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)

Chemoradiotherapy is a multimodal therapy routinely used as a primary treatment for advanced esophageal cancer. However, it is beneficial only to patients who respond. To identify pretreatment markers predicting response and survival, we examined the expression of cell cycle regulatory molecules, p53, p21(Waf1/Cip1) cyclin D1, and CDC25B, in biopsy specimens from 76 patients with stage III and stage IV squamous cell carcinoma. Overexpression of p53, p21, cyclin D1 and CDC25B was observed in 58%, 30%, 28%, and 32% of patients, respectively. The expression of p21 correlated significantly with response to chemoradiotherapy (P = 0.0001). Survival of patients with p21-expressing tumors was better than that of patients with p21-negative tumors (P = 0.013). Expression of other genes was not significantly correlated with treatment response and survival. In patients with p53-negative tumors, survival of those patients with p21-positive tumors was significantly higher than that of those with p21-negative tumors (P = 0.0452), but no significant difference was found in patients with p53-positive tumors. Multivariate analysis revealed that p21 expression was an independent variable among pretreatment parameters in predicting survival. These results suggest that p21 expression is potentially useful for predicting the response to chemoradiotherapy and survival of patients with advanced esophageal squamous cell cancer.
Dis Esophagus 2004
PMID:Expression of p21(Waf1/Cip1) predicts response and survival of esophageal cancer patients treated by chemoradiotherapy. 1556 70

Barrett's columnar epithelium with dysplasia is the most important risk factor for adenocarcinoma of the distal esophagus. The molecular mechanisms responsible for progression of columnar metaplasia to dysplasia and invasive carcinoma are mostly unknown. We investigated expression of the tumor suppressor gene p53, E-cadherin expression and cell proliferation in the metaplasia-dysplasia-carcinoma sequence of esophageal adenocarcinoma. In 24 patients with R0-resected adenocarcinomas of the distal esophagus we evaluated the expression of E-cadherin (antibody HECD-1), mutated p53 (antibody DO1) and cell proliferation (antibody MiB1) by immunohistochemistry in sections of adenocarcinoma, columnar metaplasia, with and without dysplasia, and in squamous epithelium of the esophagus. No p53 immunoreactivity was seen in sections of normal squamous epithelium or columnar metaplasia. Fifty per cent of invasive adenocarcinomas stained positive for mutated p53. The p53 expression correlated with the T-category (P = 0.048) and the N-category (P = 0.024). There was a significant decrease in the expression of E-cadherin from columnar metaplasia to dysplasia and to esophageal adenocarcinoma (P < 0.0001). Expression of E-cadherin in columnar metaplasia without dysplasia was similar to that seen in normal squamous epithelium of the esophagus. The Ki-67 proliferation fraction increased significantly from normal squamous epithelium to columnar metaplasia to dysplasia and to invasive carcinoma (P < 0.001), with a marked expansion of the proliferative component. There was no correlation between cell proliferation, E-cadherin expression and the tumor stage. In contrast to the alterations in the p53 expression, a decreased E-cadherin expression and the expansion of the proliferative component represent an early phenomenon in the malignant degeneration of Barrett's esophagus. This might aid in the early detection of esophageal adenocarcinoma.
Dis Esophagus 2004
PMID:Malignant degeneration of Barrett's esophagus: the role of the Ki-67 proliferation fraction, expression of E-cadherin and p53. 1556 71

Most esophageal carcinosarcomas are diagnosed as so-called carcinosarcoma, in which individual elements may be derived from a single common ancestor cell, and there have been a few reports describing true carcinosarcoma originating from two individual stem cells. We describe a case of esophageal carcinosarcoma exhibiting neoplastic osteoid formation. Immunoreactivity for vimentin and p53 was limited to only the sarcomatous component and was absent in the carcinomatous component. Furthermore, a point mutation in exon 7 of the p53 gene was observed only in the sarcomatous component. Both sarcoma and carcinoma cells distinctively metastasized to different lymph nodes. These observations led us to diagnose the esophageal tumor as a true carcinosarcoma.
Dis Esophagus 2006
PMID:True carcinosarcoma of the esophagus. 1636 45

We study the expression of early growth response gene-1 (Egr-1 gene) in non-irradiated and irradiated human esophageal cancer tissues, and its relationship with the expression of C-fos, C-jun onco-proteins as well as Egr-1 target gene proteins P53, Rb and Bax expression. In situ hybridization (ISH) and immunohistochemistry (IHC) were used respectively to detect Egr-1 mRNA, Egr-1, C-fos, C-jun, P53, Rb and Bax proteins in 80 surgically resected non-irradiated and irradiated tumor specimens of esophageal squamous cell carcinoma. Egr-1 gene mRNA and Bax protein were located in the cytoplasm, whereas Egr-1, C-fos, C-jun, P53, Rb proteins were located in the nuclei. Egr-1 was expressed in nine out of 40 cases (22.5%) of non-irradiated and 23 of 40 cases (57.5%) of irradiated tumor specimens. No correlation was found between Egr-1 gene expression and C-fos, C-jun onco-proteins expression, neither was any correlation disclosed between Egr-1 gene expression with its target gene protein expression. Patients who underwent radiotherapy with Egr-1 overexpressed in their cancer tissue had better prognosis. Radiotherapy up-regulates Egr-1 expression in esophageal carcinoma. Egr-1 overexpression may be a potential radiation response gene marker and may play an important role in prognosis of esophageal squamous cell carcinoma.
Dis Esophagus 2006
PMID:Expression of Egr-1 gene and its correlation with the oncogene proteins in non-irradiated and irradiated esophageal squamous cell carcinoma. 1686 58

