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)

Colorectal adenomas are macroscopically visible morphological changes of the mucosa that can develop focal carcinoma in the absence of surgical intervention. The successive molecular changes proposed to occur at different stages in the adenoma-carcinoma sequence were primarily based on DNA studies of exophytic, polypoid-type adenomas. Not all colorectal lesions, however, display an exophytic phenotype and a presumed distinct colorectal neoplasm, the nonpolypoid adenoma, was subsequently described as a precursor of colorectal cancer. The low incidence of KRAS mutations in nonpolypoid colorectal adenomas reported previously suggested a different genetic basis for the transformation process in these lesions. We have pursued the identification of genetic changes in benign sporadic nonpolypoid colorectal adenomas in a selected Swedish patient group with no family history of colorectal cancer. Mutation screening of the adenomatous polyposis coli (APC), KRAS, and TP53 genes was conducted using the protein truncation test, heteroduplex-single-strand conformation polymorphism analysis, and denaturing gradient gel electrophoresis on PCR-amplified fragments. Fourteen mutations in the APC gene were characterized in 10/20 samples. Mutations in the KRAS and TP53 genes were identified in 3/57 and 4/51 adenomas, respectively. The mutation frequencies and distribution of mutations in APC correlate with published data on exophytic adenomas. The low mutation frequency of the TP53 gene is consistent with the benign nature of the research material. KRAS activation (an early event in polypoid colorectal adenomas) apparently does not play a significant role in nonpolypoid adenoma development but may result in the development of a polypoid configuration. Genes Chromosomes Cancer 27:202-208, 2000.
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PMID:Somatic mutations of the APC, KRAS, and TP53 genes in nonpolypoid colorectal adenomas. 1061 10

Mutations in the tumor suppressor gene p53 have been reported as occurring prevalently in a wide range of human tumors. Detection of a mutated p53 is thought to provide useful information for the clinical management of colorectal neoplasm. In this study, we used polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) and sequencing analysis to rapidly screen for mutations in p53 in colorectal cancer in Taiwan. Genomic DNA was purified from colorectal cancer specimens obtained from 80 patients at a teaching hospital in southern Taiwan. Primer sets were designed to amplify fragments within exons 4-8 of p53. We found p53 mutations in 38 of 80 patients. This is the first identification of a mutation at codon 143 of p53 in colorectal cancer in Taiwan. In addition, we found two insertions in exon 5 of p53. The p53 mutation rate among colorectal tumors in Taiwan, found in this study, is 43%. The results indicate that p53 mutation is not significantly associated with tumor grade, age, or gender (p > 0.05). We found that two-fifths of colorectal cancer patients in Taiwan have a p53 mutation, which could be used as a marker of colorectal cancer.
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PMID:Mutations in the p53 tumor suppressor gene in colorectal cancer in Taiwan. 1279 43

It is unclear how expression of the FHIT (fragile histidine triad) gene by the colorectal neoplasm correlates with histogenesis and progression of the disease. We studied the association between expression of Fhit protein and development of colorectal carcinoma (CRC). We also examined relations between Fhit protein expression, macroscopic type, Ki-67 labeling index (LI), and p53 overexpression in carcinoma in situ. We examined 27 colorectal adenomas, 82 carcinomas in situ and 21 invasive CRCs resected endoscopically or surgically. The carcinomas in situ comprised three macroscopic types: polypoid (n=27), superficial (flat elevated, n=27; depressed, n=10) and granulonodular laterally spreading tumor (G-LST, n=23). Fhit, Ki-67, and p53 overexpression were examined immunohistochemically. Levels of Fhit protein were lower in invasive CRC than in adenoma and carcinoma in situ (p<0.01). In carcinoma in situ, reduced Fhit expression was observed in 7 of 22 (31.8%) polypoid types, 13 of 27 (48.1%) superficial flat elevated types, 8 of 10 (80%) superficial depressed types and 7 of 23 (30.4%) G-LST. Frequencies of reduced Fhit expression were significantly higher in the polypoid type and G-LST lesions than in the depressed type (p<0.05). Reduced expression of Fhit protein was related significantly to Ki-67 LI and p53 overexpression in carcinoma in situ (p<0.01). The present findings suggest that reduced expression of Fhit protein is related to development of colorectal neoplasm. Polypoid CRC and G-LST appear to differ from superficial depressed CRC in terms of Fhit expression.
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PMID:Clinical significance of Fhit expression in development of colorectal carcinoma of various macroscopic types. 1296 15

During tumor progression, the accumulation in genetic alterations is a fundamental characteristic of malignant cells. p53 gene is frequently mutated in human tumor. Cellular accumulation of p53 protein can initiate an immune response with generation of circulating anti-p53 antibodies. Patients with ulcerative colitis have an increased risk of developing colorectal neoplasm and, among the different genes involved in carcinogenesis, p53 may play a key role. Sera and tissues from 97 patients (M = 53, F = 44) affected with ulcerative colitis (UC) were collected. Serum anti-p53 antibodies (p53Abs) were detected in duplicate with ELISA method. Serum p53Abs were detectable in 9.3% (9/97) of patients affected with UC. In these patients, the titer of p53Ab ranged between 3.1 and 14.9 U/mL (mean, 6.6 U/mL; SD, 4.64). Serum p53Abs were undetectable in control group. With an immunoluminometric assay for the quantitative determination of p53, we found 9/97 positive samples (> or = 0.69 mg/mg of total proteins). In contrast, the samples of the remaining 89 patients were found negative (< or = 0.30 mg/mg of total proteins). All patients that were positive for anti-p53 antibodies were also positive with p53 protein accumulation in the tissue of colonic biopsies. In UC, follow-up with colonoscopy has several advantages. The colonoscopy is not well accepted by patients, and poor patient observance has the potential to seriously devalue the technique as a screening tool, despite practical considerations of competence within endoscopy service. Serological detection of p53Abs by enzyme-linked immunosorbent assay (ELISA) is easy to perform, does not require tumor specimen, can be performed in a routine diagnostic procedure, may be used in clinical practice, and could facilitate physicians in patient monitoring. We suggest that serum p53Abs assessment, indirect marker for p53 gene mutations, and abnormally high p53 protein levels could be considered to have a potential for use as a complementary test to improve surveillance program performance.
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PMID:Serum p53 antibodies in patients affected with ulcerative colitis. 1547 22

There are two opposing theories of the natural history of colorectal neoplasm, adenoma-carcinoma sequence and de novo carcinogenesis. To elucidate the histogenesis of colorectal carcinoma, we investigated the expression of CD10, MUC2, MUC5AC, MUC6, and p53 in colorectal neoplasms. Sixty-seven morphologically distinct neoplastic specimens were divided into the following groups according to morphology: adenoma (groups A and B), protruded-type carcinoma (group C), superficial-type carcinoma with adenomatous component (group D), or superficial-type carcinomas without any adenomatous component (group E). Diagnoses of adenomas and carcinomas were based upon the Vienna classification of gastrointestinal epithelial neoplasia. The expression of CD10 in group E lesions was more intense than in the other groups. Regardless of morphology, MUC2 expression was significantly decreased in CD10-positive carcinomas, and the p53-positive rate was much higher in CD10-positive than in CD10-negative carcinomas. The overexpression of CD10 and reduced expression of MUC2 may be associated with the development and progression of colorectal carcinoma. A specific tendency was evident in superficial-type carcinomas without any adenomatous component (de novo carcinomas). These carcinomas are considered to be more aggressive than other morphologically distinct carcinomas.
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PMID:Overexpression of CD10 and reduced MUC2 expression correlate with the development and progression of colorectal neoplasms. 1590 Nov 28