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)

The frequency and timing of p53 inactivation in ulcerative colitis (UC)-associated tumorigenesis were investigated using immunohistochemistry (IHC) to detect p53 protein overexpression in 56 carcinomas and 40 dysplastic epithelia derived from 58 patients with UC undergoing colectomy for neoplasia. p53 DNA in 25 of the carcinomas also was evaluated by single-strand conformation polymorphism analysis (SSCP) to detect point mutations in exons 5-8 and by loss of heterozygosity analysis to detect allelic deletions. Point mutations were detected in 20 of the 25 carcinomas (80.0%) undergoing both IHC and DNA analysis. One carcinoma contained an allelic deletion but no mutations of the corresponding allele within the region tested. p53 overexpression occurred in 16 (76.2%) of the 21 carcinomas with point mutations and/or allelic deletions but not in any of those with wild type DNA. Of the 56 carcinomas evaluated by IHC, p53 overexpression occurred in 34 carcinomas (60.7%). The proportion of positive tumors was independent of stage, anatomic location, differentiation, and histological subtype. Overexpression was observed in nine of 20 dysplastic masses devoid of and situated remote from carcinoma (45.0%) and correlated positively with increasing grade of dysplasia (P < .025). In contrast, overexpression occurred in 16 of 20 dysplastic epithelia situated adjacent to carcinoma (80.0%) and correlated with overexpression by the corresponding carcinomas but not with the grade of dysplasia present (P = .013). It is concluded that p53 overexpression can be detected by IHC in most, although not all, UC-associated carcinomas with p53 mutations and/or allelic deletions. Based on this method, p53 overexpression occurs frequently in UC-associated carcinomas regardless of stage and pathological characteristics, in noncancerous dysplastic masses with high grade dysplasia, and in dysplasias of all grades situated adjacent to carcinomas. These findings implicate p53 inactivation in the progression from dysplasia to carcinoma in UC and suggest that its occurrence in dysplastic epithelium may be an independent marker of malignant potential.
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PMID:p53 protein expression in ulcerative colitis-associated colorectal dysplasia and carcinoma. 792 12

Barrett's oesophagus has a well-recognized association with oesophageal adenocarcinoma, with phenotypic progression through dysplasia to malignancy. The nuclear phosphoprotein p53 is a putative tumour suppressor with mutations resulting in both loss of negative growth regulatory function and possible gain of oncogene function. Many mutant forms have a prolonged half-life and are demonstrable with immunohistochemical techniques. We examined 62 endoscopic oesophageal biopsies and 36 oesophageal resections for p53 overexpression using the monoclonal antibody DO-7 on paraffin-embedded tissue. The series included 40 cases of Barrett's metaplasia, 13 cases of dysplasia, and 81 cases of adenocarcinoma. None of the cases of metaplasia was p53-positive, compared with 4/13 cases of dysplasia and 52/81 cases of adenocarcinoma. There was no association between the degree of dysplasia and p53 expression, although a trend emerged of increasing p53 expression with higher tumour grade. We conclude that p53 overexpression is frequent in oesophageal adenocarcinoma and may be related to tumour grade. p53 overexpression is not restricted to neoplastic lesions and mutation of this tumour suppressor may occur early in the malignant progression of Barrett's oesophagus.
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PMID:p53 expression in Barrett's oesophagus, dysplasia, and adenocarcinoma using antibody DO-7. 793 42

Mutant tumor-suppressor gene p53 is reported in over 50% of hepatocellular carcinomas (HCC). We studied 60 HCC, 30 with large cell liver cell dysplasia (LCD), suggested to be a preneoplastic change progressing to HCC, in the adjacent non-neoplastic liver. Immunohistochemistry was performed for the presence of mutant p53 and hepatitis B surface (HBs) and core (HBc) antigens, using a labeled streptavidin-biotin technique with monoclonal (1/20) and polyclonal (1/40) anti-p53 and with anti-HBs (prediluted) and anti-HBc (1/400). Twenty-nine (48%) HCC were p53 immunopositive, with both antibodies in 9, 17 with monoclonal p53 only, and 3 with polyclonal p53 only. p53 immunoreactivity was present in 3 of 19 (16%) non-neoplastic livers, 4 of 20 (20%) cirrhotic livers, and one of 30 (3%) LCD. HBs and HBc, respectively, were present in 0% and 5% non-neoplastic livers, 20% and 10% cirrhotic livers, 7% and 10% LCD, and 3% and 5% HCC. None of the p53-positive HCC had HBV markers in adjacent liver. This frequency (48%) of p53 in HCC is similar to that in other countries. The data suggest a role for p53 mutations in hepatocarcinogenesis, even in the absence of HBV infection, apparently not progressing through LCD but occurring as a late event.
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PMID:Immunohistochemical p53 in hepatocellular carcinoma and liver cell dysplasia. 793 18

