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)

Carcinomas of the upper digestive tract (squamous-cell carcinoma of the esophagus, adenocarcinoma of the cardia) from 24 patients residing in Linxian (China) and near-by high-incidence areas were analyzed for mutations in exons 5-8 of the p53 tumor-suppressor gene. Mutations were identified by polymerase chain reaction amplification and direct sequencing in 50% of the specimens. Eleven tumors harbored a single base-pair substitution leading to either an amino-acid substitution (8 tumors) or a chain-termination signal (3 tumors), and one tumor revealed a 15-bp deletion in exon 7 with a silent base substitution adjacent to the deletion site. Mutations occurred in all 4 exons examined, with a preponderance in exon 5. Of the 6 mutations identified among the 14 adenocarcinomas examined, 3 were G to T transversions, a mutation that has thus far been absent from reported mutations in Barrett's esophageal adenocarcinomas and dysplasias from patients residing in Europe and North America.
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PMID:p53 mutations in esophageal tumors from high-incidence areas of China. 776 32

We examined the immunohistochemical expression of proliferating-cell nuclear antigen (PCNA) and p53 proteins in dysplasia and intramucosal carcinoma of the esophagus. Immunohistochemistry was performed with monoclonal antibodies directed against PCNA and p53. We used surgically resected specimens from 29 patients who had a total of 55 lesions of severe dysplasia (n = 16), intraepithelial carcinoma (n = 21), and mucosal carcinoma (n = 18). The mean PCNA index with immunoreactivity for p53 was 48.9 +/- 6.5 in areas of severe dysplasia (n = 7), 58.2 +/- 7.3 in areas of intraepithelial carcinoma (n = 10), and 71.4 +/- 9.3 in the invasive areas of mucosal carcinoma (n = 10). The mean PCNA index without immunoreactivity for p53 was 41.2 +/- 5.5 in areas of severe dysplasia (n = 9), 48.0 +/- 7.4 in areas of intraepithelial carcinoma (n = 11), and 63.7 +/- 9.1 in invasive areas of mucosal carcinoma (n = 8). The PCNA indices of the areas of severe dysplasia with immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma with immunoreactivity for p53. Similarly, the PCNA indices of severe dysplasia without immunoreactivity for p53 were significantly lower than those of intraepithelial carcinoma and mucosal carcinoma without immunoreactivity for p53. These results thus suggest that severe dysplasia has a lower proliferative potential than carcinoma and may therefore represent a precancerous lesion.
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PMID:Expression of PCNA and p53 in esophageal dysplasia and esophageal carcinoma. 930 59

Human papillomaviruses have been widely implicated as important etiologic agents in various squamous cell carcinomas including oesophageal carcinoma. p53 mutant oncoprotein has also been implicated in various tumours. Immunohistochemical analysis was employed to detect the co-expression of HPV and p53 mutant protein in biopsy specimens of patients of cancer oesophagus as well as controls. This analysis revealed a significantly higher immunopositivity (63%) of E6 oncoprotein of HPV 16/18 in carcinoma of the oesophagus. Immunoexpression of E6 oncoprotein of HPV did not alter significantly the degree of differentiation of the tumour. Seventy-seven percent of cases of oesophageal carcinoma showed strong immuno-staining for mutant p53 protein. A higher percentage (89%) of tissues showed immunoexpression of mutant p53 protein in conjunction with E6 oncoprotein of HPV 16/18 indicating a selective degradation of key cellular protein of p53 having regulatory properties which in turn leads to uncontrolled cellular proliferation. Therefore, coexpression of oncoprotein E6 of HPV 16/18 and mutant p53 protein may be considered as a "high risk" factor for progression to oesophageal malignancy.
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PMID:Immunohistochemical co-expression of human papillomavirus type 16/18 transforming (E6) oncoprotein and p53 tumour suppressor gene proteins in oesophageal cancer. 973 68

