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)

Hypermethylation in the promoter region of the p16 gene was suspected to be involved in the tumorigenesis of colorectal cancers, although its clinical and biological significance remains obscure. In this study, we collected 84 T3N0M0 stage primary colorectal cancers that were curatively resected. The clinicopathologic data were reviewed. p16 hypermethylation was determined by a methylation-specific polymerase chain reaction (PCR). p53 overexpression was detected by immunocytochemistry (ICC). The point mutations in the 12 and 13 codons of the K-ras gene were screened by restriction enzyme analysis. Loss of heterozygosity (LOH) of the DCC (Deleted in Colorectal cancer) gene was examined by PCR using primers of the DCC (18q21) microsatellite marker. The DNA replication error (RER) was examined using 7 microsatellite markers at distinct chromosomal loci. p16 hypermethylation, regarded as an indication of p16 inactivation, was evident in 24 (28.6%) of the tumors. No correlation was found between p16 hypermethylation and various clinicopathologic factors, includinig age, sex, tumor location, tumor size, growth pattern, tumor differentiation, mucin production, vascular and/or lymphatic invasion, lymphocyte infiltration of the tumor, and serum level of carcinoembryonic antigen. There was no association between p16 hypermethylation of K-ras gene mutation, p53 overexpression and LOH of the DCC gene. However, p16 hypermethylation was significantly associated with DNA RER (p = 0.01). Survival analysis revealed a significant survival disadvantage of p16-hypermethylated versus non-p16-hypermethylated tumors (p = 0.0001). These findings indicate that p16 hypermethylation plays a role in the carcinogenesis of a subset of colorectal cancers; and the presence of p16 hypermethylation predicts shorter survival in T3N0M0 stage colorectal cancers.
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PMID:Hypermethylation of the p16 gene in sporadic T3N0M0 stage colorectal cancers: association with DNA replication error and shorter survival. 1046 Oct 63

The purpose of this study was to correlate the presence of p53 antibodies in sera of patients with colorectal adenocarcinoma with size, site and stage of the tumour, age and sex of a patient and the level of carcinoembryonic antigen (CEA) in the serum. p53 antibodies were detected using enzyme-linked immunoabsorbent assay (ELISA). Serum p53 antibodies were detected in 30 of 145 patients (21%), mostly in Astler-Coller stage B1 (28% of patients). No association was found between p53 antibody status in stage A+B1+B2 vs stages C1+C2+D (22% vs 19%) i.e. between patients without and with metastases to regional lymph nodes and/or distant metastases. Serum p53 antibodies were detected in 9 of 34 patients (26%) with tumour localised in the right part vs 21 of 109 patients (19%) with tumours in the left part of the colon and in 18 of 96 (19%) of patients with tumours localised in rectosigmoideum vs 12 of 47 (26%) with tumours in the remaining colon. There was no significant correlation between serum anti p53 antibody and CEA statuses. Increased level of serum CEA was seen in 46/145 (32%) patients. Patients with C1+C2+D stage cancers had high serum CEA level more frequently than did patients with A+B1+B2 stage tumours (44% vs 19% respectively, p < 0.001). Of 102 cases with normal CEA level, 19 (19%) were positive for anti p53 antibodies. These results together with the literature data [11, 20] indicate that approximately 27% CEA negative patients may have serum p53 antibodies. Therefore simultaneous assessment of serum p53 antibodies and CEA seems to be useful for monitoring high risk patients and for postoperative patient monitoring.
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PMID:Clinico-pathological characteristics of colorectal cancer and serum anti-p53 antibodies. 1048 30

The expression of p53 protein was examined in a series of 111 colorectal cancer adenocarcinomas with a long follow-up. A quantitative luminometric immunoassay (LIA) was used for the measurement of wild-type and mutant p53 protein in extracts from colorectal tumour cytosols, p53 being detected in 42% of the samples (range 0.0-52 ng (mg-1)). Using an arbitrary cut-off value of 2.7 ng mg(-1), 25% of the tumours were classified as manifesting high p53 levels. There was no association of p53 expression with patient age, sex, serum preoperative carcinoembryonic antigen (CEA) levels, tumour site and size, nodal status or TNM stage. Significant and independent correlation was found to exist between high p53 levels and prolonged disease-free survival (P = 0.05) at a median follow-up of 60 months. This survival advantage was most apparent among stage III cancer patients. The results from this study would suggest that expression of high p53 levels appear to be useful in selecting a group of colorectal cancer patients with a better prognosis.
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PMID:Expression of high p53 levels in colorectal cancer: a favourable prognostic factor. 1048 22

