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)

To understand whether p53 gene mutation is an early or late event in esophageal carcinogenesis, biopsy samples of esophageal epithelium from symptom-free subjects in a high incidence area, Huixian county of Henan Province, China, were analyzed. Mutations in exons 5, 6, 7, and 8 of p53 were analyzed by single-strand conformation polymorphism analysis and DNA sequencing. Among the 37 biopsy samples showing accumulation of p53 protein in immunohistochemical staining, missense mutations of p53 gene were detected in 1 of 3 samples with normal epithelia, 3 of 23 samples with basal cell hyperplasia, and 4 of 11 samples with dysplasia. All mutations occurred at exon 5 with 3 at codon 175, 2 at codon 176, and 1 each at codons 159, 135, and codon 132. Of the 8 mutations, there were 3 G to A transitions and 3 G to T transversions. To understand the mutation spectrum and possible causative factors of esophageal cancer in this area, surgically resected human primary esophageal carcinomas from Linxian county were analyzed for p53 gene mutations in exons 5, 6, 7, and 8. Mutations were detected in 16 of 29 samples (55%). Twelve samples contained different missense point mutations, with 75% transitions (7 G to A and 2 A to G) and 25% transversions (2 G to T and 1 G to C). Most of the mutations were located at either exon 5 or exon 7. A deletion and an insertion of nucleotides leading to frame-shift mutations were detected in each of two other samples. The results demonstrate that p53 protein accumulation and gene mutation may occur at very early stages of esophageal carcinogenesis. In carcinomas, there was a higher frequency of p53 gene mutations, which accounts for most of the cases with p53 protein accumulation.
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PMID:p53 tumor suppressor gene mutation in early esophageal precancerous lesions and carcinoma among high-risk populations in Henan, China. 804 81

We analysed p53 protein immunoreactivity in hepatocellular carcinomas (HCCs) and in liver cell dysplasia (LCD) of patients from an area in Northern China, using five anti-p53 protein antibodies recognizing different epitopes of the protein. In HCCs, the overall prevalence of p53 protein immunoreactivity was 78.3%. However, prevalence was strongly influenced by the type of antibody used, ranging from 67.5% for antibody PAb-1801 to only 10.8% for antibodies PAb-421 and DO-7. p53 protein immunoreactivity was not related to type or grade of HCC. In contrast to former reports, p53 protein staining was restricted to nuclei only when using the CM-1 antibody, whereas two other antibodies yielded both, nuclear and cytoplasmic or membrane staining, and no nuclear staining was observed with antibodies PAb-421 and DO-7, the latter two, however, demonstrating cytoplasmic and membrane staining. For LCD, three subtypes were morphologically and karyometrically defined. Nuclei of some LCD cells were p53 immunoreactive, but positivity was restricted to the small cell variant of LCD. Positivity was different for cirrhosis with or without associated HCC, amounting to 18.9% in the former and 39.4% in the latter. Interestingly, p53 protein immunoreactivity also occurred in a set of small hepatocytes not showing the typical feature of LCD and therefore classified as simple regenerating liver cells.
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PMID:Immunohistochemical analysis of p53 protein overexpression in liver cell dysplasia and in hepatocellular carcinoma. 805 55

In general, colorectal carcinoma is thought to originate mainly from adenoma, and this pathway is called the adenoma-carcinoma sequence. Carcinoma in adenoma is an appropriate model for analysis of this mechanism, because adenoma and carcinoma tissues coexist in the same polyp and the carcinoma is thought to have originated from the surrounding adenoma. Expression of the p53 protein was analyzed in 36 cases of carcinoma in adenoma in the colon by immunohistochemistry using an anti-human p53 monoclonal antibody (PAb1801). Alterations of the p53 gene were analyzed by the polymerase chain reaction for microanalysis of normal mucosa, adenoma, and carcinoma from histological slides. Mutations were assessed by the polymerase chain reaction-single strand conformation polymorphism analysis and identified by DNA sequencing in some cases. Loss of heterozygosity was studied by polymerase chain reaction-restriction fragment length polymorphism analysis. Positive staining for p53 was detected in three (8%) of 37 adenomas and 20 (53%) of 38 focal carcinomas. One (7%) of 15 adenomas with mild dysplasia, three (14%) of 22 adenomas with moderate dysplasia, and 16 (42%) of 38 focal carcinomas had a mutation in exon 5 through exon 8 of the p53 gene. As for allelic loss in the p53 gene locus, only one adenoma with moderate dysplasia had loss of heterozygosity, whereas six (40%) of 15 focal carcinomas had loss of heterozygosity. Of those tumors (3 of 37 adenomas and 20 of 38 focal carcinomas) that reacted with PAb1801, 78% (18 of 23) showed genetic alterations. Among 52 tumors which showed negative staining, five tumors had a p53 mutation and four of them were nonsense mutations. Putting all of these results together, 71% (24 of 34) of the cases underwent p53 gene and protein alterations during the conversion from adenoma to focal carcinoma. These data clearly indicate that genetic alterations of p53 are involved mainly in the malignant transformation from adenoma to focal carcinoma in colon carcinogenesis. In addition, some cases show heterogeneity of the p53 gene in carcinoma in adenoma of the colon. There may be other pathways than p53 responsible for malignant change in the colon.
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PMID:A frequent alteration of p53 gene in carcinoma in adenoma of colon. 806 81

