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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of p53 protein in non-neoplastic pleural mesothelium (40 cases) and in human malignant mesothelioma (36 cases) was assessed immunohistochemically using the antibodies DO7, CM-1, and PAb240. In a quarter of the malignant mesotheliomas, there was nuclear immunoreactivity for p53 protein with both the DO7 and CM-1 antibodies. There were no statistically significant differences between the various mesothelioma subtypes (P > 0.05). No immunoreactivity was found with the PAb240 antibody, suggesting absence of mutant-type p53 protein. Nonneoplastic mesothelium was not immunoreactive with any of the antibodies. We conclude that there is immunoreactivity for p53 protein in some mesotheliomas. p53 protein immunoreactivity could be used to discriminate between neoplastic and reactive mesothelium.
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PMID:Immunoreactivity for p53 protein in malignant mesothelioma and non-neoplastic mesothelium. 148 18

The distinction between reactive mesothelium and mesothelioma in pleural biopsy specimens is notoriously difficult, and conventional immunohistochemical markers have provided no relief. The object of this study was to examine the frequency of immunohistochemically detectable p53 overexpression in routinely processed, paraffin-embedded tissue from pleural mesotheliomas and from pleura showing reactive mesothelial hyperplasia, using a polyclonal antibody to formalin-resistant p53 epitopes, and to consider the diagnostic utility of this antibody in the distinction between mesothelioma and reactive mesothelium in pleural biopsy specimens. Immunostaining was enhanced by pepsin predigestion prior to the application of the primary antibody. Positivity occurred in 10/16 epithelial mesotheliomas, 9/19 biphasic mesotheliomas, 2/12 sarcomatous mesotheliomas but in none of 20 reactive pleura. Immunostaining was particularly intense in some of the biopsy specimens, which may be due to the rapidity with which these small pieces of tissue were fixed. In conclusion, this study suggests that p53 immunostaining can help to distinguish epithelial or biphasic mesothelioma from reactive mesothelial hyperplasia in formalin-fixed, paraffin-embedded pleural biopsy specimens.
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PMID:p53 immunostaining in the distinction between benign and malignant mesothelial proliferations using formalin-fixed paraffin sections. 148 19

Twenty cell lines from 17 individuals with malignant mesothelioma have been examined for p53 alterations by direct sequencing of genomic DNA, by evaluation of mRNA expression levels, and by immunocytochemical analysis of p53 protein expression in comparison with normal human pleural mesothelial cells. The results of this study show p53 abnormalities in cell lines from 3 individuals. These include 2 point mutations and one null cell line. Interestingly, while both cell lines with point mutations exhibit high levels of p53 protein, normal mesothelial cells as well as 12 of the mesotheliomas evaluated express low but significant levels. In addition, sequencing of K-ras at codons 12, 13, and 61 reveals wild-type sequence in all 20 mesothelioma cell lines. The capacity to induce tumors in athymic nude mice did not correlate with the presence of a p53 mutation or elevated p53 protein levels. These data suggest that neither p53 alteration nor K-ras activation constitutes a critical step in the development of human mesothelioma.
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PMID:p53 and Kirsten-ras mutations in human mesothelioma cell lines. 156 28

A putative tumor suppressor gene, p53, has been shown to be altered in a variety of human tumor types. The primary mechanism of p53 inactivation is believed to be mutation of one allele followed by loss of the second allele. Malignant mesothelioma is a tumor that has been highly associated with exposure to asbestos fibers, which are known to cause chromosomal abnormalities in mesothelial cells. We have examined four mesothelioma cell lines for genetic abnormalities in p53. Cytogenetic analysis revealed that two of the four tumors had abnormalities (numerical and/or structural) of chromosome 17 (the locus of the p53 gene). Restriction fragment length polymorphism analysis using a chromosome 17p-specific probe (pYNZ22) revealed that two tumors had loss of heterozygosity in the region of 17p13. The relative level of p53 mRNA expression was examined by Northern analysis, with one tumor showing negligible expression of p53 mRNA. The complementary DNA of p53 was generated from the three tumors showing detectable mRNA expression, and the region between codons 70 and 319 was amplified by the polymerase chain reaction and sequenced. DNA single-base substitutions were detected in two of the tumor cell lines, each resulting in amino acid substitutions. One tumor had an arginine to histidine substitution at position 175, and one tumor had a glycine to aspartic acid substitution at position 245. The observed mutations took place in regions of high cross-species sequence homology, indicating that these regions may be functionally important. The correlation of chromosomal loss in 17p on the cytogenetic and molecular level along with p53 mRNA expression and DNA sequence data indicate that genetic alterations in p53 could be a feature of malignant mesotheliomas and may reveal an important role of asbestos fibers in tumor suppressor gene inactivation.
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PMID:Genetic alterations of the p53 gene are a feature of malignant mesotheliomas. 191 60

