectable by means of Southern blot in CBCLs (60%); (2) genetic lesions are involved in a limited but significant fraction of primary CLs showing a molecular marker of clonality (13/62; 20%); and (3) rearrangements of the bcl-1, bcl-2, or bcl-6 loci, associated with specific subsets of nodal lymphoid neoplasias, are rarely observed in CBCLs. Moreover, our results suggest that tal-1 gene deletions may play a pathogenetic role in non-acute T-cell malignancies and that, in the context of lymphoid malignancies, CLs may represent a favorable target for the possible oncogenic potential of the NFKB2/lyt-10 gene.
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PMID:Molecular analysis of cutaneous B- and T-cell lymphomas. 757 11

P53 immunohistochemical detection using DO7 antibody on 942 cases of previously untreated breast invasive ductal carcinoma (IDC) with a median follow up of 117.9 months (89 to 160) was performed. Three hundred and three (32%) tumors were positive. All positive tumors were taken into account, positivity ranging from 1 to 100% of tumoral cells. The Chi square test showed significant negative correlation between p53 positivity and age (p = 0.01), estrogen receptor status (p < 0.0001), and progesterone receptor status (p = 0.0005), and significant positive correlation with tumor grade according to the Scarff, Bloom and Richardson system (SBR Grade) (p < 0.0001). There was no significant association with tumor size or nodal status. Concerning the univariate analysis, in the whole group and node-positive group (n = 544) p53 positivity was highly significant for overall survival (OS) (p < 0.0001 and p = 0.0003), disease-free interval (DFI) (p = 0.0001 and p = 0.0005), and metastasis-free interval (MFI) (p < 0.0001 and p = 0.0003). In the node-negative group (n = 398), p53 was significant with respect to OS (p = 0.01) and DFI (p = 0.04). P53 positivity came out as an independent prognostic parameter in the multivariate analysis in the whole group and the node-positive group, though of minor significance compared to axillary lymph node status, SBR grade, progesterone receptor status and tumor size.
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PMID:Prognostic value of p53 in breast invasive ductal carcinoma: an immunohistochemical study on 942 cases. 757 9

Present methods of predicting nodal progression preoperatively in patients with non-small cell lung cancer (NSCLC) are inadequate. Our hypothesis was that p53 expression in primary NSCLC would predict disease progression, making it a useful marker of adverse outcome. From 1987 to 1992, sixty-eight consecutive NSCLC patients underwent potentially curative lung resection and mediastinal lymph node dissection by one surgeon. Primary tumours were analysed using the p53 monoclonal antibody 1801. p53 overexpression was found in 53% of tumours. p53 expression did not correlate with age, gender, histology or stage. A trend toward a higher incidence of p53 expression was seen in tumours with nodal spread (P = 0.06), and p53 expression correlated significantly (P = 0.03) with improved disease-free survival in patients with squamous cell carcinoma (SCC). p53 was the fourth most important independent predictor of survival, behind histology, gender and nodal disease. As a weak independent predictor of survival, the correlation of p53 expression with survival in patients with SCC must be evaluated with caution. If borne out in a larger patient population, p53 expression may be a marker of nodal disease progression in patients with NSCLC.
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PMID:p53 and disease progression in patients with non-small cell lung cancer. 758 88


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