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)

Cancer chemoprevention is defined as intervention by chemical agents prior to invasion to inhibit or slow the carcinogenic process. Using surrogate endpoint biomarkers in chemoprevention studies may reduce the size, length and cost of clinical prospective randomized trials in high-risk populations. Intermediate biomarkers are measurable alterations in the tissues at risk and include differentiation, genetic composition, biochemical expression, and proliferation. Assessment is possible because invasive epithelial neoplasms are known to begin as intraepithelial proliferations with a spectrum of cellular abnormalities extending to carcinoma in situ. Genetic heterogeneity begins in the intraepithelial phase; a stochastic accumulation of genetic errors characterizes the progression of clonal evolution within the tumor through the process of invasion and metastasis. Pathologic features associated with this process include tumor classification as well as whether it is intraepithelial or invasive. If the process is intraepithelial, the grade and extent of the intraepithelial lesion are reported. If the neoplasm is invasive, tumor size, extent, degree of differentiation (histologic and nuclear grade), mitotic rate, vascular invasion, and lymph node involvement are evaluated. In assessing biomarkers relevant chemoprevention, and without complete regression of the neoplasm with the chemopreventive agent or agents, measurable parameters along with histopathologic features are applicable. Three methods readily applicable for this purpose that can be applied to paraffin-embedded, formalin-fixed tissue include quantitative pathology, immunohistochemistry, and molecular biologic applications. These methods require some consistency in handling and processing the tissues under study; results may deteriorate due to a number of processing variables, including time to fixation, time in fixative, and fixative type. Quantitative pathology, including static image analysis and flow cytometry, can determine total DNA content. Using static image analysis, very small tumors can be studied. In addition, adjacent intraepithelial and invasive components of a tumor may be studied from a single slide. Steroid receptors, oncogenes, and other proteins detectable through immunohistochemical or molecular biologic methods can be quantitated by this technique as well. Cell cycle synthetic function is assayable by both methods. Flow cytometry can calculate the total percentage of cells in S-phase, or the tumor cell S-phase fraction based on the percentage of cells detected between the G0, G1 peak and the G2 + M peak. A similar approach is generally not applicable with current image analysis equipment; however, cell cycle related proteins such as MIB-1 (Ki-67 associated) can be quantified. Immunohistochemical methods can employ a wide variety of monoclonal antibodies to detect oncogene related proteins, including HER-2/neu (c-erbB-2) and p53. Molecular biologic methods, including in situ hybridization, polymerase chain reaction, and in situ PCR, can have many applications when applied to paraffin-embedded tissues, including detection of viral DNA, identification and measurement of apoptosis, and defining gene deletions.
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PMID:Role of the pathologist in biomarker studies. 874 73

The aim of this report was to investigate the expression of the p53 and mdm-2 oncoproteins in astrocytic gliomas and to assess their interrelation to proliferating activities. Using monoclonal antibodies directed against p53 and mdm-2, these proteins were stained immunohistochemically in 60 astrocytic brain tumors with different histologic grade. Positive p53 stained nuclei were detected in 25.4% of the tumor cases. Mdm-2 staining products were only localized in 10.5% of specimens. Significant correlations could be found between p53, MIB-1, PCNA and mitotic index on the one hand, and tumor grade on the other hand. There were no clear relations between mdm-2 expression and proliferation markers. The grade of ploidy has a lower priority for the proliferating activity. In most cases mdm-2 immunoreactivity was strongly associated with a low or negative p53 expression.
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PMID:Immunohistochemically detectable p53 and mdm-2 oncoprotein expression in astrocytic gliomas and their correlation to cell proliferation. 878 Sep 33

Evaluation of the p53 gene protein expression and proliferative potential with MIB-1 monoclonal antibody (MBL Co.), a new marker of cellular proliferation that binds Ki67 in paraffin sections, by immunohistochemical studies were made in 10 cases of the non-recurrent meningiomas and the 8 cases (17 samples) of the recurrent meningiomas. Tissue samples were embedded in paraffin after fixation in 10% formalin, and 3-microns sections were activated by microwave heating before being immersed with p53 protein or MIB-1 monoclonal antibody. The positivity of immunostaining for p53 protein and MIB-1 was calculated as the % values of tumor cell nuclei stained to all tumor cell nuclei examined within several fields under a light microscope. The mean % value of the proliferating cell index (PCI) stained with MIB-1 monoclonal antibody was 2.1% in the non-recurrent meningiomas, and high values of 11.9% were obtained for the recurrent meningiomas. High values of PCI exceeding 3% were indicated in most of the cases of recurrent meningiomas. p53 protein was not found in the 10 cases of non-recurrent meningiomas. However, it was positive showing values of 0.5-8.5% (mean; 3.4%) in 5 of the 8 cases of recurrent meningiomas. 2 of 4 cases of recurrent meningiomas with a benign type of histology at both initial discovery and recurrence revealed p53 protein expression in the tumor tissues. 3 of 4 cases of recurrent meningiomas, which were of the benign type at the initial operation but transformed to the malignant (atypical) type on recurrence, demonstrated positive staining for p53 protein in the tumor tissues. Although positivity for p53 protein was observed in the recurrent meningiomas with high values of PCI with MIB-1, no significant correlation between the values of PCI with MIB-1 and those for the p53 protein expression was found. The p53 gene protein may be altered on tumor recurrence and/or malignant transformation in meningiomas. It is concluded that evaluations of the p53 protein expression and proliferative potential with MIB-1 are important as additional factors for the prediction of tumor recurrence in meningiomas.
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PMID:[P53 protein expression and proliferative potential in non-recurrent and recurrent meningiomas]. 879 5