NDRG1 (N-myc downstream regulated gene-1) was reported to be necessary for p53-mediated apoptosis and to be regulated by PTEN (phosphatase and tensin homolog). In several cancers, it was suggested to be a tumor suppressor gene. Its significance in esophageal squamous cell carcinoma (ESCC) has not been studied. The objective of this study was to clarify the relation between clinicopathological and biologic factors in esophageal carcinoma and to determine the prognostic significance of the expression of NDRG1. Expression of NDRG1 mRNA was quantified by real-time reverse transcription polymerase chain reaction using a Lightcycler in 47 esophageal ESCC specimens. The data were analyzed with reference to clinicopathological factors. Among the esophageal cancer tissues, NDRG1 mRNA expression was significantly lower in tumors of more advanced pathological stage (0-I vs. II-IV; P = 0.0027) and local tumor invasion (T1-2 vs. T3-4; P = 0.0136). Patients who had low NDRG1 mRNA expression had a significantly shorter survival after surgery compared with patients who had high NDRG1 mRNA expression (log-rank test, P = 0.0478). Impaired NDRG1 expression may lead to more aggressive invasion of ESCC.
Dis Esophagus 2006
PMID:Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma. 1706 88

It is reported that surveillance of serum p53 antibody (Ab) is a useful marker in detecting esophageal squamous cell carcinoma (ESCC). But there is little reported about prognostic significance of serum p53-Ab in postoperative patients with ESCC. The aim of this study is to evaluate the significance of preoperative serum p53-Ab as a marker of early recurrence after curative resection for ESCC. Enzyme-linked immunosorvent assay (ELISA) was used to analyze serum p53-Ab before treatment in 44 patients with ESCC. Carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were examined by immunoradiometric assay. The patients who were strongly positive and positive in serum p53-Ab were more likely to have early recurrence after curative resection than seronegative patients. There were no significant correlations between CEA, SCC-Ag positivity and early recurrence. We found that serum p53-Ab was useful to predict a risk of early recurrence after curative surgical resection for ESCC.
Dis Esophagus 2007
PMID:Serum p53 antibody as a predictor of early recurrence in patients with postoperative esophageal squamous cell carcinoma. 1743 94

Barrett's esophagus, a metaplasia predisposed to malignant transformation, has been studied in vitro using esophageal adenocarcinoma cell lines. However, findings in such transformed cells may not be applicable to the non-neoplastic cells of benign Barrett's esophagus. Therefore, we have developed and characterized a Barrett's cell line derived from a patient without malignancy or dysplasia. Human Barrett's epithelial cells were immortalized with the insertion of hTERT (human telomerase reverse transcriptase) using a Cre-lox recombination system. We then examined properties of this continuous cell line, such as in vitro tumorigenicity, growth patterns, histological differentiation characteristics, karyotype, and checkpoint arrest mechanisms (e.g., p16, p21, and p53). Non-neoplastic Barrett's epithelial cells infected with hTERT (BAR-T cells) have been sustained in culture beyond 200 population doublings. BAR-T cells maintain a diploid chromosome number and exhibit non-neoplastic properties, such as contact inhibition and anchorage-dependent growth. BAR-T cells express differentiation Barrett's epithelial markers, such as villin and cytokeratins 4, 8 and 18, and stain positive for Alcian blue, indicating the presence of mucin-producing cells. Expression of checkpoint arrest proteins p21 and p53 are intact, while p16 expression is lost. Thus, we have created a human Barrett's cell line that is not malignantly transformed, and yet can be maintained indefinitely in culture. BAR-T cells are diploid, have histological differentiation markers characteristic of benign Barrett's epithelium, and also maintain appropriate expression of p21 and p53. This cell line should be a useful model for the study of the early events in carcinogenesis in Barrett's esophagus.
Dis Esophagus 2007
PMID:Characterization of telomerase-immortalized, non-neoplastic, human Barrett's cell line (BAR-T). 1750 24

