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 present study compared two microwave based antigen-retrieval solutions in their ability to unmask antigenic determinants in formalin-fixed and paraffin-embedded tissues for Immunostaining. In this regard, two widely used antigen-retrieval solutions, namely 0.05 M glycine-HCl buffer, pH 3.6, containing 0.01% (w/v) (EDTA) and 0.1 M sodium citrate buffer, pH 6.0, were evaluated for (1) their effectiveness in unmasking a wide range of antigenic determinants (2) their ability to yield reproducible results (3) the lack of deleterious effects in any antibody antigen systems of interest. Both of these antigen-retrieval solutions resulted in greatly improved immunostaining following microwave-heating of dewaxed tissue sections for 2 x 5 min. Glycine-HCl buffer solution resulted in stronger immunostaining with antibodies to nuclear antigens [androgen receptor (AR), estrogen receptor (ER), progesterone receptor (PR), p53, proliferating cell nuclear antigen (PCNA), Ki-67 and MIB-1], cytoplasmic antigens (actin and factor-VIII) and cell-surface antigens [Cu-18, epithelial membrane antigen (EMA) and MT-1 (CD43)], whereas sodium citrate buffer yielded superior immunostaining with antibodies to vimentin, and some cell-surface antigens [common leukocyte antigen (CLA) (CD45) and UCHL-1 (CD45RO)]. The effect of unmasking the epitopes recognized by antibody to PCNA was equally effective with either of the antigen-retrieval solutions. Antibodies to pan-keratin, prostatic acid phosphatase (PAP), B lymphocyte antigen (BLA.36, CD20CY) and L26 (CD20) exhibited no enhancement in the intensity of staining with either of the antigen-retrieval solutions.
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PMID:Comparison of two microwave based antigen-retrieval solutions in unmasking epitopes in formalin-fixed tissue for immunostaining. 754 61

To examine the suggested biological difference between Japanese and British gastric cancers, immunohistochemistry was used to demonstrate eight markers of biological activity in a matched series of 40 Japanese and 33 British cases. There were no differences in the proportions of Japanese and British tumours positive to epidermal growth factor, epidermal growth factor receptor, transforming growth factor alpha, cripto or p53. A significantly greater proportion of British tumours were positive to c-erbB-2 whilst a significantly greater proportion of Japanese tumours were positive to nm23. British tumours had a significantly greater mean proliferating cell nuclear antigen proliferation index than Japanese tumours. These differences could be clinically significant.
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PMID:Are Japanese and European gastric cancer the same biological entity? An immunohistochemical study. 754 52

A series of 26 malignant peripheral nerve sheath tumours (MPNST) and 24 benign peripheral nerve sheath tumours (BPNST) were analysed immunocytochemically for p53 expression and the cell proliferation markers proliferating cell nuclear antigen (PCNA) and Ki67 (with MIB1). In 23/26 MPNST, 5%-65% of the tumour cell nuclei were immunoreactive for Ki67 with MIB1 while none of the 24 BPNST had nuclear staining exceeding 5%. Greater than 50% nuclear PCNA staining was detected in 25/26 MPNST compared with 8/24 BPNST; 17/26 MPNST showed 5-100% nuclear staining for p53 (13/26 > 20%), whereas none of the BPNST had nuclear staining exceeding 1%. The Ki67, PCNA and p53 immunostaining results correlated significantly with benign versus malignant (P < 0.001, P < 0.001 and P < 0.005, respectively) as well as mitotic rate (P < 0.001, P < 0.05 and P < 0.05). Ki67 immunostaining results correlated significantly with PCNA and p53, as did p53 and Ki67 and PCNA (P < 0.001 in both). Stepwise (logistic regression forward) multivariate analysis of the variable, benign versus malignant, revealed the strongest correlations with PCNA (P = 0.007) and Ki67 (P = 0.021). Direct confirmation of the presence of p53 protein was obtained by western blot analysis of 3 MPNST and 5 BPNST. Two MPNST, showing 90% and 30% immunoreactivity, were positive for p53, while one MPNST with 5% immunoreactivity and all 5 BPNST were negative. Southern blot analysis performed on the two MPNST with high p53 protein levels revealed no amplification of the MDM2 gene, suggesting that high p53 levels in MPNST are likely to be due to mutation. The results also indicate that PCNA and Ki67 are potentially useful in distinguishing BPNST from MPNST, particularly in problematic cases of cellular schwannoma versus MPNST. The detection of p53 in a large percentage of cells of a plexiform neurofibroma giving rise to MPNST and Ki67 in 5% and 25% of cells of two similar cases suggests that malignant transformation may be detected in some cases by p53 and proliferation markers prior to overt histological evidence of malignancy.
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PMID:Immunohistochemical and molecular analysis of p53, MDM2, proliferating cell nuclear antigen and Ki67 in benign and malignant peripheral nerve sheath tumours. 755 41