The tumour suppressor genes Rb and p53 are mutated in several types of human cancer, and many tumour types carry mutations in both genes. To study how these genes normally function, we and others have created mouse strains with Rb and p53 mutations. Here we describe the phenotypic effects of combined germline mutations in these two tumour suppressor genes. Mice mutant for both genes have reduced viability and exhibit novel pathology including pinealoblastomas, islet cell tumours, bronchial epithelial hyperplasia and retinal dysplasia. These data indicate that mutations in Rb and p53 can cooperate in the transformation of certain cell types in the mouse.
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PMID:Cooperative tumorigenic effects of germline mutations in Rb and p53. 795 17

To identify the stage in head and neck carcinogenesis at which p53 abnormalities become important, we evaluated 512 squamous epithelial tissue samples (201 pre-invasive and 209 invasive lesions, as well as 102 normal epithelia) in specimens from two institutions. Of 311 patients evaluated, 128 did not have an invasive carcinoma. The frequency of p53 overexpression in the pre-invasive lesions was not influenced by an adjacent invasive tumor. There was an increasing frequency of p53 overexpression in specimens from histologically normal epithelium (5%, with only scattered basal layers positive) to mild (28%) and moderate dysplasia (47%). p53 overexpression was also significantly more common in lesions with severe dysplasia (54%) and carcinoma in situ (CIS; 50%) than in those with mild dysplasia. To further evaluate the timing of p53 alterations in the development of head and neck cancer, paired epithelial samples (one pre-invasive and one invasive) from the same patient were evaluated. A discordance in the p53 staining pattern was seen in approximately one-third of the cases. When a discordance was present, the frequency with which the invasive lesion was positive but the non-invasive negative decreased from 97% (invasive versus normal epithelium) to 50% (invasive versus severe dysplasia or CIS). When p53 expression was evaluated by site, buccal lesions appeared to overexpress p53 more frequently than tongue lesions. In conclusion, p53 protein overexpression is an early event in head and neck carcinogenesis and may represent a biomarker for patients with pre-invasive lesions.
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PMID:p53 is overexpressed in fifty percent of pre-invasive lesions of head and neck epithelium. 795 65

Mutations in oncogenes and tumour suppressor genes may have an important oncogenic role. Although flat type tumours have been frequently detected in recent years, ras and p53 expressions have not been studied in these tumours. Using a monoclonal and polyclonal antibody to the ras p21 and p53 product, paraffin wax embedded sections of 98 colorectal tumours (43 cases of the flat type colorectal tumour and 55 cases of polypoid type tumour) were stained using the immunoperoxidase technique. Staining was evaluated by light microscopic examination. Positive staining rate of ras p21 for the flat type was 0%; for the polypoid type, it was 60% in cancer with submucosal invasion, 82% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The positive staining rate of p53 for the flat type was 50% in submucosal cancer, 9% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. For the polypoid type, it was 40% in submucosal cancer, 12% in adenoma with high grade dysplasia, and 0% in adenoma with low grade dysplasia. The intermediate staining rate of p53 in the polypoid type was 20% in submucosal cancer and 41% in adenoma with high grade dysplasia. It was seen that p53 was commonly expressed in both flat and polypoid lesions, p21 was not expressed in flat lesions, whereas it was commonly expressed in polypoid neoplasms. In the flat type cancer, a genetic change different from that of the polypoid type cancer is suggested.
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PMID:Comparative clinicopathological and immunohistochemical study of ras and p53 in flat and polypoid type colorectal tumours. 795 33

The objective of this study was to quantify the changes in p53 and cyclin D1 protein levels in different stages of human esophageal and gastric cardia carcinogenesis in a high-risk population in Henan, China. Immunoreactivity of p53, cyclin D1 and proliferating-cell nuclear antigen (PCNA) was observed in the cell nuclei of esophageal and gastric cardia biopsies. The number of p53-immunostaining-positive cells was low in normal epithelia, slightly increased in basal-cell hyperplasia (BCH), markedly increased in dysplasia (DYS) (10-fold), and further increased in squamous-cell carcinoma (SCC) (40-fold). This pattern of change was similar to that of cell proliferation as indicated by PCNA immunostaining. On the other hand, the number of cyclin D1-immunostaining-positive cells did not increase from BCH to DYS, although a slight increase from DYS to SCC was noted. In the gastric cardia, again, the pattern of change of p53-positive cells in different stages of lesions paralleled the pattern of cell proliferation. The number of p53-positive cells was very low, much lower than that of PCNA-positive cells, in normal, chronic superficial gastritis (CSG) and chronic atrophic gastritis (CAG); therefore, the increase of p53-positive cells from CAG to DYS was more dramatic (100-fold). From DYS to adenocarcinoma (AC), the p53-positive and the PCNA-positive cells increased 4-fold. On the other hand, the number of cyclin D1-positive cells did not increase in pre-cancerous lesions, but increased slightly in AC. This study demonstrates that p53 protein accumulation increased with the progression of pre-cancerous lesions, especially in the genesis of dysplasia, both in the esophagus and in the gastric cardia. Our approach of quantitative immunohistochemistry sheds light on the mechanisms of genesis of esophageal and gastric-cardia cancers, which frequently occur together in many high-incidence areas.
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PMID:Changes in p53 and cyclin D1 protein levels and cell proliferation in different stages of human esophageal and gastric-cardia carcinogenesis. 796 Feb 22