The progression from benign adenoma to colorectal cancer is underscored by an accumulation of genetic defects involving the activation of protooncogenes and the inactivation by point mutations and deletions of tumor-suppressor genes. Altered p53 has been one of the most commonly observed of these defects. By using a monoclonal antibody, PAb1801, it was possible to detect the accumulation of an altered p53 protein in standard sections of colon-preserving histopathological criteria. We analyzed biopsies from benign and malignant colorectal tumors fixed in 70% ethanol, and detected cells positive for p53 in 65% of 34 carcinomas and 24% of 84 adenomas, but none in the normal-appearing adjacent mucosa. No correlation was found between degree of differentiation of adenocarcinomas and p53 immunodetection. Abnormal p53 protein expression in adenomas ranged from sparsely stained to focally intensive areas. Overexpression of p53 was detected in more tumors taken from the left side of the colon than from the right side. Adenomas with greater villous content and severe dysplasia had a greater tendency to overexpress mutated p53. Cases of multiple synchronous adenomas showed different patterns of p53 expression but more positivity was found in adenomas from patients with a synchronous adenocarcinoma. Immunodetection of p53 in 11 biopsies from the same tumors alternatively fixed in 70% ethanol or formalin gave comparable results for adenocarcinomas but was not consistent for adenomas. Fifty-four archival formalin-fixed paraffin-embedded colorectal tumors were also stained with PAb1801. p53 was detectable, sometimes with a weaker intensity, in 50% of 18 adenocarcinomas and 22% of 36 adenomas, and most of these showed severe dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunohistochemical analysis of p53 overexpression in human colonic tumors. 807 81

Reports of cases of flat-type colorectal tumors are increasing in Japan, but almost nothing has been elucidated about the genetic abnormalities of these tumors. In this study, we have examined p53 mutations in six cases of colon cancer cell lines, 22 cases of flat-type colorectal tumors, and 27 cases of polypoid-type colorectal tumors using the polymerase chain reaction (PCR) and temperature-gradient gel electrophoresis (TGGE); the latter has recently been developed as a screening method for gene mutations. p53 mutations were observed in four colon cancer cell lines, six flat-type colorectal tumors, and three polypoid-type colorectal tumors, all of which were analyzed by direct sequencing. These mutations were observed only in adenomas with high-grade dysplasia and in colorectal cancers but not in adenomas with low-grade dysplasia. These observations suggest that p53 gene mutations are involved in flat-type as well as polypoid-type colorectal tumors at relatively later stages of carcinogenesis and that TGGE seems to be useful as one of the rapid screening methods.
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PMID:p53 mutations in flat- and polypoid-type colorectal tumors detected by temperature-gradient gel electrophoresis. 808 16

Recent investigations have demonstrated alterations of the p53 tumor-suppressor gene in a considerable number of transitional-cell carcinoma (TCC) specimens. Thus far, these investigations have been restricted to either papillary TCC or invasive bladder cancer. To obtain further information on a possible involvement of p53 in bladder cancer development or tumor progression, investigations of precursor lesions and early stages of this disease are required. Immunohistochemical examination of 6 dysplasias and 24 carcinomas in situ (TIS) showed p53 accumulation, which is suggestive of p53 inactivation, in 2 (33%) and 9 (38%) of these specimens, respectively. This ratio was similar in 9 T1 lesions (33%) and in 14 cases of muscle-infiltrative disease (35%). In papillary tumors, p53 accumulation was observed exclusively in 3/10 moderately differentiated or high-grade lesions but not in 1 Ta G1 tumor. The expression of p53 accumulation was a consistent finding. The examination of tumor recurrences yielded either the presence or the absence of p53 overexpression in the primary and recurrent tumors of 7/8 patients. Similarly, in multifocal TCC, p53 accumulation was also either present or absent in 10/11 cases examined. These results suggest the existence of at least two different subgroups of TCC, with p53 accumulation being present in one of these groups. The observation of p53 accumulation in dysplasia and in TIS is a prerequisite for a possible involvement of p53 in bladder cancer carcinogenesis, although it does not prove this assumption.
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PMID:P53 accumulation in precursor lesions and early stages of bladder cancer. 808 43