We studied two cases of ganglioglioma immunohistochemically by MIB-1 and p53 staining. The positive rate of MIB-1 in the ganglionic cells was 5.5% in Case 1 and 7.8% in Case 2, and that of MIB-1 in the gliomatous cells was 1.4 and 6.6% respectively. The labeling index of p53 in the ganglionic cells was 7.3% in Case 1 and 7.7% in Case 2, and that of the gliomatous cells was 1.9 and 3.4% respectively. MIB-1 and p53 did not stain ganglionic precursor cells. These results indicate that the ganglionic cells also take part in proliferation and have potential of malignant transformation.
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PMID:Proliferative potential and malignant transformation of ganglioglioma: immunohistochemical studies by MIB-1 and p53 staining. 886 95

The aim of this study was to examine the immunohistochemical expression of p53 and bcl-2 in Kaposi's sarcoma and relate this with proliferation index (as measured by MIB-1 staining) and clinicopathological subtypes. Twenty formalin-fixed, paraffin-embedded cases of Kaposi's sarcoma were stained with commercially available antibodies to p53, bcl-2 and MIB-1, after pressure cooking antigen retrieval. All cases were strongly positive for bcl-2 with the majority containing more than 75% positive cells. In comparison, p53 expression was less striking. Eleven cases contained less than 24% (+1) of cells staining positively. Only two cases showed greater than 75% of positive cells, and both of these latter two lesions had metastasized. The MIB-1 staining in all cases of Kaposi's sarcoma was strongly positive, irrespective of clinicopathological type, in keeping with the highly proliferative nature of this lesion. Thus, we have demonstrated uniformly increased expression of bcl-2 protein in Kaposi's sarcoma irrespective of clinicopathological subtype and MIB-1 staining, while p53 expression is relatively less common, except in those cases which have metastasized. This may help identify those cases that will behave in a more aggressive manner. However, more cases need to be evaluated to verify this.
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PMID:The immunoexpression of bcl-2 and p53 in Kaposi's sarcoma. 887 50

In this retrospective study we have investigated the expression of Ki-67 and p53 in 175 random cases of cutaneous squamous cell carcinomas by using the monoclonal antibodies MIB-1 and DO-1, respectively. The expression of these antibodies was compared with various histological parameters of prognostic significance. The staining results were also compared with the clinical outcome of the patients. MIB-1 and DO-1 staining showed statistically significant correlation with histopathological grade of the tumor (p < 0.0001 and p = 0.0016, respectively). The degree of immunolabelling of these antibodies also showed significant correlation with tumor depth and tumor thickness (MIB-1 thickness p = 0.02 and depth p = 0.026, and DO-1 thickness p = 0.014 and depth p = 0.005). The majority of the squamous cell carcinomas in our series were Clark's level IV, which therefore did not correlate with the extent of immunoreactivity (MIB-1, p = 0.098; and DO-1, p = 0.885). Mean length of clinical follow-up was 5.2 years. Aggressive tumor behaviour was seen in 17 patients (10.6%) with 6.9% and 3.4% local recurrences and nodal metastasis respectively. A total of 89.4% patients remained disease-free following their definitive surgical treatment. Vulval skin represented the commonest site associated with unfavourable clinical outcome (five of 17 cases). A large number of squamous cell carcinomas in this poor prognosis group showed a high prevalence of immunoreactivity of the antibodies but this did not achieve any statistical significance. We conclude that Ki-67 and p53 expression in cutaneous squamous carcinoma is not an independent predictor of prognosis.
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PMID:Prognostic significance of Ki-67 and p53 immunoreactivity in cutaneous squamous cell carcinomas. 887 97

