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)

Two main histological variants of gastric carcinoma have been identified: intestinal and diffuse types. The former is preceded by a sequential chain of events characterized as chronic gastritis, atrophy, intestinal metaplasia, dysplasia, intramucosal carcinoma, and invasive neoplasia. The second type (diffuse) lacks well-recognized precursor changes. Genotypic events in the gastric precancerous process are described, but a clear model of their sequence and relevance is lacking. Cadherins may play a role in determining which type of carcinoma develops. Translocated promoter region-MET rearrangements have been identified since early stages of the process. p53 alterations are reported beginning with the dysplasia stage utilizing immunohistochemical techniques. Single-strand conformation polymorphism and sequencing analysis show alterations in early stages, especially G:C to A:T transitions.
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PMID:Phenotypic and genotypic events in gastric carcinogenesis. 813 16

Barrett's esophagus is considered to be a preneoplastic condition associated with chronic reflux esophagitis. The risk of neoplasia is difficult to assess but appears to be increased by about 40-fold with an incidence of 1:200 patient years. Diagnosis of Barrett's esophagus is made by endoscopy with biopsy of the suspected area. Barrett's is histologically confirmed by the presence of specialized epithelium (intestinal metaplasia). Histologic findings of low-grade dysplasia and high-grade dysplasia have increased neoplastic risks. The development of cancer within a Barrett's esophagus appears to be related to a sequence of molecular events beginning with the loss of the tumor suppressor gene p53 and followed by the loss of the 5q chromosome. Current management of Barrett's esophagus includes controlling reflux esophagitis and following selected patients with surveillance biopsies. Surgical resection has been advocated for patients with high-grade dysplasia, although this has not been proven to be a cost-effective strategy. Prospective management options include long-term omeprazole use, flow cytometry, endosonography, laser-induced fluorescence, photodynamic therapy, and argon laser therapy. However, long-term observation is needed to determine whether these approaches can impact upon cancer development.
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PMID:Barrett's esophagus: current and future management. 813 18

Diagnosis of the neoplastic progression in Barrett's esophagus using the histologic classification of dysplasia is frequently difficult. The tumor suppressor protein p53, when mutated, confers a promoter effect on cell growth. The purpose of this study was to evaluate the applicability of p53 as an intermediate biomarker of malignancy in Barrett's esophagus. Archival analysis of 100 biopsy specimens of Barrett's esophagus and 10 esophageal adenocarcinomas were compared with 35 chronic esophagitis biopsy specimens. Immunocytochemistry using an anti-p53 monoclonal antibody was performed and elevated immunoreactivity quantitated microscopically. Data were analyzed using a logistic regression model. Significant p53 immunoreactivity occurred as follows: chronic esophagitis (0%), Barrett's esophagus without dysplasia (10%), with low-grade dysplasia (60%), with high-grade dysplasia (100%), and adenocarcinoma (70%). All cases of Barrett's esophagus were significantly immunoreactive when compared with the chronic esophagitis cases (p = 0.001). There was an increase in p53 immunoreactivity as the histologic classification progressed toward adenocarcinoma (p = 0.001). Progression to high-grade dysplasia may be predicted based on p53 immunoreactivity. These findings suggest a role for p53 as an intermediate biomarker in Barrett's esophagus.
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PMID:Potential application of p53 as an intermediate biomarker in Barrett's esophagus. 814 27

Large cell liver cell dysplasia (LCD), a suggested preneoplastic change progressing to hepatocellular carcinoma, has been reported associated with alpha-1-antitrypsin deficiency which in some countries has an increased frequency of hepatocellular carcinoma. We examined the nonneoplastic liver from 13 alpha-1-antitrypsin deficiency patients for LCD and, using a labeled streptavidin-biotin technique, for immunohistochemical markers: AAT (1/200), hepatitis B surface (HBsAg, prediluted) and core (HBcAg, 1/400) antigens, and monoclonal (1/20) and polyclonal (1/40) mutant p53, a tumor suppressor gene. There were eight males and five females ranging from 2 mo to 76 yr (mean 40 yr). Nine livers showed cirrhosis, one chronic persistent hepatitis, one portal fibrosis, and two cholestatic hepatitis (in the two infants). The nine cases with LCD included five males and four females of mean age 46 yr (range, 17-71), eight with cirrhosis and one with portal fibrosis. Only one liver with LCD and cirrhosis had HBcAg in cirrhotic and dysplastic cells. No patient had developed hepatocellular carcinoma. All 13 livers were immunonegative for HBsAg and mutant p53, and immunopositive for AAT present in normal, cirrhotic, and dysplastic liver cells. Thus, LCD was identified in 82% of adult alpha-1-antitrypsin deficiency livers (69% including infantile patients), 89% with cirrhosis, and none with malignancy. HB expression was rarely present; serology for HB and/or hepatitis C was positive in 46% adults. Immunoreactive AAT was present in dysplastic cells. p53 gene mutations do not appear to have a role in the pathogenesis of LCD in alpha-1-antitrypsin deficiency.
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PMID:Liver cell dysplasia in alpha-1-antitrypsin deficiency. 815 50