The points of this presentation are reform of the theory relating to "Dysplasia and Carcinogenesis" and the cytological methods. In 1976, Meisels and Fortin reported that dysplasia is the disease caused by Human papilloma virus (HPV), and surprisingly, intermediate cells infected by HPV possessed the ability of proliferation and mitosis, resulting in binucleation and multinucleation. In cytology, dysplasia is thought to be delivered from basal cells and abnormal cells are differentiated from lower layer to upper layer, the grade of dysplasia is judged from the level of cell-differentiation. In histology, however, differentiated cells are thought to be normal cells from the histological definition. Therefore, the histological theory cannot explain the fact that the appearance of the abnormal cells from the all layers in cytology of the mild dysplasia. This discrepancy can be understood well if we think it is caused by HPV infection. HPV (ds-DNA) can only proliferate using cellular factors. And as keratinocytes is important with relating to this proliferation, HPV affects human intermediate layer and upper layer. In HPV-infected cells, HPV-E6 protein and E7 protein can bind the products of p53 and pRB, suppressor genes, respectively. These lead to degradation of these proteins' function, acceleration of cell proliferation, and abnormality of cell-cycle time. Our fundamental theory of dyskaryosis is based on these findings. Mild dysplasia is transferred from intermediate layer to upper layer and vanish after cell maturation. Immortalization, transformation, and gene alteration are important factors for carcinogenesis. The deletion of chromosome 3p is one of the most important genetic changes during carcinogenesis. On the basis of carcinogenesis theory described above, the cytological findings of HPV-infected cells are classified into three steps.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Gynecological cytology in theory and practice]. 808 7

p53 gene alterations in ten gastric adenomas and one carcinoma arising in an adenoma were analyzed by deoxynucleotide sequencing. Three (30%) of the ten gastric adenomas had p53 gene mutations, one adenoma showing a frameshift mutation and two others showing silent mutations. In addition, two missense mutations occurred in the carcinoma arising in an adenoma. Histologically, the adenomas containing silent mutations revealed moderate dysplasia. Immunoreactivity to p53 protein was also examined in 61 gastric adenomas, 19 carcinomas arising in adenomas and 48 early well-differentiated adenocarcinomas of the stomach (these included the tumors analyzed by deoxynucleotide sequencing). No staining for p53 was seen in the pure adenomas, but positive immunoreactivity was observed in 27% of the adenocarcinomas and 10.5% of the carcinomas arising in adenomas. These results suggest that p53 gene mutation is an early event in gastric carcinogenesis and missense mutation may play a crucial role in the conversion from adenoma to adenocarcinoma.
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PMID:p53 gene mutations in gastric adenomas. 809 76

It has been postulated that chronic atrophic gastritis, intestinal metaplasia, and dysplasia are precancerous stages of stomach tumorigenesis. We investigated the timing of p53 alterations in these events of gastric tumorigenesis. Each of 12 cases of archived tissue containing precancerous and cancerous lesions were selected for the detection of p53 alterations. Accumulation of p53 protein was detected by immunohistochemistry. Exons 5 to 8 of p53 gene were examined for mutations by polymerase chain reaction-single strand conformation polymorphism and DNA sequencing. p53 immunoreactivity was detected in 60% of the dysplasia cases and in 60% of the cases with carcinomas. p53 gene alterations were found in 37.5% of the metaplasia cases, 58.3% of the dysplasia cases, and 66.7% of the cases with carcinomas. In 71% of the cases, mutations were shown as G:C-->A:T transition. We conclude that mutation of the p53 gene is an early event in stomach tumorigenesis.
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PMID:p53 alteration in gastric precancerous lesions. 812 36

Mutations in the p53 nuclear oncogene are the most frequent genetic abnormalities encountered in human malignancies. Using the polyclonal antibody CM-1, we have examined the expression of the p53 oncoprotein immunohistochemically in archival material of normal, dysplastic, and malignant gastric mucosa. Abnormal expression of this protein was not observed in biopsies of normal gastric tissue (n = 30) but was detected in 22 of the 36 gastric cancers analysed (61 per cent). Nuclear staining was diffuse in 15 of the positive cancer cases, the remaining seven showing a more varied heterogeneous staining pattern. Abnormal p53 protein was not detected in mild (n = 14) or moderate (n = 16) gastric dysplasia but was present in 3 out of 15 severe dysplasia cases. The results suggest that expression of the p53 oncoprotein is a common finding in gastric cancer and occurs as a late event in the malignant transformation process.
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PMID:Expression of p53 protein in normal, dysplastic, and malignant gastric mucosa: an immunohistochemical study. 813 1


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