The purpose of this study was to characterize the clinical and histological features of intraoral squamous cell carcinoma in men who were seropositive for the human immunodeficiency virus and to evaluate viral cofactors (human papillomavirus, herpes simplex virus, Epstein-Barr virus), proliferative index (proliferating cell nuclear antigen), a factor associated with invasion (cathepsin D), and mutated tumor suppressor gene and proto-oncogene products (mutated p53, c-erbB-2). Four men who were seropositive for the human immunodeficiency virus and had acquired immunodeficiency syndrome presented with painful oral lesions of variable duration. Oral cancer risk factors included heavy tobacco use (four of four), heavy alcohol use (three of four), and previous radiotherapy (one of four). The lesions consisted of ulcers (two of four), a fungating mass (one of four), and papillary erythroplakia (one of four). Incisional biopsy specimens were obtained. High-stringency in situ hybridization was performed with DNA probes to the human papillomavirus (types 6/11; 16/18; 31/33/35) and Epstein-Barr virus: Immunocytochemical studies for the herpes simplex virus, proliferating cell nuclear antigen, cathepsin D, mutated p53, and c-erbB-2 were performed. Two lesions were moderately differentiated squamous cell carcinoma, one lesion was a basaloid squamous cell carcinoma, and one was carcinoma in situ. Stage of disease at diagnosis was II (one of four), III (two of four), and IV (one of four). Three cases were positive for the human papillomavirus, one case was positive for Epstein-Barr virus, and three cases were positive for the herpes simplex virus. C-erbB-2 was focally positive in one case, and mutated p53 was positive in a separate case.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraoral squamous cell carcinoma in human immunodeficiency virus infection. A clinicopathologic study. 755 63

The human tumour suppressor protein p53 is critical for regulation of the cell cycle on genotoxic insult. When DNA is damaged by radiation, chemicals or viral infection, cells respond rapidly by arresting the cell cycle. A G1 arrest requires the activity of wild-type p53, as it is not observed in cells lacking functionally wild-type protein, and at least some component of S phase and G2/M arrests is also thought to be p53-dependent. p53 functions as a transcription factor which binds specific DNA sequences, and recently major downstream targets have been identified, including p21Cip1, an inhibitor of the cell cycle kinases that also blocks the replicative but not the repair function of DNA polymerase delta auxiliary factor, PCNA. Current interest focuses on developing novel cancer therapies based on our knowledge of the activity of p53 and p21Cip1 in the cell cycle.
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PMID:Tumour suppressors, kinases and clamps: how p53 regulates the cell cycle in response to DNA damage. 757 91

The tumor suppressor protein p53 is intimately involved in the cellular response to DNA damage, controlling cell cycle arrest, apoptosis and the transcriptional induction of DNA damage inducible genes. A transcriptional target of p53, Gadd45, was recently found to bind to PCNA, a component of DNA replication/repair complexes, thereby implicating Gadd45 in DNA metabolism. Using biochemical assays, a role for Gadd45 in excision repair in vitro has been demonstrated. Antisense experiments have also indicated an in vivo role for the GADD45 gene in UV-irradiation survival. These discoveries establish a link between p53 and DNA repair through Gadd45.
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PMID:Stopped for repairs. 757 96

This study was undertaken to determine the extent of apoptosis in lung carcinoma and to evaluate it as a prognostic marker. A series of 75 lung carcinomas (47 squamous cell carcinomas, 24 adenocarcinomas, 3 small cell carcinomas, and 1 large cell carcinoma) was analyzed for the extent of apoptosis by using the 3' end-labeling method of DNA in tissue sections. Apoptosis was correlated with the rate of cell proliferation, the immunohistochemically detectable p53 and bcl-2, the extent of tumor necrosis, and the survival data. The end-labeling method allowed a precise evaluation of the extent of apoptosis. In tumor tissue, the number of apoptotic bodies was roughly 2-fold greater than the number of apoptotic cells, whereas in nonneoplastic control tissues, the ratio was 1:1. The apoptotic indexes (percentages of apoptotic cells and bodies among tumor cells) were slightly higher in adenocarcinoma than in squamous cell carcinoma. There was no association between the extent of apoptosis and the expression of proliferating cell nuclear antigen or p53. On the other hand, tumor necrosis correlated significantly with proliferating cell nuclear antigen and p53 positivity (P = 0.00025 and 0.00087, respectively). Surprisingly, the extent of apoptosis was also found to be independent of the expression of bcl-2. Patients with apoptotic indexes greater than 1.5% had significantly shorter survival time than patients with apoptotic indexes equal to 1.50% or less (P < 0.01 by log rank). Aberrant p53 positivity also predicted a poor prognosis (P < 0.002 by log rank). By multivariate analysis, enhanced apoptosis showed a 1.9-fold risk (P = 0.04), and p53 positivity showed a 2.3-fold risk (P = 0.005) for a shortened survival. We conclude that both enhanced apoptosis and p53 positivity are independent prognostic markers in non-small cell lung carcinoma, predicting shortened survival time of the patients.
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PMID:Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma. 758 40

