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 expression of p53 protein was immunohistochemically studied in formalin-fixed paraffin-embedded biopsy specimens of 203 colorectal carcinomas by use of a monoclonal antibody specific for the p53 protein. PAb1801. p53 protein expression with its reactivity localised in nuclei was found in 121 (59.6%) of the cancers. There was no correlation of p53 immunoreactivity with histological classification, wall invasion, lymphatic invasion, venous invasion, lymph node metastases, or peritoneal metastases. p53-positive cancers were more frequently associated with liver metastasis than p53-negative ones. Patients with p53-positive tumours had significantly poorer prognoses than those with p53-negative tumours. The 5 year survival rate was 58.1% for patients with p53-positive tumours, and 76.3% for those with p53-negative tumours. In Dukes' stage C tumours, an especially good correlation was found between p53 immunoreactivity and prognosis. In addition, patients with p53-positive tumours had higher recurrence rates. The results indicate that p53 immunoreactivity may be a useful prognostic marker of colorectal cancers.
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PMID:p53 immunoreaction in endoscopic biopsy specimens of colorectal cancer, and its prognostic significance. 834 96

The current model for colorectal tumorigenesis defines four specific mutations (activation of a ras proto-oncogene and inactivation of the APC, p53 and DCC tumor-suppressor genes) that accumulate in a colonic epithelial cell as it progresses towards a carcinoma. However, further mutations must be needed for progression to malignancy because advanced adenomas have been observed with all four of these mutations. Loss of heterozygosity (LOH) for 11 loci spanning the distal portion of the long arm of chromosome 14 was studied in 89 sporadic colorectal adenocarcinomas and 25 adenomas. The overall rate of LOH in carcinomas was 53% (46/86 informative carcinomas). The smallest region of overlap (SRO) of deletions includes the markers D14S19 to D14S20. No LOH was seen in the 18 informative adenomas examined. There was a significant trend towards higher levels of LOH within the SRO in advanced Dukes' stages (P = 0.016). Since frequent loss of heterozygosity in a specific region of a chromosome may reflect the inactivation of a tumor-suppressor gene located there, these data suggest that a gene involved in the progression of colonic neoplasia may reside on the distal portion of the long arm of chromosome 14, and that its inactivation may be a critical event in this process.
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PMID:Frequent loss of heterozygosity on chromosome 14 occurs in advanced colorectal carcinomas. 843 50

An immunohistological staining for p53 conducted in 114 cases of colorectal cancer. The background risk factors such as pathological and DNA ploidy patterns were analized in all cases. p53 was found in 50.0% (57/114). There was a slight increase in p53 positive cases in the advanced cancers, but it was not statistically significant. Five-year survival rates of Dukes B and C were 42.2% for p53-positive cases and 67.2% for p53-negative cases. There was a statistical difference (p < 0.05), but none in the Dukes A group. Study of p53 in combination with DNA ploidy patterns revealed an even greater disparity in survival rates (p < 0.01) between p53-positive aneuploid cases and p53-negative diploid cases. These results indicate that the staining of p53 in conjunction DNA ploidy patterns may be a useful indicator of prognosis in the cases of colorectal cancer.
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PMID:[Analysis of p53 expression and DNA ploidy pattern in colorectal cancer]. 848 86

Proliferating cell nuclear antigen (PCNA) expression was studied by immunohistochemistry on paraffin-embedded sections of 293 primary colorectal adenocarcinomas and 56 corresponding lymph node metastases. PCNA-positive expression was detected in <25% of tumour cells in 172 (59%) cases and in > 25% in 121 (41%) cases. PCNA accumulation was related to over-expression of c-erbB-2 and p53 and tended to be increased in cases with ras over-expression. PCNA expression was identical in primary and corresponding metastases. No significant relationship was observed between PCNA expression and prognosis and other clinico-pathological variables, including grade of differentiation, growth pattern, Dukes' stage, site, age or sex. We conclude that PCNA expression may be related to alterations of oncoproteins but that PCNA itself could not provide additional information for the development of metastasis and prognosis in colorectal adenocarcinoma.
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PMID:Proliferating cell nuclear antigen (PCNA) in relation to ras, c-erbB-2,p53, clinico-pathological variables and prognosis in colorectal adenocarcinoma. 860 60

