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

Inactivation of DNA mismatch repair genes (MRG) is a recently described pathway of cancer development and progression resulting in genetic instability. Germline mutations in MRG have been studied predominantly in patients with hereditary non-polyposis colorectal cancer (HNPCC) where it is associated with microsatellite instability (MSI). The expression of MRG in primary breast cancer is still largely unexplored. The hMSH2 MRG encodes a protein that recognizes and binds to mismatch sequences of DNA. We investigated the relation-ship between hMSH2 expression and clinicopathological and biological characteristics, including p53 and p185 expression, in 44 primary invasive breast cancers. hMSH2 was not expressed in 11 cases (25%). Interestingly, p53 (p=0.05), p185 and steroidal receptor expression (p=0.07) were more frequent in tumors without hMSH2 expression. Furthermore, in 30 of 44 cases we analyzed hMSH2 expression in relation to MSI at 9 dinucleotide loci, and found that MRG expression was not significantly related to MSI. The presence of hMSH2 and p53 alterations in the same tumor suggests that the two oncoproteins act through a common mutational pathway, whereas the absence of a correlation between hMSH2 and MSI suggests that oncogenetic mechanisms of progression in primary breast cancer differ from those in HNPCC.
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PMID:Loss of hMSH2 expression in primary breast cancer with p53 alterations. 1501 Aug 83

Repair of mismatches in mammalian cell DNA is mediated by a complex of proteins that constitute the so-called mismatch repair system (MMR), the main post-replicative pathway for the correction of replication errors. Loss of MMR (as exemplified by germline mutations in some MMR genes, leading to hereditary non-polyposis colorectal cancer) results in increased mutation rates at both coding sequences and in non-coding regions such as microsatellites. In order to evaluate possible functional alterations of this repair system during ageing that could affect immune system efficiency, we studied microsatellite instability at five different loci interspersed in the genome (CD4, VWA31, Tpox, Fes/FPS and p53) in total DNA from T lymphocyte clones derived from hematopoietic stem cells, or peripheral T cells of young or elderly subjects. In addition, these clones had been maintained for different periods in vitro to represent a culture model of ageing. We observed increasing instability accumulating with increasing passages in culture, particularly in CD34+cell-derived clones, but no clear donor age relationship.
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PMID:Microsatellite instability in in vitro ageing of T lymphocyte clones. 1505 Feb 83

Histological, histochemical and immunohistochemical studies of 50 solitary juvenile polyps (JP) and 50 JP from children with juvenile polyposis syndrome (JPS) were performed. Observations of the focal complex glandular structures with high mitotic rate were more frequent in JP from patients with JPS (n = 29, 58%) than in solitary JP (n = 17, 34%) (p < 0.03). The immunohistochemical study demonstrated p53 overexpression in individual cells and more than 50% of Ki-67-positive cells in 5 (10%) solitary JP and in 17(34%) JP from patients with JPS (p < 0.007). The finding of microglandular pattern is more typical for JP from patients with JPS. Pathological data, expression of p53 and Ki-67 by immunohistochemistry could help to pick out the group of JP with dysplastic changes.
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PMID:[Morphological features of juvenile colon polyps in children]. 1505 6

Recent progresses in molecular biology have allowed us to identify at least two different molecular mechanisms implicated in colorectal carcinogenesis: chromosomal instability and genetic instability. These two molecular mechanisms are supported by two hereditary syndromes that predispose to colorectal cancers: familial adenomatous polyposis and hereditary non polyposis colorectal cancer syndrome. In spite of these two different mechanisms, the signalling pathways implicated the malignant transformation of colonic epithelial cells seem to be the same. They are essentially represented by APC/beta-catenin, TGFbeta, RAS and TP53 signalling pathways. This new molecular classification of colorectal cancers is important for the understanding of molecular alterations responsible for tumour development but also for the management of patients.
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PMID:[Colorectal carcinogenesis: update]. 1508 56

A 49-year-old man presented with a brain tumor and colon carcinoma. The patient had been treated under diagnoses of hereditary non-polyposis colorectal cancer syndrome and Muir-Torre syndrome. Magnetic resonance imaging revealed a mass lesion in the right frontal lobe with diffuse high intensity on T2-weighted and fluid-attenuated inversion recovery images. A few small lesions were enhanced by gadolinium on the T1-weighted images. Histological examination revealed the brain neoplasm was astrocytoma grade III according to the World Health Organization classification. Molecular genetic analysis detected microsatellite instability and p53 mutation only in the tumor tissue, indicating a failure of the deoxyribonucleic acid mismatch repair system. These results suggest that inactivation of mismatch repair system and p53 is closely associated with the tumorigenesis of this neoplasm. The final diagnosis was Turcot syndrome type 1.
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PMID:Molecular analysis of astrocytoma associated with Turcot syndrome type 1--case report. 1509 65

Colorectal cancer (CRC) is one of the most common forms of cancer and the second leading cause of death in Poland. Most cases of CRC are sporadic but a small percentage occurs in heritable syndromes such as dominant autosomal adenomatous and hamartomatous polyposis syndromes and hereditary nonpolyposis colorectal cancers. In a majority of cases CRCs are thought to develop in a step wise progression from normal epithelium through polyp form to carcinoma. Many genetic changes are observed in this process like inactivation of the tumor suppressor genes as well as the activation of specific oncogenes. Molecular biological studies have shown mutations of p53, Apc, k-ras and/or changes in proteins like APC and DNA microsatellite instability or loss of heterozygosity. For several years now great progress in this field and new concepts of screening strategies and therapeutic options have been made (gene therapy).
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PMID:[Genetic aspects of colorectal carcinogenesis]. 1518 54