An autopsy case of a malignant pericardial mesothelioma in a 27-year-old man with no history of exposure to asbestos is reported. He was admitted for heart failure due to pericardial effusion of unknown origin and surgically drained, but later died. The diagnosis of a malignant pericardial mesothelioma was made on the basis of histologic, immunohistochemical and ultrastructural findings. The tumor was located on the pericardium, but autopsy revealed that it had spread extensively in the mediastinum and the lungs. Microscopically, the tumor cells were epithelial like and contained histochemically demonstrable glycogen and hyaluronic acid. Immunohistochemical studies of the tumor demonstrated positive immunoreactivity for cytokeratin 19, muscle actin HHF35, epithelial membrane antigen, CA125, p53 and p21WAF1/CIP1 whereas the tumor was negative for cytokeratins 10 and 17, carcinoembryonic antigen, vimentin, epithelial antigen BerEP4, S-100, c-erbB2 and bcl-2. A high MIB-1 labeling index was noted. Under the electron microscope the tumor cells exhibited long, thin villi. The operation and autopsy findings thus revealed this to be a very rare case of malignant pericardial mesothelioma in a young man.
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PMID:An autopsy case of a malignant pericardial mesothelioma in a Japanese young man. 1050 29

The presence and type of mutations of the p53 tumor suppressor gene were determined in 40 patients undergoing curative hepatic resection for metastatic colorectal carcinoma. This represents the largest series in the literature on the screening of p53 mutations for liver metastases. The analysis was performed in exons 5-9 by denaturing gradient gel electrophoresis followed by direct sequencing. Forty-five percent of tumors showed mutation in p53, and this was observed only in exons 5-8. Mutations at codon positions 167, 196, 204, 213, 245, 281, 282, 286, and 306; deletion of codon 251 and of the first nucleotide of codon 252; and Leu residue (CTC) insertion downstream codon 252 are reported for the first time in colorectal liver metastasis. Mutations at codon positions 163, 248, and 273 have been reported previously. Correlation of p53 status with clinical parameters showed that patients with mutated p53 had a statistically higher number of lesions when compared with patients with wild-type p53 (P<0.050). In particular, of patients with mutated p53, 41% had three or more metastases compared with 14% of patients with wild-type p53. Synchronous metastases were present in 70% of the patients with p53 mutations and in only 29% of patients with wild-type p53 (P<0.025). In addition, patients with p53 mutations are more likely to develop recurrence (73%) compared with patients with wild-type p53 (33%; P<0.001). Other factors considered, including preoperative carcinoembryonic antigen level, bilobar distribution, and size of the lesion(s), did not show significant correlation with p53 status. These results suggest that p53 status might be an important prognostic indicator to predict the pattern and likelihood of treatment failure after hepatic resection.
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PMID:Characterization of p53 mutations in colorectal liver metastases and correlation with clinical parameters. 1058 41

p53 protein overexpression was found to induce the production of antibodies in patient serum and, recently, the easy detection of serum antibodies has been made possible. The aim of this study is to determine the significance of serum p53 antibodies in patients with primary colorectal adenocarcinoma in comparison with their clinicopathological features, and the tumor marker sensitivities of carcinoembryonic antigen (CEA), carcinoma antigen 19-9 (CA19-9) and alpha-fetoprotein (AFP). Thirty-nine of 86 patients (45.3%) were positive for serum p53 antibodies. However, there was no relation with the cancer progression or clinicopathological findings. The sensitivities of CEA, CA19-9 and AFP were 36.0%, 38.4%, and 8.1% respectively, but there was no relation between serum p53 antibodies and these three markers. When the sensitivity of serum p53 antibodies and CEA was evaluated according to clinical stage, the presence of serum p53 antibodies was more significantly associated with stage 0, I and II colorectal cancer than was CEA. Thirty-three patients who showed preoperative positivity for serum p53 antibodies were followed by serial evaluation of circulating antibodies after resection. Negative conversions after resection were significantly higher in the "Cur A" group than in the "Cur B" or "Cur C" groups. Serum p53 antibodies appear to be a useful tumor marker independent of the other markers, especially in the early stage, and are expected to be useful in the development of a method of early diagnosis for mass screening, and as a postoperative monitoring marker for colorectal cancer.
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PMID:[Detection of serum p53 antibodies in colorectal cancer patients and the clinical significance of postoperative monitoring]. 1063 3

Intraductal papilloma is an extremely rare benign salivary gland tumor that occurs most commonly in the minor salivary glands. To our knowledge, a malignant counterpart of intraductal papilloma has not been described previously. We report one case each of benign and malignant intraductal papillary tumors. The benign tumor occurred in the sublingual gland and was a typical example of intraductal papilloma, with the exception that we found no previously published reports of this type of tumor in this location. The other patient had a left parotid gland tumor that was architecturally similar to the intraductal papilloma, with the addition of cytologic atypia, intraductal extension, microinvasion, and lymph node metastases. This tumor was diagnosed as intraductal papillary adenocarcinoma with an invasive component. Both patients were alive and well without evidence of recurrence 2 years and 6 months (case 1) and 6 years (case 2) after surgery. Immunohistochemical examination revealed that the tumor cells resembled duct luminal cells in both cases. The 2 tumors had different immunoreactivities for carcinoembryonic antigen, p53, and Ki-67. The malignant counterpart of intraductal papilloma should be considered in the differential diagnosis of salivary gland tumors with a predominantly papillary structure, even though this tumor is extremely rare.
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PMID:Intraductal papillary tumors of the major salivary glands: case reports of benign and malignant variants. 1065 42