We have analyzed K-ras mutations and p53 alterations in 39 tumor and nontumor samples taken from nine patients with longstanding ulcerative colitis and colorectal carcinoma. Two of nine invasive carcinomas contained a K-ras mutation. By a combination of immunohistochemistry and single-strand conformation polymorphism analysis, p53 alterations were found in three of nine carcinomas. Five of 13 dysplastic lesions harbored a mutated K-ras gene, even in the absence of detectable changes in associated invasive tumors. One single focus of dysplastic mucosa harbored concomitant K-ras and p53 gene alterations. In two patients, a K-ras mutation was detected in epithelial lesions considered to be devoid of malignant potential (villous regeneration, active colitis). Our results indicate that: 1) the prevalence of K-ras and p53 genetic alterations found in ulcerative colitis-associated colonic carcinomas appears to be lower than in sporadic carcinomas; 2) K-ras mutations can be detected in dysplasia, villous regeneration, and active colitis and affect a subpopulation of the cells composing the lesions; 3) diverse genetic alterations can be detected in the same patient and the dysplastic lesions can exhibit a different genotype than the carcinomas; and 4) at least part of active colitis and villous regeneration lesions should be considered as preneoplastic in ulcerative colitis.
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PMID:K-ras mutations and p53 alterations in neoplastic and nonneoplastic lesions associated with longstanding ulcerative colitis. 816 Jul 76

Lung cancer arises after a series of morphological changes, which take several years to progress from normal epithelium to invasive cancer. The morphological changes progress from hyperplasia, to metaplasia, to dysplasia, to carcinoma in situ, to invasive cancer and finally to metastatic cancer. Multiple molecular changes have been documented in lung cancers, both small cell (SCLC) and non-small cell (NSCLC) types. The number of changes has been estimated to be in double digits. How can so many changes develop in one cell? One possible explanation is the "field cancerization" theory, that states that all or much of the aerodigestive tract epithelium has been mutagenized, perhaps as the result of exposure to tobacco products or other carcinogens. The molecular changes include activation of dominant oncogenes (myc family, K-ras and HER/2/neu genes), as well as loss of recessive growth regulatory genes or anti-oncogenes (p53, and rb as well as unidentified gene or genes on chromosome 3). However, cytogenetic and molecular genetic studies indicate that multiple other specific sites of actual or potential DNA loss may be present in lung cancers. Many of the well characterized molecular changes may function as negative prognostic factors for survival in subsets of lung cancers. Other changes may include development of drug resistance, and production of growth factors and their receptors. It is tempting to associate specific molecular changes with specific morphological changes, as has been attempted in the colon. However, because of the difficulties in serially sampling the respiratory tract, only a modest amount of data has been collected to date. It appears that deletions of chromosome 3p, hyperproliferation and aneuploidy are early changes, while p53 mutations appear later in the preneoplastic cascade. Documentation of intermediate markers for lung cancer and prospective studies of their prognostic effects will be necessary for the design of rational chemoprevention trials.
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PMID:The molecular and cellular basis of human lung cancer. 816 65