We histologically examined undifferentiated small cell carcinoma of the esophagus from 21 patients and used immunohistochemical methods for detection of chromogranin A and p53, bcl-2, and Rb oncoproteins. Nine (43%) of the 21 carcinomas consisted solely of undifferentiated cells, but heterogeneous components of in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma were observed in the other 12 (57%) tumors. Squamous cell carcinoma in situ was observed in the mucosa adjacent to the main tumor in 7 (50%) of the 14 resected esophageal specimens. An admixture of invasive squamous cell carcinoma and undifferentiated carcinoma was observed in 4 (19%) of the 21 tumors, and mucoepidermoid carcinoma was noted in one case. Chromogranin A staining yielded a positive reaction in two (10%) undifferentiated components but was negative in all heterogeneous components. Multiple sites of p53 immunopositivity were seen in the undifferentiated component of 17 (81%) of the 21 tumors, as well as in the in situ or invasive squamous cell carcinoma or mucoepidermoid carcinoma components of 9 (75%) of 12 tumors. Seven (33%) of the 21 tumors showed positive bcl-2 immunoreactivity in the small cell component, but all of the heterogeneous components were negative. Rb protein immunoreactivity was observed in the small cell component of one (5%) case and in 9 (75%) of the 12 heterogeneous components. Six (86%) of the seven in situ squamous cell carcinoma components were positive for Rb protein. Eighteen (86%) of the 21 patients died within 24 months of diagnosis. Two patients (10%) who survived for more than 24 months had received chemotherapy.
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PMID:Primary undifferentiated small cell carcinoma of the esophagus. 1002 52

Small cell carcinoma is a rare neoplasm in the esophagus. To evaluate cell proliferation activity and its underlying mechanisms in this tumor, we examined immunohistochemically 5 cases of small cell carcinoma of the esophagus (SCCE) for expressions of tumor suppressor proteins, oncoproteins and cell proliferation markers including p53, p21WAF1/CIP1, retinoblastoma (Rb) protein, bcl-2, Ki-67 and PCNA, and compared the results with those of 5 cases of small cell carcinoma of the lung (SCCL) and 10 cases of squamous cell carcinoma of the esophagus (SQCE). The prevalence and labeling index of p53-immunoreactivity tended to be higher in SCCE (4/5; 56.6%) and SCCL (4/5; 79.9%) than in SQCE (6/10; 48.8%). Expression of p21WAF1/CIP1 was observed in 2 of 10 cases of SQCE. In contrast, its expression could not be detected in any cases of SCCE and SCCL examined. Expression of Rb protein was observed in 9 out of 10 cases of SQCE, but not in any cases of SCCE and SCCL. SCCE and SCCL showed more frequent and intense immunoreactivity for bcl-2 than SQCE. In expression of cell proliferation markers (Ki-67 and PCNA), no remarkable difference was observed among SCCE, SCCL and SQCE. These results suggest that SCCE and SCCL could share some genetic alternations including mutation of p53, loss of Rb gene and overexpression of bcl-2, and these may be related to the similar biological potentials between the two. Furthermore, SCCE was different from SQCE in expression of Rb protein and bcl-2, and these two types of esophageal carcinoma could arise through different molecular mechanisms.
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PMID:Immunohistochemical analysis for cell proliferation-related protein expression in small cell carcinoma of the esophagus; a comparative study with small cell carcinoma of the lung and squamous cell carcinoma of the esophagus. 1021 9

A high incidence of synchronous esophageal or gastric carcinoma in preoperative patients with carcinoma of the oral cavity was reported. Esophageal carcinoma was found in seven out of 56 patients (12.5%) and gastric cancer in five patients (8.9%) by videoendoscopy aided with lugol staining in the esophagus and indigocarmine solution in the stomach, although all patients were completely asymptomatic for these lesions. All patients were male, regular drinkers and heavy smokers. The depth of invasion of such tumors was limited to either mucosa or submucosa. Those esophageal and gastric lesions beside the primary oral cancers were positive for p53 protein by immunohistochemistry. Careful preoperative evaluation of not only the esophagus but also the stomach should be a routine procedure in patients with carcinoma of the oral cavity.
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PMID:High incidence of synchronous cancer of the oral cavity and the upper gastrointestinal tract. 1052 14

