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 prognostic value of the immunohistochemical expression of p53 was evaluated in 133 patients with pancreatic cancer. Formalin-fixed paraffin-embedded specimens of ductal pancreatic adenocarcinomas retrieved at the time of operation were stained with the monoclonal antibody DO-7. Approximately half of the tumors (47%) showed a high level of p53 immunoreactivity (> or = 20% positive nuclei). No correlation was demonstrated between the level of p53 immunoreactivity and age of the patient, gender, TNM stage, resectability or site of the tumor. A high level of p53 staining was seen in a slightly smaller proportion (30%) of patients with well-differentiated tumors than in patients with moderately (50%) or poorly differentiated (50%) tumors, but the difference was not significant. In a multivariate survival analysis, stage, grade and postoperative chemotherapy emerged as independent prognostic factors. Surgical resectability, if entered instead of stage as a variable in a separate Cox model, predicted prognosis independently. In univariate analysis, the site of the tumor was also a significant prognostic variable. However, no association between the level of p53 immunoreactivity and survival in either uni- or multivariate analysis was found.
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PMID:Prognostic value of immunohistochemical expression of p53 in patients with pancreatic cancer. 860 35

It has been suggested that the interaction of cytomegalovirus (CMV) with the p53 tumor suppressor gene product plays a role in the development of coronary artery restenosis after angioplasty. CMV nucleic acids have been observed in the coronary arteries of allografted hearts, suggesting a possible role for the interaction of CMV with p53 in the development of accelerated graft arteriosclerosis in transplant recipients. Formalin-fixed, paraffin-embedded sections of coronary arteries from 19 transplanted hearts were immunostained for the p53 gene product using Target Unmasking Fluid (TUF)-mediated immunohistochemistry and the anti-p53 antibodies CM1 and DO7. Fresh-frozen sections of coronary arteries were also available from six of the 19 hearts, and these fresh-frozen sections were immunostained for the p53 gene product with the DO7 antibody and for WAF1 using the anti-WAF1 antibody EA10. Focal and weak staining for p53 was observed in smooth muscle and endothelial cells in two of 19 vessels, whereas the remaining 17 did not stain. CMV nucleic acids were previously shown in six of 13 of these hearts by in situ hybridization. The fresh-frozen sections of coronary arteries also did not stain for p53, but the smooth muscle cells in these vessels did stain intensely for WAF1. These results suggest three possibilities: (1) CMV-p53 interactions are not important in the development of accelerated graft arteriosclerosis; or (2) there is an interaction, but it is transient and not detectable at the time points examined in this study; or (3) there is an interaction, but binding of CMV to p53 leads to accelerated degradation of p53, as occurs with HPV-E6. The expression of WAF1 further suggests that the WAF1-mediated antiproliferative signal is intact in these vessels.
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PMID:The WAF1-mediated p53 growth-suppressor pathway is intact in the coronary arteries of heart transplant recipients. 861 73

The prognostic value of overexpression of the p53-encoded protein was evaluated in 242 patients with gastric cancer. Formalin-fixed paraffin-embedded specimens of gastric adenocarcinomas were stained with the monoclonal antibody DO-7. 95 patients (39%) showed a high level of immunoreactivity (> or = 20% of cell nuclei staining positively), suggesting the presence of a mutation in the TP53 coding sequence. Overexpression of the p53 protein correlated significantly with stage of disease (P = 0.01), the presence of distant metastases (P = 0.04) and with the intestinal type of cancer (P = 0.04). No correlation between p53 overexpression and age, gender or the presence of the lymph node metastases was found. In univariate analysis, p53 immunoreactivity correlated significantly with survival (P = 0.0005). The median survival in the p53 high-level group was 19 months compared with 65 months in the p53 low-level group. In multivariate analyses, stage of disease and the presence of distant metastases emerged as independent prognostic factors, whereas p53 immunoreactivity did not (P = 0.08). The present results indicate that overexpression of the p53 protein is not an independent prognostic factor in patients with gastric cancer.
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PMID:Expression of p53 protein as a prognostic factor in patients with gastric cancer. 866 30