Barrett's esophagus is a metaplastic condition with an unpredictable potential for neoplasia. Mutations of the tumor-suppressor gene p53 have been implicated in the evolution of some carcinomas. These mutations frequently result in intranuclear protein accumulation, which can be detected immunohistochemically. This study was undertaken to determine whether p53 immunoreactivity in Barrett's esophagus is a marker of neoplasia and, if so, when it occurs in the metaplasia-dysplasia-carcinoma sequence. Twenty-eight esophageal resection specimens were studied. Barrett's mucosa was present in each specimen, low-grade dysplasia in 27, high-grade dysplasia in 26, intramucosal cancer in 18, and submucosal cancer in 5. Immunohistochemical staining with the monoclonal antibody Pab1801 was used to detect the intranuclear protein product of mutated p53. No p53 immunoreactivity was seen in specimens of Barrett's mucosa or low-grade dysplasia. p53 immunoreactivity was found only in specimens of high-grade dysplasia, intramucosal cancer, and submucosal cancer. Sixty-nine percent (18/26) of these specimens exhibited mutated p53; 18 of 26 specimens of high-grade dysplasia (69%), 12 of 18 intramucosal cancer specimens (67%), and two of five submucosal cancer specimens (40%) expressed mutated p53. When p53 staining was observed, the spectrum of neoplastic changes (high-grade dysplasia, intramucosal cancer, submucosal cancer) within the specimen was positive. We conclude that (1) p53 immunoreactivity in Barrett's esophagus is a frequent, but not inclusive, marker for high-grade dysplasia, intramucosal cancer, and submucosal cancer and (2) immunoreactivity occurs late in the metaplasia-dysplasia-carcinoma sequence, during the transition to high-grade dysplasia.
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PMID:p53 immunoreactivity in Barrett's metaplasia, dysplasia, and carcinoma. 798 83

Adenocarcinoma arising in Barrett's oesophagus is often preceded by mucosal dysplasia, but little is currently known about the aetiology or natural history of this dysplasia/carcinoma sequence. To investigate the participation of the tumour suppressor gene p53 in this sequence, an immunohistochemical analysis of p53 protein overexpression, which is known to closely correlate with point mutation of the p53 gene, was conducted in 30 patients with Barrett's adenocarcinoma. Adjacent Barrett's mucosa was dysplastic in 21 (70%) patients. Sixteen (53%) tumours overexpressed p53, 10 of which had adjacent dysplastic Barrett's mucosa. In all 10 patients, this dysplastic mucosa also overexpressed p53, predominantly in areas of high grade compared with low grade dysplasia. In contrast, none of the dysplastic mucosa adjacent to 11 tumours lacking p53 overexpression showed detectable values of p53. These results suggest that p53 dysfunction may participate in the progression from dysplasia to carcinoma in some patients with Barrett's oesophagus.
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PMID:Adenocarcinoma arising in Barrett's oesophagus: evidence for the participation of p53 dysfunction in the dysplasia/carcinoma sequence. 802 Aug 1

The four principal gut epithelial cell lineages undergo continuous and rapid renewal during a geographically well-organized migration along the crypt-to-villus axis. The molecules that regulate their proliferation and differentiation programs are largely unknown. The large tumor antigen (TAg) of wild-type (wt) simian virus 40 (SV40) and its mutant derivatives represent tools for describing the contributions of regulators of the cell cycle to the proliferative state of each lineage. Expression of SV40 TAgwt in postmitotic, villus-associated enterocytes of transgenic mice causes them to reenter the cell cycle without an apparent effect on their state of differentiation. When human KRAS with a Val-12 substitution ([Val12]KRAS) is coexpressed with SV40 TAgwt in villus enterocytes of bitransgenic animals, the two oncoproteins cooperate to produce dedifferentiation (dysplasia). SV40 mutant d11137 expresses a TAg that is unable to complex with p53 but retains N-terminal transforming functions, including the ability to complex pRB, p107, and p300. When SV40 TAgd11137 is expressed in villus enterocytes, they reenter into the cell cycle. However, coexpression of SV40 TAgd11137 and [Val12]KRAS does not produce dysplastic changes. Thus, the N-terminal 121 residues of TAg are sufficient to perturb the proliferative state of the enterocyte but not to produce detectable changes in the state of differentiation when coexpressed with [Val12]KRAS.
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PMID:Expression of wild-type and mutant simian virus 40 large tumor antigens in villus-associated enterocytes of transgenic mice. 804 20


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