Squamous-cell carcinoma of the esophagus (SCCE) shows geographic variations in incidence that are thought to reflect the etiological involvement of environmental or dietary risk factors. Mutations of TP53 are frequent in SCCE, and there is evidence that both the frequency and type of these mutations may differ from one geographic area to the other. Although SCCE is relatively rare in most parts of Thailand, the province of Songkhla (south Thailand) has been described as a high-risk area for SCCE. We have analyzed 56 SCCE cases from this area for TP53 mutations by denaturing gradient gel electrophoresis (DGGE, exons 5-8) and direct DNA sequencing. The same tumors were also analyzed for MDM2 gene amplification by differential PCR. TP53 mutations were detected in 23 cases (41%). In contrast, clear amplification of MDM2 was detected in only 2 cases (4%), both of which contained wild-type TP53. Comparison with published results from other geographic areas of high SCCE incidence revealed that the spectrum of TP53 mutations in south Thailand is similar to that observed in central China (Henan Province) but clearly differs from that of SCCE from western Europe (Normandy, France; northern Italy), with more G:T transversions and fewer mutations affecting A and T base pairs. These results suggest that SCCE from south Thailand and from central China may involve similar risk factors.
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PMID:TP53 mutations and MDM2 gene amplification in squamous-cell carcinomas of the esophagus in south Thailand. 1100 72

We recently encountered a patient with basaloid carcinoma of the esophagus with extensive node involvement. The patient died of hematogenous metastasis 6 months after surgery. The tumor expressed cytokeratin but did not express either Type IV collagen or laminin. Both tumor cells and metastatic lesions in the regional lymph nodes expressed p53, Bcl-2, and Ki-67 proteins, but did not express cyclin D1 proteins.
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PMID:An immunohistochemical examination of basaloid squamous cell carcinoma of the esophagus: report of a case. 1149 63

Small cell carcinoma of the esophagus is a rare and aggressive malignant tumor. Telomerase activation is common in human cancers. There is a lack of data on telomerase activity in esophageal small cell cancers. The present report studied the role of telomerase activity in esophageal small cell carcinoma. The clinicopathologic data of five patients with small cell carcinoma of the esophagus who underwent primary surgical treatment between 1991 and 2000 were studied. Telomeric repeat amplification protocol assays were used to investigate telomerase activity in these tumors. The proliferative activity (MIB-1) and p53 expression of these tumors were also studied using immunohistochemistry and correlated with the telomerase activity. All five small cell carcinomas showed detectable telomerase activity in the primary tumor. Two out of the five morphologically normal esophageal mucosae adjacent to the primary tumor had detectable telomerase activity. There was no correlation between the p53 expression, tumor stage, survival of patients, and the presence of telomerase activity. High MIB-1 expression in esophageal small cell carcinomas was associated with high telomerase activity. Telomerase activation is common in small cell carcinoma of the esophagus. This fact may find application in anti-telomerase treatment for this aggressive tumor.
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PMID:Telomerase activity in small cell esophageal carcinoma. 1155 25

Esophageal carcinoma is one of the most common gastrointestinal malignant neoplasms in the world. Recent advances in treatment modalities as well as surgical resection techniques have improved the changes of survival of patients with esophageal carcinoma, although the prognosis is worse than for the other gastrointestinal carcinomas. A more precise stratification beyond clinicopathological classification may help determine optimal treatment. The importance of p53 gene mutations in the pathogenesis of human esophageal carcinoma is well established, but it is still controversial whether the presence of p53 mutations adversely affects individual patient prognosis. In this study, we investigated the p53 mutations of esophageal carcinomas and their correlation with clinicopathologic factors. We employed a p53 yeast functional assay because it is highly sensitive and can detect mutations based on the actual function of the p53 gene, clarifying more precisely the role of this gene in esophageal carcinomas. We also studied young patients (< or =65 years old), because our previous study raised the possibility of differences in the importances in esophageal carcinogenesis in young and old patients. Of 43 young esophageal carcinoma patients (42 squamous cell and 1 undifferentiated carcinoma), 38 (88.4%) harbored p53 mutations. Twenty-seven missense and 11 null mutations were detected, but the presence of p53 mutations did not correlate with any clinicopathologic factor. However, the null mutation was a significant indicator of a poor outcome (P=0.0278). All except one patient who harbored null mutation died within 3 years after a macroscopically curative resection. These data suggest that the type of p53 gene mutation may be predictive of outcome in young esophageal carcinoma patients. Furthermore, null mutations causing loss of function of the gene product may play a more important role than missense mutations in tumor progression.
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PMID:p53 null mutations detected by a p53 yeast functional assay predict a poor outcome in young esophageal carcinoma patients. 1216 11


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