Adenoid cystic carcinoma (ACC) is a malignant tumor of salivary gland origin having a propensity for spread by direct extension or perineural invasion with frequent recurrences. Previous reports have shown that tumor behavior is not always predicted by histological pattern or stage. Little is known of the role of p53 tumor suppressor gene mutation and altered protein expression with respect to ACC pathobiology and recurrence. The authors analyzed a group of 14 ACC specimens (seven primary; seven recurrent) from 13 patients treated between 1987 to 1993. Formalin-fixed, paraffin-embedded specimens were reviewed and subjected to, immunohistochemistry (p53, DO-7, DAKO, Nutley, NJ; and WAF-I, Ab-1, Oncogene Sciences, Uniondale, NY) on 4-microm-thick histological sections as a prelude to p53 genotyping. In one case, sequential material representing primary and recurrent tumor was analyzed. Each tumor specimen was topographically genotyped for p53 point mutational change. Minute tissue samples were removed from unstained sections, polymerase chain reaction (PCR) amplified for p53 exons 5 to 8, and then underwent direct DNA sequencing. Six of seven primary ACCs were p53 immunostain negative. Four of seven recurrent (57%) ACCs were p53 immunopositive. These tumors showed varying degrees of p53 immunopositivity ranging from diffuse, intense staining of most tumor cells (n = 1) to interspersed, strongly positive cells mixed with predominantly p53 immunonegative cells (n = 4). All tumors were WAF-I immunostain negative. Two of the most immunopositive recurrent tumors each manifested a single type of p53 point mutation detected by p53 DNA genotyping (p53 exon 5:codon 175 and p53 exon 6:codon 199). In the case in which both primary and recurrent tumor was available, only the recurrent tumor contained point mutational damage. Negative immunostaining for p53 in primary ACC suggests that p53 mutation is not important in early events involving development of this tumor. In contrast, the frequent presence of p53-positive cells and the detection of point mutations in recurrent ACC suggests that p53 alterations are involved in later stages of tumor progression, important in the phenomenon of ACC recurrence.
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PMID:The role of p53 mutation and protein expression in primary and recurrent adenoid cystic carcinoma. 866 66

P53 immunohistochemistry in astrocytic tumors has usually been evaluated by the percentage of positive cells. However, in this study we analyzed the P53 immunopositive cells by their patterns of distribution. Formalin-fixed and paraffin-embedded sections from 38 patients with astrocytic tumors were examined. The distribution pattern of P53 immunostaining cells was divided into 3 types: negative, locally scattered, and diffuse clustering. There were 2 positive stains in 5 astrocytomas (40%), 12 positive in 24 anaplastic astrocytomas (50%), and 7 positive in 9 glioblastoma multiformes (78%). In astrocytomas, the positive cells were locally scattered. In anaplastic astrocytoma and GBM, the positive cells appeared locally scattered or as diffuse clustering. For the variant immunoreactive expression, the mean ages for patients with negative, locally scattered and diffusely clustered P53 immunostaining were as follows: 51.4, 52.6, and 28.4 years (P < 0.01), respectively. In anaplastic astrocytoma and GBM, the diffusely clustered pattern was more common in younger patients, whereas elderly patients in same groups tended to have few or no P53 immunopositive cells. Thus, our results implicate that clonal expansion of P53 immunopositive cells is associated with brain tumor progression.
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PMID:Immunohistochemical pattern of P53 protein in human astrocytic tumors. 867 33

The aim of our study was to examine the prognostic significance of p53 protein accumulation and gene mutation in a series of 116 gastric carcinomas from a low incidence population. Formalin-fixed, paraffin-embedded tumour sections were used to investigate p53 protein accumulation by immunostaining with monoclonal antibody (MAb) DO-7 and p53 gene mutation by single-strand conformation polymorphism analysis of exons 5-8. Nuclear p53 accumulation was detected in 23% of tumours and mutation in 28%. Concordance between the 2 alterations was observed in 73% of cases. p53 protein accumulation was more frequent in tumours with lymph node metastasis, while p53 mutations were more frequent in tumours from older patients. The histopathological parameters of depth of invasion, grade and histological type showed no significant associations with either p53 alteration. In univariate analysis, both alterations were associated with significantly shortened patient survival. The 5-year survival rate for patients with a p53 mutation was 9% compared to 42% for those without a mutation. In multivariate analysis adjusted for the other histopathological parameters, p53 gene mutation but not immunohistochemically-detected p53 protein accumulation was an independent prognostic indicator of poor survival in gastric carcinoma.
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PMID:p53 accumulation and mutation are prognostic indicators of poor survival in human gastric carcinoma. 868 88

The expression of the nm23-H1 gene has been suggested to have an inverse association with metastases in certain tumours. The aim of this study was to investigate the relationship of nm23-H1 immunohistochemical expression with pathological tumour variables and survival in a series of transitional cell carcinomas (TCCs) of the bladder. Formalin-fixed, paraffin-embedded archival tissue from 87 carcinomas (Ta-T1 45 cases) and T2-T4 (42 cases) was immunostained (Strept ABC/HRP) with the NDPK-A monoclonal antibody (NDPK-A) against nm23-H1 protein. The tumours had already been evaluated for immuno-expression of p53 protein. In addition, DNA analysis was performed by flow cytometry. Results were analysed using the linear trend in proportions test, the Fisher's exact test and multivariate analysis. Paradoxically, advanced tumour stage showed significant correlation with nm23-H1 immunopositivity in muscle invasive TCCs (P(t) = 0.01). Patients with nm23-H1 positive, muscle invasive TCCs had a worse prognosis at a level of suggestive statistical significance (PF = 0.08). In multivariate analysis, using a Cox's proportional hazards survival model with six variables, tumour grade, disease stage and synchronous p53 and nm23-H1 detection showed significant correlation with poor patient survival (P = 0.014, P = 0.049 and P = 0.05, respectively).
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PMID:Immunohistochemical evaluation of nm23-H1 gene product in transitional cell carcinoma of the bladder. 873 18