Due to the low incidence of intramedullary spinal cord tumors there have been few reports considering its proliferative kinetics. In this study, expression of two cell cycle related antigens (PCNA and MIB-1) were immunohistochemically examined by the percentage of positively stained cells were recorded as PCNA and MIB-1 indices. In addition, over-expression of p53 protein was also investigated in 19 cases of intrameduallary spinal cord tumors. In astrocytic tumors and ependymomas, statistically significant correlations were observed between PCNA and MIB-1 indices (R = 0.98). In hemangioblastoma cases, a similar correlation was not observed between PCNA and MIB-1 indices. The MIB-1 indices of hemangioblastoma cases were less than 1.56 while PCNA indices were more than 14.63 despite long-term survival occurred in all cases. The PCNA index in hemangioblastoma was significantly greater (p < 0.01) than all other types of tumors except for glioblastomas. Thus, interpretation of PCNA index must be made with caution in regard to the subgroup of the tumor histology. Over-expression of the p53 protein was observed only in glioblastoma cases. The MIB-1 index appears to be a useful method for predicting the outcome of all cases with intramedullary tumors of the spinal cord.
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PMID:Significance of MIB-1, PCNA indices, and p53 protein over-expression in intramedullary tumors of the spinal cord. 891 30

Wild type p53 protein has been shown by recent investigations to be involved in the negative regulation of cell proliferation, whereas aberrant p53 protein has lost this negative regulation of cell growth. Wild type p53 protein, which has a very short half-life, has generally been considered to be undetectable using immunohistochemical methods; however, according to a recent report, wild type p53 protein may accumulate in the nuclei because of a defective ubiquitin pathway. Aberrant p53 protein has a longer half-life, and thus is visible using immunohistochemical methods. In this study, both the proliferative potential represented by the MIB-1 staining index (SI) and the immunoreactivity of p53 protein in 51 intracranial meningiomas were studied applying immunohistochemical staining methods to archival paraffin sections. The correlation among MIB-1 SI, p53 immunoreactivity, histopathologic findings and the clinical course of the meningiomas was also analyzed retrospectively. Although it is not possible with available reagents to distinguish between aberrant p53 protein and wild type p53 protein, statistical analyses show that p53 protein was immunostained both in meningiomas with high MIB-1 SI and in recurrent meningiomas. This demonstrates the close relationship among p53 immunoreactivity, MIB-1 SI, and recurrence; therefore, the presence of p53 protein by immunohistochemical examination may suggest the proliferative activity of meningioma and is capable of serving as a predictor of future recurrence.
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PMID:Correlation between MIB-1 staining index and the immunoreactivity of p53 protein in recurrent and non-recurrent meningiomas. 898 Mar 54

Consecutive paraffin sections of 105 astrocytomas and 15 oligoastrocytomas were examined for expression of p53, MIB-1 (Ki-67), and proliferating cell nuclear antigen (PCNA). The tumors had been examined previously for genetic abnormalities and by flow cytometry. Regardless of the tumor's stage and grade and the patient's age and gender, p53 expression was found in 40% of tumors. Although p53 expression was associated with a loss on chromosome 17p and was more frequent in aneuploid tumors, it had no association with survival time. The MIB-1 and PCNA labeling indices increased with increasing tumor grade but showed no association with other clinicopathological parameters. In individual tumors, there was poor concordance between any of the variables (MIB-1, PCNA, and p53). Results for p53 and MIB-1 were similar for both astrocytomas and oligoastrocytomas. The MIB-1 and PCNA values appeared to have prognostic utility in univariate analysis but not after adjusting for patient age and tumor grade. The poor concordance between MIB-1 and PCNA in individual tumors indicates that any one means of assessing proliferative potential in gliomas may not be reliable.
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PMID:Analysis of proliferation markers and p53 expression in gliomas of astrocytic origin: relationships and prognostic value. 920 84

We investigated correlations between cell proliferation, p53 overexpression, and degree of malignancy in cutaneous epithelial neoplasms. One hundred and fourteen cases of epithelial neoplasms, including seborrheic keratosis (SEB), basal cell carcinomas (BCCs), solar keratosis (SK), Bowen's disease (BD), and squamous cell carcinomas (SCCs) were examined using argyrophilic nucleolar organizer region (AgNOR) staining. In addition, immunohistochemical analysis using the Ki-67 (MIB-1) and anti-p53 (DO-7) monoclonal antibodies was performed. The ratio of tumorous to normal cells according to AgNOR staining was defined as the AgNOR rate, and the ratio of tumorous to normal cells according to Ki-67 recognition was defined as the Ki-67 rate. SCC lesions showed the highest AgNOR rate among the investigated epithelial neoplasms, followed in order by BD, BCC, SK, and SEB lesions. The Ki-67 rate was highest in BD lesions, followed in order by SK, SCC, BCC, and SEB lesions. Expression of p53 protein was highest in SK lesions. SCC is generally considered to be the most malignant neoplasm, followed in order by BCC, BD, and SK. Thus, our results suggest that the Ki-67 rate and overexpression of p53 protein do not always reflect the degree of malignancy in neoplasms.
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PMID:Cell proliferation and p53 protein expressions in cutaneous epithelial neoplasms. 898 29


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