In order to understand the role of mismatch repair (MMR) gene in colorectal carcinogenesis,microsatellite instability (MSI) status of 16 microsatellite loci of 62 adenomas from 59 patients, including sporadic and familial adeonmatous polyposis (FAP) adenomas were detected by microdissection-PCR-SSLP, and protein expressions of beta-catenin, P53, and BAX, etc. were assayed by immunohistochemistry. Results were as following: (1)The overall MSI alteration rate of the 16 loci was 14.4%. Different adenomas from the same patient showed different microsatellite alterations at the same loci; (2)All of the five FAP patients were MSI-L, three of which showed MSI at the locus of hMSH3; (3)The membrane expression rate of beta-catenin in adenomas and accompanied carcinomas was 42.9% and 11.4%, respectively (P<0.001); (4)Microsatellite alterations of the microsatellite loci of TP53, D5S346, TCF4(A)(9), TGFbetaRII(GT)(3) and TGFbetaRII(A)(10) were associated with the changes of their protein expressions. It could be concluded the following: (1)Microsatellite instability existed even in the early stage (adenomas) of colorectal tumorigenesis. The alterations of chromosome 1p, APC genes, and the TGFbeta signal transduction pathway could also be deduced; (2)In the progression of adenoma to carcinoma, the staining of beta-catenin would be transferred from membrane to cytoplasm and then nucleus, and the cytoplasm stain was stronger in carcinoma than that in adenomas. The abnormality of the signal transduction pathway of APC-beta-catenin-TCF4 could be concluded.
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PMID:[Microsatellite instability and relative gene expressions in sporadic and familial adenomatous polyposis adenomas]. 1562 58

Microsatellite instability (MSI) is associated with defective DNA mismatch repair in various human malignancies. Using a unique fluorescent technique, we have observed two distinct modes of dinucleotide microsatellite alterations in human colorectal cancer. Type A alterations are defined as length changes of < or =6 bp. Type B changes are more drastic and involve modifications of > or =8 bp. We show here that defective mismatch repair is necessary and sufficient for Type A changes. These changes were observed in cell lines and in tumours from mismatch repair gene-knockout mice. No Type B instability was seen in these cells or tumours. In a panel of human colorectal tumours, both Type A MSI and Type B instability were observed. Both types of MSI were associated with hMSH2 or hMLH1 mismatch repair gene alterations. Intriguingly, p53 mutations, which are generally regarded as uncommon in human tumours of the MSI+ phenotype, were frequently associated with Type A instability, whereas none was found in tumours with Type B instability, reflecting the prevailing viewpoint. Inspection of published data reveals that the microsatellite instability that has been observed in various malignancies, including those associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), is predominantly Type B. Our findings indicate that Type B instability is not a simple reflection of a repair defect. We suggest that there are at least two qualitatively distinct modes of dinucleotide MSI in human colorectal cancer, and that different molecular mechanisms may underlie these modes of MSI. The relationship between MSI and defective mismatch repair may be more complex than hitherto suspected.
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PMID:Two modes of microsatellite instability in human cancer: differential connection of defective DNA mismatch repair to dinucleotide repeat instability. 1577 32

Gastric cancer not located in the cardia still remains the second most common cancer worldwide, whereas adenocarcinoma of the cardia and gastroesophageal junction has been rapidly rising over the past two decades. Gastric cancer can be subdivided into two distinct pathologic entities, diffuse and intestinal, that have different epidemiologic and prognostic features. Various genetic and environmental factors play important roles in gastric carcinogenesis; both lead to either abnormal genes overexpression or inappropriate expression of normal genes, whose products confer the malignant phenotype. Advances have been made in the genetic changes mostly of the intestinal type; its development is probably a multistep process, as has been well described in colon cancer pathogenesis, whereas it remains tentative whether the diffuse type of malignancy follows an analogous progression. The most common genetic abnormalities in gastric cancer tend to be loss of heterozygosity of tumor suppressor genes, particularly of p53 or "Adenomatous Polyposis Coli" gene. The latter leads to gastric oncogenesis through changes related to E-cadherin-catenin complex, which plays a critical role in the maintenance of normal tissue architecture. Mutation of any of its components results in loss of cell-cell adhesion, thereby contributing to neoplasia. E-cadherin/CDH1 gene germline mutations have been recognized in families with an inherited predisposition to gastric cancer of the diffuse type. Amplification and/or overexpression of putative trophic factors have also been observed in gastric cancer. Finally, Helicobacter pylori (H. pylori) infection is also involved in gastric carcinogenesis through various mechanisms, thereby necessitating H. pylori eradication in patients with gastric cancer.
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PMID:New concepts of molecular biology on gastric carcinogenesis. 1600 83

We investigated the case of a 13-year-old male with juvenile polyposis (JP) to determine the extent of intraepithelial neoplasia and associated genetic changes, as well as cellular proliferation, within these polyps using immunohistochemistry with antibodies against p53, bcl-2, and Ki-67. Examination of the total proctocolectomy specimen revealed 70 polyps. The 18 largest polyps were investigated microscopically and disclosed the typical hamartomas with frequent erosions of the surface epithelium and reparative changes. Only one polyp showed focal low-grade intraepithelial neoplasia. The immunohistochemical studies revealed an expression of p53 and an abnormal Ki-67 pattern of the surface epithelium only within the neoplastic area. These findings may hint at a possible pathogenetic mechanism for the evolution of colorectal cancer in JP. As in ulcerative colitis, carcinomas in JP may develop along a dysplasia-carcinoma sequence resulting from permanent mechanical insults, inflammation, and repair rather than from an adenoma-carcinoma sequence as in familial adenomatous polyposis (FAP).
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PMID:Juvenile polyposis coli: a facultative precancerosis with some similarities to ulcerative colitis? 1616 47


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