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)

Formaldehyde induces squamous cell carcinomas in the nasal passages of rats following chronic inhalation exposure at concentrations of > or = 10 ppm. We have examined the complementary DNA of the tumor suppressor gene p53 from 11 primary formaldehyde-induced tumors for mutation using DNA sequence analysis. A polymerase chain reaction-amplified fragment of the rat p53 complementary DNA containing the evolutionarily conserved regions II-V was directly sequenced from each tumor. Point mutations in the p53 complementary DNA sequence were found in 5 of 11 of the tumors analyzed. These data demonstrate p53 point mutations in formaldehyde-induced squamous cell carcinomas and indicate a common alteration in certain rat and human squamous cell carcinomas of the respiratory tract.
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PMID:p53 mutations in formaldehyde-induced nasal squamous cell carcinomas in rats. 139 39

We have analyzed the expression of the p53 tumor suppressor gene in paraffin-embedded sections of normal and malignant head and neck and lung tumors by immunohistochemistry using the PAb 1801 monoclonal antibody (MAb). The PAb 1801 does not consistently detect its p53 epitope in tissue fixed in 10% buffered formaldehyde. However, the antibody is effective in AMeX-fixed specimens, thereby permitting the improved morphologic localization of p53 phosphoprotein in paraffin embedded tissue. Of 33 primary head and neck carcinomas analyzed from AMeX-fixed, paraffin-embedded sections, 21 (64%) showed heterogeneous staining with PAb 1801. All 33 normal samples of head and neck tissues were negative. Similarly, 13 out of 20 lung carcinomas (65%) showed heterogeneous staining while none of normal lung tissues were positive. The data indicate a strong positive correlation between p53 detection by PAb 1801 and carcinomas of the head and neck and of lung. However, there was no obvious correlation between p53 staining and the number of involved nodes, the stage of disease or the degree of differentiation in these carcinomas.
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PMID:Improved immunohistochemical detection of p53 protein in paraffin--embedded tissues reveals elevated levels in most head and neck and lung carcinomas: correlation with clinicopathological parameters. 144 95

Mutation of the p53 tumor suppressor gene is a common event in many human cancers and has been specifically associated with invasive squamous cell carcinoma of the human skin and respiratory tract. Alterations in the p53 gene have also been identified in certain rodent tumors, including formaldehyde-induced nasal squamous cell carcinomas. Overexpression of transforming growth factor-alpha (TGF-alpha) is associated with carcinomas of the head and neck and respiratory tract in human patients and formaldehyde-induced rat nasal squamous cell carcinomas. Sections of rat noses containing tumors and other formaldehyde-induced lesions from rats exposed to 15 ppm formaldehyde vapor were examined using immunohistochemical techniques to detect and identify potential relationships between the presence and distribution of p53, proliferating cell nuclear antigen (PCNA), and TGF-alpha proteins. The five tumors that had p53 mutations were for mutant p53 protein by immunohistochemistry and three of six tumors with no detected p53 mutations were also immunoreactive for p53 protein. The presence, pattern, and distribution of p53 staining in tissue sections depended on the morphology of the lesion. PCNA immunoreactivity was strikingly similar in pattern and distribution to p53 immunoreactivity. The pattern and distribution of immunoreactivity for TGF-alpha did not directly correlate with the other markers. Mutation of the p53 tumor suppressor gene may be an important step in the progression of formaldehyde-induced nasal carcinogenesis in the rat. This study demonstrated that immunohistochemistry is a useful tool for the identification of sites within tumors that might have p53 mutations.
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PMID:Immunohistochemical localization of p53, PCNA, and TGF-alpha proteins in formaldehyde-induced rat nasal squamous cell carcinomas. 774 82

This article summarizes the most recent developments and current practice of immunohistochemistry in the diagnosis of hematologic malignancy. Increased availability of monoclonal antibodies applicable in formaldehyde-fixed and paraffin-embedded tissue is discussed as are immunohistochemical definitions for many small cell lymphoma entities. Evaluation is made of the biologic potential of lymphomas and leukemias by the use of antibodies to proliferation antigens, such as Ki-67 and products of tumor suppressor genes (p53).
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PMID:Immunohistochemical evaluation of hematologic malignancies. 796 Dec 86

Cell lines derived from formaldehyde-induced nasal tumors in Fischer 344 rats were established. All of the lines were found to be epithelial and aneuploid and to express keratin, transforming growth factor-alpha, and epidermal growth factor receptor transcripts. Two of four lines were tumorigenic upon injection into nude mice, and these lines also contained point mutations in the p53 suppressor gene. The data indicate that these lines possess characteristics that make them a valuable tool for the study of chemically induced respiratory tract carcinogenesis.
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PMID:Characterization of cell lines derived from formaldehyde-induced nasal tumors in rats. 814 52

Striking differences were found between different histological types of breast cancer when 263 invasive breast carcinomas were tested for nuclear p53 accumulation in formaldehyde-fixed paraffin sections. Nuclear p53 accumulation was found in > 10% of tumor cells in 61% of medullary carcinomas (22/36), 37% of grade 3 ductal not otherwise specified carcinomas (32/86), 4% of lobular carcinomas (2/47), and 0% (0/7) of mucinous carcinomas. Strong cytoplasmic p53 staining was noted in 32% of lobular carcinomas. High percentages of medullary and high-grade ductal breast carcinomas accumulate nuclear p53, but these tumors have favorable and poor prognoses, respectively. Thus, whereas nuclear p53 accumulation can be associated in these tumors with high morphological malignancy grades in general and with tumor cell proliferation in particular, p53 accumulation is not necessarily correlated with biological aggressiveness. Overall incidence of p53-positive tumors in a particular series of breast carcinomas (in our study 28%) will depend on the ratio of ductal not otherwise specified, medullary, and lobular carcinomas.
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PMID:Nuclear p53 protein accumulates preferentially in medullary and high-grade ductal but rarely in lobular breast carcinomas. 829 10