Abdominal diffuse malignant mesotheliomas develop in rats administered asbestos by the intraperitoneal route. A latency period of 6 to 24 months precedes tumor development; the biological and morphological features of these tumors resemble mesotheliomas in humans. Using one- and two-dimensional gel electrophoresis and immunoblotting, rat mesotheliomas (n = 24) were shown to express two classes of intermediate filament (IF) proteins. The tumors contained both vimentin and at least one of six keratins (p40, Mr 40,000; Dm, Mr 50,000; p53, Mr 53,000; Bm, Mr 53,000; Cm, Mr 54,000; Am, Mr 54,000). Vimentin predominated in 15 of 16 tumors exhibiting either sarcomatous or mixed (epithelial and mesenchymal) appearance. One of eight mixed lesions and six of eight epithelial tumors had a complement of IF proteins in which cytokeratins predominated. A similar pattern has been reported in mesotheliomas in humans (Blobel et al., Am. J. Pathol. 121: 235, 1985). Epithelial tumors often contain comparable amounts of vimentin and low molecular weight cytokeratins, while vimentin is the most actively expressed IF protein in sarcomatous tumors. Thus, tumors induced by asbestos in the rat peritoneum express IF proteins in a manner that resembles human mesotheliomas, supporting the notion that these lesions are appropriate models of human mesothelioma.
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PMID:Intermediate filament proteins in asbestos-induced mesotheliomas of the rat. 244 39

To better understand diseases of the thoracic space, pathologic findings of thoracoscopic open lung biopsy are described based on thoracoscopic anatomy and pleural mesothelioma. A positive colloidal iron stain in the plasma membrane of the mesothelial cells indicates the presence of hyaluronic acid, which appeared to decrease the friction between the lung and thoracic cavity. Excess fluid in the pleural cavity was removed from specific sites in the parietal pleura with stomas. We evaluated the pathologic features of 57 video-thoracoscopic open lung biopsies. Specific diagnoses were established in 89%, and of these half were pneumothorax. Nonspecific pathologic changes were found in 11%, of which interstitial pneumonia was the most common. This procedure is useful in taking a large number of specimens for diagnosis, and to evaluate the degree and progress of fibrosis. The differential diagnosis of mesothelioma from pulmonary adenocarcinoma, reactive mesothelial hyperplasia, and sarcoma of the pleura are described. Also, to understand mutations of the p53 tumor-suppressor gene in mesothelioma, mesothelial lesions were studied with immunostaining for p53 antibody (DO-7) and with in situ hybridization for p53 mRNA. In immunohistochemical staining for DO-7, all reactive mesothelial cells were positive, and 75% of mesotheliomas including epithelial, biphasic, and sarcomatous types were positive, and 75% of mesotheliomas including epithelial, biphasic, and sarcomatous types were positive. mRNA for p53 was expressed in all reactive mesothelial cells, and in 55% of allmesotheliomas.
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PMID:[Thoracoscopic anatomy, significance of pathologic findings in thoracoscopic open lung biopsy, and pleural mesothelioma]. 760 22

The spectrum of p53 mutations differs among human cancer types. We have hypothesized that the p53 mutational spectrum observed in particular tumor types reflects the functional ability of different p53 mutants to modulate wild-type (WT) p53-dependent gene transcription. Missense p53 mutants representing several mutational hotspot codons were cotransfected with WT p53 and analysed for their effects on p53-dependent transactivation of a reporter construct containing a specific p53 binding sequence (PG13-CAT) in human tumor cell lines lacking endogenous p53. Our results show that the ability of p53 mutants to inhibit WT p53-mediated transactivation is cell type dependent. In cell lines derived from a lung adenocarcinoma and a mesothelioma, the transactivation function of WT p53 was strongly inhibited by all p53 mutants examined. However, in cell lines derived from a prostate carcinoma and an osteosarcoma, the mutants examined generally had only minimal dominant negative effects. In cell lines derived from a hepatocellular carcinoma and an ovarian carcinoma, two mutants (248trp and 273his) enhanced WT p53-mediated transactivation of the reporter construct. Additional mutants retained the ability to inhibit WT p53-mediated transactivation in these cell lines. In addition, in a series of four breast tumor cell lines, the p53 mutants examined had similar effects on WT p53 transactivation ability including enhanced transactivation activity in the 273his cotransfectants. The p53 mutants were incapable of transactivating the PG13-CAT reporter in the absence of WT p53 expression. Therefore, the dominant negative effects of p53 mutants on WT p53 function may vary depending on the particular cell type. In addition, mutants with stronger inhibitory capabilities may confer a selective advantage during the tumorigenic process.
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PMID:Effects of p53 mutants on wild-type p53-mediated transactivation are cell type dependent. 778 55