To investigate whether genetic changes of the p53 gene and genetic defects in DNA-mismatch repair systems are involved in progression of colorectal carcinomas (CRCs), we examined loss of heterozygosity (LOH) on 17p and mutations in exon 5 through 8 of the p53 gene as well as replication errors (RER) at four microsatellite loci in DNAs from 108 CRCs at all clinical stages (20 Dukes A, 40 Dukes b, 48 Dukes C). We observed that LOH on 17p and/or p53 mutation were detected in 93% of Dukes A carcinomas and in 84% of Dukes C carcinomas, suggesting that the p53 gene is mutated and/or deleted before carcinoma has been produced. RER-positive phenotype was observed in approximately 30% of CRCs, irrespective of clinical stage. These results suggest that genetic instability is likely to play an important role in development of a subpopulation of sporadic CRCs, but not in progression of CRCs. In addition, we found no significant association between genetic alterations and progression of CRCs. We consider that genetic defects in DNA-mismatch repair pathway do not necessarily promote genomic instability at the p53 sequences in CRCs.
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PMID:[Analysis of genetic changes in progression of colorectal cancer]. 867 62

Although intrahepatic infusion therapy with 5-fluorouracil for unresectable colorectal liver metastases may lead to improved overall survival for some patients, it is not clear why a response is not observed in others. Gene alterations in oncogenes or tumor-suppressor genes are critical events in tumor formation, and some of them could play a role in the process of drug resistance. The tumor-suppressor gene p53, which is known to trigger cell arrest or apoptosis in response to DNA damage, is found to be mutated in a wide range of human tumors. The aim of this work is to establish whether a relationship is found between p53 mutations and survival in patients undergoing adjuvant chemotherapy for advanced Dukes' D colorectal cancers. Seventeen tumors from patients treated with 5-fluorouracil regimen via intrahepatic infusion for unresectable colorectal hepatic metastasis were considered. p53 mutations from tumor DNA were detected, after amplification by PCR of exons 5 to 8, by non-radioactive single-strand conformation polymorphism and direct DNA sequencing. Patients with mutated p53 colorectal tumors had short survival, whereas prolonged survival was associated with the presence of wild-type p53 (p = 0.019). Our data suggest that mutated p53 colorectal tumors had a weak response, or even no response, to chemotherapeutic treatment. Routine assessment of p53 status would be helpful in selecting patients with only wild-type p53 gene who have a predictably better response to chemotherapy.
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PMID:p53 mutations as a possible predictor of response to chemotherapy in metastatic colorectal carcinomas. 868 86

Inactivation of the p53 tumour-suppressor gene is common in a wide variety of human neoplasms. In the majority of cases, single point mutations in the protein-encoding sequence of p53 lead to positive immunohistochemistry (IHC) for the p53 protein, and are accompanied by loss of the wild-type allele. Recently, the WAF1/Cip1 gene was identified as one of the genes induced by wild-type p53, and increased expression of p21WAF1/Cip1 has been found to reflect the status of the p53 tumour-suppressor pathway. We investigated the inactivation of p53 in a relatively small, but well-characterised, group of 46 colorectal carcinomas that were previously studied for allelic alterations, ras oncogene mutations and DNA aneuploidy. Alterations in p53 were identified by IHC, loss of 17p and DNA sequence analysis of exons 5-8, whereas p21WAF1/Cip1 protein expression was determined by IHC. p53 mutations were identified in 19 of the 46 tumours (41%), whereas positive IHC for p53 was found in 21 of the 46 tumours (46%). Positive IHC for p21WAF1/Cip1 was detected in 16 of 42 cases (38%). We found no relationship between p21WAF1/Cip1 staining and p53 protein expression or p53 mutational status. Inactivating mutations in the p53 gene correlated with LOH at 17p but not with LOH at 5q or 18q, Dukes' stage, tumour grade or DNA ploidy. There was a higher survival rate independent of Dukes' stage in the group with no alterations in p53 compared with those with evidence of dysfunction of p53, but the difference was not statistically significant. We conclude that inactivation of p53 and altered expression of p21WAF1/Cip1 are common in colorectal carcinoma but do not correlate with each other or with the clinical or pathological parameters investigated.
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PMID:Clinical and pathological associations with p53 tumour-suppressor gene mutations and expression of p21WAF1/Cip1 in colorectal carcinoma. 868 17