The p53 gene is the most frequently mutated gene in many human cancers, including those of the colon, breast, lung, esophagus, liver and brain. Such genetically mutated tumours are generally associated with progression of the disease and poor clinical outcome. One hundred cases of documented gallbladder carcinomas were reviewed. Twenty-eight cases were randomly selected to evaluate the expression of P53, Bcl-2, carcinoembryonic antigen (CEA) and alpha-fetoprotein, in both the in situ (19 cases) and invasive components (28 cases) of the tumour by the avidin-biotin complex method of immunohistochemistry. These results were correlated with the mean survival intervals in an effort to clarify the progression of the disease and evaluate their role as prognostic markers. Staining to alpha-fetoprotein and Bcl-2 remained consistently negative to weak insignificant staining in both the in situ and invasive components of the tumour in all cases. P53 staining of the invasive part of the tumour was seen in 24 (86%) of the cases and in 17 (89%) of the in situ component. The in situ staining patterns of P53 were not statistically significant in relation to the mean survival. However, in the invasive component, moderate to strong staining tumours, as seen in 15 (54%) cases, were associated with a mean survival of 8.8 months. A similar trend was also observed with staining patterns to CEA. Eighty-nine per cent of the invasive and 84% of the in situ components of the tumour stained positive to CEA. Moderate to strong staining of both the in situ and the invasive components of the tumours was associated with a mean survival of 10.6 months in 76% of cases. This study shows that altered expressions of P53 and CEA are detectable by immunohistochemistry in gallbladder carcinomas. Tumours with increased expression of P53 and CEA of a strong to moderate staining were associated with poor clinical outcomes as evidenced by their mean survival. A stepwise progression of altered CEA and P53 expression may reflect ongoing progression of the disease from the in situ to the invasive phase. However, such trends need to be evaluated in larger numbers and are thus not considered to be true independent prognostic markers.
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PMID:Gallbladder carcinomas: an immunoprognostic evaluation of P53, Bcl-2, CEA and alpha-fetoprotein. 1075 14

Normally, thyroid cancer is a disease with a good prognosis, but about 30% of the tumours dedifferentiate and may finally develop into highly malignant anaplastic thyroid carcinomas with a mean survival time of less than 8 months. Due to the loss of thyroid-specific functions associated with dedifferentiation, these tumours are inaccessible to standard therapeutic procedures such as radioiodide therapy and thyroxine-mediated thyrotrophin suppression. Medullary thyroid carcinomas are also highly aggressive. Here, therapy is limited to surgery, and no alternative is left if patients do not respond to this standard procedure. Obviously, new approaches would be desirable. Several novel approaches are currently being tested for the treatment of thyroid cancer. Many of them utilise methods of gene therapy, but follow different strategies: (1) reintroduction of the tumour suppressor p53 into a background lacking functional p53; (2) suicide gene therapy with ganciclovir and a transduced gene for herpes simplex virus thymidine kinase controlled by the thyroglobulin promoter; (3) strengthening of the antitumour immune response by expression of an adenovirus-delivered interleukin-2 (IL-2) gene; (4) induction of an immune response by DNA vaccination against the tumour marker calcitonin; (5) transduction of the thyroid sodium/iodide transporter gene to make tissues that do not accumulate iodide treatable by radioiodide therapy; (6) blocking of the expression of the oncogene c-myc by antisense oligonucleotides. While these approaches are still tested in vitro or in animal models, first results from pilot studies concerning other novel treatment modalities are available: (7) radioimmunotherapy exploits the carcinoembryonic antigen expressed on medullary thyroid carcinomas to target a radiolabelled antibody to the tumour; and (8) retinoic acid is used for a redifferentiation therapy in the case of thyroid cancer. Hopefully, one or the other of these novel strategies may probably extend after some time the current therapeutic repertoire for thyroid cancers and provide a perspective for otherwise untreatable patients.
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PMID:Innovative strategies for the treatment of thyroid cancer. 1087 26

Specific immunotherapy of cancer utilizes tumor-directed cytotoxic T lymphocytes (CTL) that lyse tumor cells presenting MHC class I-associated peptides derived from tumor-associated proteins. Many tumor-associated gene products are known, but corresponding T cell epitopes are only known for relatively few of these. The most commonly used approaches to identify such antigens require pre-existing CTL lines or clones. By using a CTL-independent high performance liquid chromatography mass spectrometry (HPLC MS)-based approach we identified HLA-A2-presented peptides from carcinoembryonic antigen and wild-type p53 with a copy number as low as eight molecules per cell. Potential epitopes were predicted from the sequences of known tumor antigens and the corresponding synthetic peptides were analyzed by nanocapillary HPLC MS. In parallel, peptides were extracted from fresh, solid tumor tissue or tumor cell lines and analyzed in the same way. Upon co-elution of a natural peptide with a predicted peptide of the same mass, the peptide sequence was confirmed by on-line tandem MS. This approach allows rapid screening of large numbers of tumor-associated gene products for naturally processed peptides presented by different MHC class I molecules as a prerequisite for efficient epitope identification and rapid transfer to therapeutic vaccine trials.
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PMID:Identification of tumor-associated MHC class I ligands by a novel T cell-independent approach. 1094 Sep 13


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