In immunohistochemistry, it is well known that the majority of monoclonal antibodies to keratins work best on fresh frozen tissue specimens, yet in clinical practice most biopsies are routinely fixed in formaldehyde. This seriously limits the range of keratins that can be reliably assessed in retrospective studies (particularly where only rare archival material exists) and where subtle changes during tissue differentiation may be important. Antigen retrieval using exposure to microwave radiation is one technique that has been applied successfully to other tumour markers (e.g., p53). However, few papers have used this method when immunolabelling for keratins, in spite of the widespread use of antikeratin antibodies as markers of differentiation. The effect of keratin antigen retrieval using microwave processing was assessed on a range of oral mucosal biopsies, since the oral cavity displays a wide range of keratins. A panel of six well characterized antibodies was chosen: LP34 (Ck1, 5, 6, 18), LH1 (Ck10), LL025 (Ck16), A53 BA2 (Ck19), AE8 (Ck13), and E3 (Ck17). For each specimen, one piece was stored in liquid nitrogen and another piece fixed in formalin. Tissue sections were cut from each and, using the peroxidase avidin biotin technique, keratin expression was recorded for a frozen section, a dewaxed section, and a microwave-heated dewaxed section. Although overall there was a 25% improvement in identification of keratins after microwaving, some antibodies performed better than others. Given that keratins have been shown to be of value in tumour diagnosis, this study suggests that microwave processing of archival material can be a valuable adjunct to such analysis.
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PMID:Keratin antigen retrieval in oral mucosal biopsies using microwave processing. 901 9

We have performed immunohistochemical staining for p53 and c-erbB-2 on formaldehyde-fixed, paraffin-embedded primary invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60 months. All of them had received postoperative chemoradiation therapy. We have analyzed the association of these factors with epidemiologic risk factors, histopathologic features and hormonal receptor status and the influence on prognosis. Our results indicate that the expression of c-erbB-2 protein defines a group of node-negative patients with poor prognosis. The overexpression of c-erbB-2 has shown a significant association with estrogen receptor status (those tumors expressing c-erbB-2 are usually estrogen receptor negative), presence of fibrosis and lymphoplasmacytoid infiltrates. P53 expression has shown no relation either with prognosis or with any other histopathologic or clinical feature. The only factors with prognostic influence in our series have been tumor size, the presence of node metastases, TNM stage and the prognostic morphometric index (Baak's index), apart from c-erbB-2 in node-negative patients. However, only the TNM stage showed an independent association with prognosis after a multivariate analysis. In summary, in our experience the expression of p53 protein has no prognostic influence on breast carcinoma, and TNM stage remains to be as the most powerful prognostic factor in these patients.
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PMID:Immunohistochemical expression of p53 and c-erbB-2 in breast carcinoma: relation with epidemiologic factors, histologic features and prognosis. 922 51

Estimated vascular density obtained with the aid of antibodies against endothelial cells has been claimed to be an independent prognostic indicator for invasive ductal breast carcinoma. Since 1991 most studies have counted the number of vessels with the optic microscope. We have performed immunohistochemical staining for Factor VIII on formaldehyde-fixed, paraffin-embedded primary invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60 months, who had received postoperative chemoradiation therapy. We have performed a manual count with a 20x objective of the vessels in the vascular hot-spot identified in a 4x field. We analysed the association of this factor with epidemiological risk factors, histopathological features, hormonal receptor status and p53 and c-erbB-2 expression and the influence on prognosis. In univariate analysis vascular density is a significant prognostic indicator in both node-negative and node-positive patients, together with staging, Baak's morphometric multiparametric index, tumour size and histological grade. However, in multivariate analysis only tumour staging and vascular density are independent prognostic factors in breast carcinoma.
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PMID:Vascular density as a prognostic indicator for invasive ductal breast carcinoma. 958 76

Downstream target genes of p53 are thought to mediate its tumor-suppressive activity, but it is unknown whether differential transactivation of these genes is regulated at the level of p53 binding to their promoters. To address this issue, p53 binding in vivo to consensus sites in the p21(Waf1), MDM2, and PIG3 promoters was investigated in cells exposed to adriamycin (ADR) or ionizing radiation as well as in an inducible p53 cell line. p53-DNA complexes were cross-linked in vivo by treating the cells with formaldehyde and processed by chromatin immunoprecipitation-PCR. This methodology allowed for the analysis of relevant p53-DNA complexes by preventing redistribution of cellular components upon collection of cell extracts. Increased p53 binding to the p21(Waf1), MDM2, and PIG3 promoters occurred within 2 h after p53 activation; however, significant increases in PIG3 transcription did not occur until 15 h after p53 binding. Gel shift analyses indicated that p53 had lower affinity for the consensus binding site in the PIG3 promoters compared to its consensus sites in the p21 and MDM2 genes, which suggests that additional factors may be required to stabilize the interaction of p53 with the PIG3 promoter. Further, acetylated p53 (Lys382) was found in chemically cross-linked complexes at all promoter sites examined after treatment of cells with ADR. In summary, the kinetics of p53 binding in vivo to target gene regulatory regions does not uniformly correlate with target gene mRNA expression for the p53 target genes examined. Our results suggest that target genes with low-affinity p53 binding sites may require additional events and will have delayed kinetics of induction compared to those with high-affinity binding sites.
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PMID:Kinetics of p53 binding to promoter sites in vivo. 1131 63


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