Small cell lung cancer (SCLC) is known to express the HuD protein, the neuronal antigen homologous to Drosophila Elav and Sxl genes involved in neuronal and sex development. HuD is the target of an immune response including high titered antibodies causing paraneoplastic encephalomyelitis and sensory neuropathy. Because the p53 recessive oncogene is mutated and anti-p53 antibodies frequently occur in cancer patients, we wondered if the development of anti-HuD antibodies signaled the presence of HuD mutations in lung cancer. The HuD gene was mapped to chromosome region 1p using a human-mouse hybrid cell panel. We confirmed that 26 of 46 cancer (43 lung cancer and 3 mesothelioma) cell lines expressed HuD mRNA and that this expression, as well as protein expression by Western blot, correlated strongly with the SCLC neuroendocrine phenotype. Southern blot and single-strand conformation polymorphism analyses showed that HuD was not mutated in 78 lung cancers, including patients with the severe paraneoplastic syndrome. Northern blot analysis showed that lung cancer cell lines expressed two major mRNAs (4.3 and 4.0 kilobases) of HuD. We found the three previously described alternative spliced mRNA forms (HuDpro, HuD, and HuDmex). In addition, we also found HuD mRNA had an alternative splicing form in its 5'-coding region. This alternative splice introduced 87 base pairs of sequence and a termination codon resulting in a predicted small, truncated protein (11 amino acids) reminiscent of the male-specific truncated protein in the Sex-lethal (Sxl) gene of Drosophila. However, mRNAs encoding both full-length and truncated proteins were expressed in all SCLCs. These results show that the HuD gene is not mutated in lung cancer, including tumors from patients producing anti-HuD antibodies, but HuD expression is an independent marker or determinant of the neuroendocrine differentiation seen in SCLC.
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PMID:Molecular analysis of the HuD gene encoding a paraneoplastic encephalomyelitis antigen in human lung cancer cell lines. 806 66

Twenty cases of ovarian carcinoma with normal-sized ovaries were examined histologically. Fifteen of them had metastatic disease of the peritoneal cavity and three of the remaining showed uterine involvement. Only in one case was the tumor confined to the ovary, but this patient had experienced systemic chemotherapy before surgery. The remaining case had metastasis of the stomach. Thus, "normal-sized" ovarian carcinoma has a great tendency to spread externally. Histology of the carcinoma was that of common epithelial carcinoma of the ovary with variable degrees of differentiation except for three cases of apparent ovarian metastasis. No cases of definite mesothelioma with ovarian involvement were encountered. A search for determinants of the peritoneal spread was performed using immunohistochemistry for p53 and bcl-2 proteins. However, no differences were found in the antigen expression between the group with and without peritoneal metastasis.
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PMID:Pathological aspects of normal-sized ovarian carcinoma. 875 May 10

Pleural mesothelioma is an asbestos-related malignancy characterized by progressive local growth, late metastases, and median survivals between 8 and 18 months. It is only recently that the in vitro and in vivo characteristics of the malignancy has been investigated. These investigations have been aided by the development of cell lines from patients with the disease, as well as lines developed from asbestos-exposed animals. Nude mouse models constructed with subcutaneous, intraabdominal, or intrathoracic innoculation of cultured cell lines or fresh tumor have been used for evaluating response to innovative therapies. Karyotyping has been performed on a number of cell lines and multiple abnormalities involving many chromosomes have been identified. Aneuploidy is commonly seen, along with reported non-random patterns of chromosomal aberrations. The role of tumor suppressor genes, including p53 is controversial. Multiple growth factors including PDGF are being investigated for a possible paracrine/autocrine loop, and PDGF receptors seem to be differentially expressed in mesothelioma cells compared to normal mesothelial cells. The role of cytokines in the pathophysiology of the disease, secreted either by the tumor cells themselves or by monocyte/macrophages in the local tumor environment, remains to be defined.
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PMID:In vitro and in vivo studies of mesothelioma. 880 96


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