It is often difficult to predict the outcome of melanoma in patients with Clark level III-IV disease. We sought to identify markers of cell proliferation which may be useful in predicting prognosis. Patients with Clark's level III-IV malignant melanoma who had no local recurrences or metastases were matched with patients of comparable level and thickness who did experience recurrences of metastases. Cell proliferation markers p53, proliferating cell nuclear antigen (PCNA), and Ki-67 were assessed by immunohistochemistry. DNA ploidy was determined by flow cytometry. There was no difference in the expression of p53, PCNA, and Ki-67 between patients with metastases and patients without metastases. However, patients with metastases were more likely to have an aneuploid tumor cell population than were patients without metastases (p < 0.03). Expression of cell proliferation markers do not appear to help predict prognosis in advanced level melanoma; however, aneuploidy may be associated with a greater probability of metastasis.
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PMID:Cell proliferation markers in predicting metastases in malignant melanoma. 759 19

The expression of PCNA and p53 protein was evaluated in a total of 75 cases of benign and malignant lesions of the oral cavity, comprising 50 squamous cell carcinomas (SCCs), 14 leukoplakias, and 11 pleomorphic adenomas. The DNA histogram of 20 SCCs was measured by flow cytometry. p53-positive cells were frequently seen in SCCs, but were rare in leukoplakias and pleomorphic adenomas. The PCNA labeling index (LI) was higher in SCCs than in other benign lesions. The expression rate of p53 protein was markedly elevated in SCCs obtained from smoking patients, when compared to nonsmoking patients. DNA ploidy did not show a close relationship with PCNA and p53 expression. The mean value of PCNA LI for 22 cases carrying positive p53 protein was 52.3%, which was higher than that of p53 protein negative cases (35.7%). The Kaplan-Meier survival curve of the patients who were negative for p53 was significantly more favorable than for patients who were positive for p53 (P < 0.01, Cox-Mantel test). These results suggest that PCNA and p53 LI are markers for the malignant potential of the oral mucosa, and are a useful indicator suggesting a poor prognosis.
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PMID:The significance of PCNA and p53 protein in some oral tumors. 759 56

This study was undertaken in order to investigate the molecular nature of the p53 gene in 19 laryngeal squamous cell carcinomas and dysplasias. Moreover, we have examined the possible relationship between proliferating cell nuclear antigen (PCNA) expression and p53 protein detection status in 42 laryngeal premalignant and malignant lesions in which 14 of the 19 samples used in the molecular study were included. p53 gene analysis was performed with the single-strand conformation polymorphism technique. PCNA was stained with the peroxidase/antiperoxidase immunohistochemical method using the monoclonal antibody PC-10. Data from previous work concerning p53 expression was used. We found that 9 of 12 of the immunohistochemically p53 positive (+) cases had mutations in exons 5 or 6. In the remaining immunohistochemically p53(+) and p53 negative (-) specimens there was no indication of sequence alterations. Furthermore, we did not observe any deletions in the chromosomal region 17p31.1 which encodes exons 4-8 of the p53 gene. The PCNA labelling index (LI) increased progressively with p53 protein detection status (percentage of cells immunohistochemically positive for p53). The difference between the group with the higher percentage of p53(+) cells and the others was statistically significant. These data show that although there is a discrepancy between immunohistochemical demonstration of p53 and molecular analysis, a large proportion of the former harbours the mutant form of the protein. In addition, p53 overexpression is positively correlated with PCNA LI, a finding which accompanies tumour progression.
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PMID:Molecular analysis of p53 gene in laryngeal premalignant and malignant lesions. p53 protein immunohistochemical expression is positively related to proliferating cell nuclear antigen labelling index. 759 85


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