bcl-2 was originally identified as an oncogene involved in follicular lymphomas as a result of chromosomal translocation (14;18). It is now believed that bcl-2 is implicated in the regulation of cell death by inhibiting apoptosis and that its expression is not restricted to haematopoietic cells, but is also present in many epithelial and mesenchymal tissues. Recent studies have analysed the expression of this molecule in a variety of non-lymphoid malignancies including lung, breast, prostate, and nasopharyngeal carcinomas and neuroblastoma. In the present study, 50 colorectal adenomas, 10 hyperplastic polyps, and 142 carcinomas, including 25 arising from pre-existing adenomas, were examined using an antibody detecting the bcl-2 protein product. In non-neoplastic mucosa, bcl-2 was expressed in the crypt cells only, whilst the more differentiated surface epithelial cells lacked any demonstrable bcl-2. Forty-one of the 50 adenomas (82 per cent) and 48 of the 142 carcinomas were positive for bcl-2 expression. All hyperplastic polyps were negative. A reciprocal relationship was found between bcl-2 reactivity and p53 overexpression, as detected by DO7 antibody, in approximately 65 per cent of the cases. The bcl-2-positive/p53-negative subgroup showed a strong correlation (P = 0.0056) with negative lymph node status (Dukes' A and B), implying a less aggressive pathway of neoplastic transformation.
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PMID:Early expression of bcl-2 protein in the adenoma-carcinoma sequence of colorectal neoplasia. 869 32

p21 Cip1 was first isolated as one of the cyclin-dependent kinase (Cdk) interacting proteins induced by wild-type p53 gene product, and it appears to play an essential regulatory role in the control of cell proliferation as a potent, tight-binding inhibitor of cyclin-Cdk complex that blocks the G1/S transition of the cell cycle. We have now examined the p21 Cip1 mRNA expression levels in 16 surgically excised human colorectal tumor and non-tumor tissues by Northern-blot analysis with reference to the identification of p53 gene mutations. p53 gene mutations were detected in 6 tumor tissues but not in the other 10 tissues by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) method and following direct sequencing. The mean p21 Cip1 mRNA expression level in tumor tissues was significantly suppressed compared to that of non-tumor tissues, irrespective of p53 gene mutations. In p53 gene mutation-detected cases, the mean expression level of p21 Cip1 mRNAs of tumor tissues was about 60% of that of cases without p53 gene mutation. Moreover, the relative mRNA expression levels of p21 Cip1 significantly decreased as the pathohistological stages progressed by Dukes' staging system, while in patients with liver metastasis these levels were significantly suppressed compared to those of patients without organ metastasis. These results indicate that reduced expression of p21 Cip1 mRNA is critical for growth activity and malignant potential of human colorectal carcinoma, and that the decrease in p21 Cip1 mRNA level is due to p53 gene mutation as well as other mechanisms during human colorectal carcinogenesis.
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PMID:Reduced messenger RNA expression level of p21 CIP1 in human colorectal carcinoma tissues and its association with p53 gene mutation. 879 64

Overexpression of p53 protein was studied in neoplastic specimens of 150 patients registered for colorectal adenocarcinoma in the Health Care District 16 of Modena, Italy, from 1984 to 1986. We selected Dukes' stage B (92) and C (58) patients whose survival and recurrence rates are not easily predictable, with the purpose of defining subgroups of patients at high risk of recurrence. Monoclonal antibody PAb 1801 was used on formalin-fixed, paraffin embedded specimens. Nuclear staining was assessed to divide tumours into three groups: a) negative, b) low expressors, c) high expressors. Histomorphological variables of tumours, major clinical features of the patients and 5-year specific survival, were evaluated and related to p53 status. p53 was found in 71 out of 150 cases (47.3%); 50 tumours were high and 21 low expressors. No correlation was found between p53 overexpression and clinico-pathological variables. No difference in survival was found between patients with p53 positive and negative tumours in the entire series or within Dukes' stage B and C patients. However, the subgroup of patients with stage C rectal cancer seemed to have a better prognosis if the tumour was p53 negative (of borderline significance, p = 0.15). The same results were obtained by grouping low expressor tumours alternatively with negative or high expressors. We conclude that p53 nuclear overexpression does not seem to influence the prognosis of Dukes' stage B or C colorectal cancer patients.
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PMID:Clinico-pathological correlation and prognostic significance of nuclear p53 protein in colorectal cancer. Colorectal Cancer Study Group of the University and Health Care District of Modena. 884 35


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