Immunohistochemically detectable p53 protein using a polyclonal antibody (CM-1) was studied in 42 carcinomas of which 11 were grade I, 22 grade II and nine grade III carcinomas. Additionally 14 urothelial dysplasias were studied. In 11 of these a diagnosis of transitional cell carcinoma was established before and in one after the dysplasia diagnosis. Twenty-one out of 42 (50%) cases of transitional cell carcinoma were positive for the p53 protein. Eleven out of 14 (78%) dysplasias and 10/12 (83%) related carcinomas were p53 positive. One out of 11 grade I (9%), 12/22 grade II (55%) and 8/9 grade III (89%) tumours showed positivity for p53. There were significantly more p53 positive cases in grade II-III tumours than in grade I tumours (P = 0.004). There were significantly more p53 positive cases in stage T2-T4 tumours than in stage T1 tumours (P = 0.035). In only one case among the 11 dysplastic lesions following the treatment of a carcinoma the dysplastic lesion was p53 negative while the preceding carcinoma was p53 positive. All dysplasias and 28 carcinomas were also immunostained for laminin and type IV collagen to evaluate the continuity of basement membranes (BMs). Clearly disrupted BMs were observed only in grade III carcinomas. These cases showed the most p53 immunopositivity. The results show a strong association of p53 staining between dysplasias and transitional cell carcinomas of the urinary bladder indicating that these lesions might share similar p53 changes. The correlation to grade, clinical stage and to disrupted BM suggests that p53 mutations may be associated with the evolution of aggressive growth characteristics in transitional cell carcinomas or, alternatively, that p53 positive tumours of a more aggressive type from the start. Whether p53 staining can be used as an adjunct in the assessment and follow-up of epithelial changes of patients treated for a p53 positive bladder carcinoma deserves to be studied.
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PMID:p53 immunohistochemistry in transitional cell carcinoma and dysplasia of the urinary bladder correlates with disease progression. 821 93

To determine the chronology of p53 mutation in the gastric carcinogenic sequence, we studied p53 overexpression in premalignant lesions, including 17 adenomatous polyps (10/17 surrounded by intestinal metaplasia and 11/17 harboring foci of adenocarcinoma or severe dysplasia), and 18 hyperplastic polyps (4/18 with focal adenomatous changes). Immunohistochemistry with PAb 1801 monoclonal antibody was performed on archival material; p53 nuclear staining was seen in 10/17 adenomas, but was limited to the foci of adenocarcinoma in three cases. Five adenomas with foci of severe dysplasia or carcinoma were nonreactive. Intestinal metaplasia, normal gastric mucosa, and 14/18 hyperplastic polyps were nonreactive. p53 Reactivity observed in four hyperplastic polyps was limited to adenomatous foci. These results suggest that p53 overexpression occurs in dysplastic epithelium of precancerous gastric lesions. Its absence in chronic atrophic gastritis with intestinal metaplasia suggests it is a relatively late event in the gastric carcinogenic sequence.
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PMID:p53 expression in precancerous gastric lesions: an immunohistochemical study of PAb 1801 monoclonal antibody on adenomatous and hyperplastic gastric polyps. 823 42

Some lesions of the oral mucosa such as leukoplakia and erythroplakia may develop into squamous cell carcinoma (SCC). At present, however, there is no method available to predict malignant transformation. It is known that the grade of dysplasia is related to the potential malignant development, but this is unreliable as the only indicator. In 64 hyperplastic lesions and 85 SCC of the oral mucosa, a correlation between the expression of the mutated tumor-suppressor gene p53 and the dysplasia of the lesions was found. Ki 67 was used as a proliferation marker. The results imply that expression of mutated p53 is an indicator for potential malignant development in benign lesions of the oral mucosa.
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PMID:p53 and Ki 67 expression in preneoplastic and neoplastic lesions of the oral mucosa. 824 68

With the goal of identifying a potential intermediate biomarker in the multistep process of head and neck cancer development, we conducted immunohistochemical analyses for p53 expression in 33 patients with head and neck squamous cell carcinomas whose tissue sections contained adjacent normal epithelium, hyperplastic, and/or dysplastic lesions. Fifteen of 33 (45%) squamous cell carcinomas of the head and neck expressed p53, but none of four normal control patients (cancer-free nonsmokers) expressed detectable p53 in oral mucosa specimens. To determine when p53 expression is initiated during head and neck tumorigenesis, we examined the normal and premalignant lesions adjacent to the tumors. Five of 24 (21%) samples of normal epithelium adjacent to tumors, 7 of 24 (29%) samples of hyperplasia, and 9 of 20 (45%) samples of dysplasia expressed p53. Quantitative image analysis demonstrated not only a gradual increase in the amount of p53 expression as tissue abnormalities progressed but also a topological change in expression. Whereas p53 expression, when present, was limited to the basal layer in normal epithelium adjacent to tumor, the expression of p53 expanded into the parabasal and superficial layers in hyperplasia and dysplasia. We conclude that p53 expression can be altered in very early phases of head and neck tumorigenesis. Thus, it may be an excellent candidate for risk assessment and may serve as an intermediate biomarker in chemoprevention trials.
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PMID:Activation of p53 gene expression in premalignant lesions during head and neck tumorigenesis. 827 61


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