The aims of this study were to analyse the expression of p53 by immunohistochemistry in a range of malignant and pre-malignant conditions and to assess the degree of inter-observer variability in interpretation of p53 immunostaining. Formalin-fixed paraffin-embedded sections from 28 colorectal carcinomas (CRC), 40 cervical intraepithelial neoplasia lesions (CIN), 22 transitional cell carcinomas of the bladder (TCC), 10 invasive squamous carcinomas of uterine cervix and 21 squamous cell carcinomas of skin were examined. A polyclonal antibody was used in 90 cases. A monoclonal antibody was used in the remainder. Ten cases were stained with both. Aberrant expression of p53 protein was documented in 48% of squamous cell carcinomas of skin, 29% of CRC, 22% of CIN and 23% of TCC. All cases of squamous cell carcinoma of uterine cervix were negative. Inter-observer variation occurred in 7% of cases examined. This was confined to two tumour groups, TCC and CIN. Our results showed that p53 oncoprotein expression by immunohistochemistry was identified in 26% of cases but the range was wide (0-48%) and appeared to be tumour specific. Inter-observer variability in the interpretation of immunohistochemical staining was low (7%) and was restricted to two tumour groups.
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PMID:Inter-observer variation of p53 immunohistochemistry--an assessment of a practical problem and comparison with other studies. 875 86

Ovarian serous tumors of borderline malignancy frequently show morphologically benign and borderline areas within the same tumor. This study was undertaken to determine if these two morphologically disparate areas differ in their proliferative activity and p53 expression. Formalin-fixed, paraffin-embedded archival tissue from 17 ovarian serous borderline tumors with morphologically benign and borderline areas were immunostained with monoclonal antibodies against p53 and MIB1. The percentage of positive cells was determined by counting 100 consecutive cells for each stain in the most intensely stained areas in morphologically benign and borderline portions of these tumors. There was a significantly increased proliferation (MIB1 expression) in borderline areas compared with benign areas (37.05 +/- 15.3 versus 12.88 +/- 6.7, p = 0.0001). More than 30% of cells were positive for MIB1 in 13/17 borderline areas compared with none of the 17 benign areas (p < 0.0001). The expression of p53 was also higher in borderline areas compared with benign areas (7.12 +/- 8.8 versus 2.94 +/- 4.46, p = 0.0078). More than 10% of cells were p53 positive in 5/17 borderline areas compared with 1/17 benign areas (p = 0.08). However, there was no significant correlation between p53 expression and MIB1 expression in either the benign or borderline areas (p = 0.4 and 0.2, respectively). In summary, morphologically borderline areas show significantly higher p53 expression and proliferation compared with morphologically benign areas in ovarian serous borderline tumors. Alterations of p53 may play a pathogenetic role in some ovarian serous borderline tumors. The lack of correlation between p53 expression and MIB1 expression, however, suggests involvement of other factors, in addition to p53, in determining the proliferative rate of ovarian serous borderline tumors.
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PMID:Comparison of p53 and MIB1 expression in benign and borderline areas of ovarian serous tumors. 885 45

The p53 gene, which is located on human chromosome 17, encodes for a nuclear phosphoprotein and is thought to regulate cell growth and proliferation. Although the immunoreactivity for p53 oncoprotein in transitional cell carcinoma (TCC) of the urinary bladder has been shown to correlate with clinicopathologic findings and prognoses, there have been no such reports on TCC of the upper urinary tract (TCC-UUT). The present study investigated the prognostic value of p53 oncoprotein in TCC-UUT. Formalin-fixed, paraffin-embedded tumor tissues from 149 TCC-UUT patients were analyzed using immunohistochemical staining. Immunohistochemically, p53 oncoprotein was recognized as positive in 26.8% of the samples. The immunoreactivity for p53 oncoprotein was significantly (P < .05) correlated with both stage, grade, and pattern of growth. The 5-year disease-free and overall survival rates were 58.4% and 69.7%, respectively. A univariate analysis of survival showed that stage, grade, pattern of growth, and the immunoreactivity for p53 oncoprotein have a significant effect on disease-free and overall survival rates. In the final models of multivariate analysis, only stage for disease-free survival, and stage and the immunoreactivity for p53 oncoprotein for overall survival were found to be progressive or prognostic factors. Detection of immunoreactivity for p53 oncoprotein appears to be of real value in deciding the prognosis of TCC-UUT.
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PMID:Immunohistochemical evaluation of p53 oncoprotein in transitional cell carcinoma of the upper urinary tract. 895 8


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