P73, a p53 homolog, has some p53-like activities and plays an important role in modulating cell cycle, apoptosis and DNA repair. The two linked polymorphisms in the non-coding region of exon2 of p73 gene, named G4C14-A4T14, may alter translation efficiency of the gene. The transcription of p73 gene is initiated by three promoters, termed P1-P3. There is a single nucleotide substitution (-386G/A) in the P3 promoter region with unknown function. To test the hypothesis that the genetic variations in the exon2 and P3 promoter play a role in the etiology of esophageal squamous cell carcinoma (ESCC), we conducted a population-based case-control study in 348 ESCC patients and 583 healthy controls from a high incidence region of Hebei province, China. The p73 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP). The results showed that the family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC (the age, sex and smoking status adjusted OR = 2.02, 95% CI = 1.54-2.67). The overall distribution of the p73 genotype, allelotype and haplotype in cancer patients and controls were not significantly different (all P-values are above 0.05). Stratification analysis by smoking status and family history of UGIC also did not show the significant influence of the polymorphisms on the risk of ESCC development. The results suggested that the p73 exon2 G4C14-A4T14 and P3 promoter -386G/A polymorphisms might not be used as potential markers to predicate the risk of ESCC development in northern China.
Dis Esophagus 2007
PMID:The p73 polymorphisms are not associated with susceptibility to esophageal squamous cell carcinoma in a high incidence region of China. 1761 76

The aim of our study was to investigate the incidence of duodeno-gastroesophageal reflux-induced malignant transformation in a series of duodeno-esophageal anastomosis operations in rats. This surgical method provides a model for reflux-induced esophageal pathologies, without carcinogen administration. The study design included the follow-up of 31 cases. Thirty weeks of duodeno-gastroesophageal reflux disease significantly increased the risk of the development of Barrett's esophagus, and reflux-induced esophageal adenocarcinoma formation was evident in four animals. In one of these particular cases, a superficial squamous cell cancer was noted in close vicinity to the adenocarcinoma formation. For further analysis, a detailed immunohistochemical staining protocol was used. The immunophenotypes revealed cyclin D1 expression (nuclear positivity in 35% of all the squamous cells), p53 protein accumulation (50% nuclear positivity), with a low expression of cox-2, and negative c-erbB2 staining in the squamous carcinoma cells. The specialized intestinal metaplasia and mucinous adenocarcinoma cells exhibited exclusively diffuse cox-2 positivity (90% of all glandular cells) and weak focal c-erbB2 (5%) staining, without cyclin D1 expression or p53 protein accumulation. Real-time polymerase chain reaction was applied to quantify the abundance of p53, cyclin D1 and cox-2 mRNAs in this biopsy. The most dramatic changes were observed in the level of expression of cyclin D1 (a 9.08-fold expression as compared with the non-treated esophagus samples), while the p53 and cox-2 gene expressions were increased by 1.61 and 2.45-fold, respectively, relative to the non-treated samples. The results afford evidence of the simultaneous activation of more than one possible carcinogenetic pathway in experimental gastroesophageal reflux disease. Synchronous neoplasm formation with different growth pattern characteristics is a rarity in humans, and this phenomenon suggests that the presented model is a suitable means of mimicking the whole spectrum of human gastroesophageal reflux disease pathology.
Dis Esophagus 2007
PMID:Simultaneous adeno- and squamous cell carcinoma with different phenotypic profiles in a rat model of chronic gastroesophageal reflux. 1761 79

The prognosis of esophageal squamous cell carcinoma is primarily determined by staging. Although radiological methods have revealed lymph node metastasis preoperatively, these radiological findings cannot be correlated with pathological staging. The aim of this study was to compare the expressions of p53, vascular endothelial growth factor C (VEGF C) and p21 with lymph node metastasis in preoperative endoscopic biopsy and postoperative resection material. Tissue samples were taken from 40 patients who had undergone endoscopic biopsies and radical esophagectomies. The expressions of p53, VEGF C and p21 proteins in these sections were immunohistochemically examined. The expression of each antibody was characterized as a negative or positive reaction according to the pattern and intensity of semiquantitative immunostaining. The staining pattern of antibodies was divided into three groups: < 10% cancer cells were accepted to be (-), 10-50% were (+), heterogenous and > 50% were (+ +), homogenous. For each antibody, statistical correlation with conventional prognostic parameters such as localization, microscopic grade, stage, pathological lymph node metastasis and survival, were investigated. p53 expression was observed in 65.5% (19/29) of lymph node positive cases, whereas p53 was in 50% (20/40) of cases. VEGF C was in 65% (26/40) and p21 was in 15% (6/40) of cases. p53 has the specificity of 90.9% and sensitivity rate of 65.5% in detecting lymph node metastasis and positive predictive value was 95%. Expression of p53 was significantly correlated with stage and lymph node metastasis (P = 0.02 and P = 0.03, respectively). Prediction of lymph node metastasis by p53 was correlated independently and in coexpression with VEGF C (P < 0.01). There was no relation detected between p21 and other parameters. In esophageal squamous cell carcinoma (SCC), p53 and VEGF C expressions were correlated with pathologically positive lymph nodes. When preoperative staging has been insufficient in esophageal carcinoma cases, immunohistochemical analysis of p53 and VEGF C staining in tissues could be an aid to clinicians regarding lymph node metastasis.
Dis Esophagus 2007
PMID:Expressions of p53, VEGF C, p21: could they be used in preoperative evaluation of lymph node metastasis of esophageal squamous cell carcinoma? 1776 Jun 50


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