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)

We have studied expression of p53, a tumor suppressor gene, by using both immunohistochemistry and in situ hybridization in 20 cases of squamous cell carcinoma of the esophagus. Immunohistochemical analysis was performed by using monoclonal antibody pAb1801. Immunoreactive p53 was observed in the nuclei of the tumor cells in 17 cases. We used 35S-labeled anti-sense single-stranded synthetic oligonucleotide probe ON102, which hybridized with DNA sequence near the 5' end of p53, for in situ hybridization. In all the cases of invasive squamous cell carcinoma studied, no significant accumulation of p53 hybridization signals was observed in carcinoma cells. This result indicates that overexpression of p53 observed by immunohistochemical staining is not due to an increase in the steady-state level of p53 mRNA in frank carcinoma cells. In six cases of morphologically normal esophageal mucosa distant from carcinoma, accumulation of hybridization signals was observed in basal and parabasal cells of the mucosa. The mucosa of these cases was negative for p53 immunoreactivity except for one case showing sporadic positivity. Accumulation of hybridization signals was observed in foci of squamous dysplasia not associated with invasion in three cases.
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PMID:In situ hybridization and immunohistochemistry of p53 tumor suppressor gene in human esophageal carcinoma. 151 62

Esophageal squamous cell carcinoma (ESC) samples from patients residing in Uruguay and in Normandy, France, where alcoholic beverages and tobacco smoke are major risk factors, were analyzed for point mutations in the p53 tumor suppressor gene. Among 34 tumors (15 from Normandy and 19 from Uruguay) 15 point mutations in the p53 gene that result in amino acid substitutions or chain termination were identified by polymerase chain reaction amplification of exons 5-8 and direct DNA sequencing. Base substitutions in ESC from these high-incidence areas are dispersed over the midregion of the p53 gene. There are differences between ESC and other types of gastrointestinal cancer in the nature of frequent base substitutions. CpG to TpG transitions were far less prevalent in these ESC than in colorectal tumors, whereas G to T transversions, rarely found in colon cancers, were found in one-fourth of the ESC samples. Base substitutions at A:T pairs constitute an important fraction of ESC p53 mutations, in contrast to mutation patterns in most other types of solid tumors. In contrast to the frequent mutation of the p53 gene in these samples, no mutations in the H-, K-, or N-ras genes were found in 16 tumors from Uruguay by direct sequencing of exons in which transforming mutations are known to occur. A previous study on ras mutations in ESC from France was also negative (M. C. Hollstein et al., Cancer Res., 48: 5119-5123, 1988). The role of distinct etiological factors in generating these differences and the potential for linking patient exposure histories with patterns of p53 mutations in high risk populations are considered.
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PMID:Genetic analysis of human esophageal tumors from two high incidence geographic areas: frequent p53 base substitutions and absence of ras mutations. 185 26

Confocal laser scanning microscopy (CLSM) has become an exciting new instrument with rapidly expanding potential for application to the morphological examination. As an initial step of examining the possible values or potentials of CLSM observations in diagnostic pathology materials, we applied CLSM to the analysis of immunolocalization of proliferating cell nuclear antigen (PCNA), p53 and cytokeratin, and eosin and DNA fluorochrome propidium (PI) stain in cell smears obtained from 20 cases of squamous cell carcinoma of the esophagus. Superior contrasts and resolution were obtained in confocal images than in nonconfocal ones in immunocytochemistry, eosin, and PI stain. In immunocytochemistry, CLSM demonstrated subcellular localization of antigens examined, cytokeratin as coarse and fine intracytoplasmic fibers, PCNA as diffuse intranuclear localization, and p53 as heterogeneous intranuclear localization which appeared to be associated with chromatin structure. Optical sectioning of a specimen by the rejection of out-of-focus noise revealed three dimensional structure of cell clusters of squamous cell carcinoma. With eosin and PI as dyes for stain, three dimensional structures of any clusters on cell smears can be obtained. CLSM has vast potentials in the analysis of diagnostic cytology materials, including immunocytochemistry.
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PMID:Confocal laser scanning microscopy in cytopathology. 750 62

Esophageal cancer is an important problem in the United States. It results in more deaths (over 10,000 annually) than rectal cancer. Furthermore, the incidence of esophageal adenocarcinoma is increasing at a rate faster than that of nearly any other cancer and the reasons for the increase are not well understood. A variety of tumor-suppressor genes (including p53, APC, DCC and Rb) and proto-oncogenes (including prad1, EGFR, c-erb-2 and TGF alpha) may be involved in the development and progression of esophageal cancer. Clinical prognostic factors include stage, Karnofsky performance status, sex, age, anatomic location of the tumor, and degree of weight loss. A new staging system based on depth of wall penetration and lymph node involvement correlates well with prognosis for patients undergoing esophagectomy. Newer staging procedures including endoscopic ultrasound as well as the use of minimally invasive surgery, such as thoracoscopy and laparoscopy, may allow accurate staging without esophagectomy. Surgical resection provides excellent palliation; however, the chance for cure with esophagectomy alone is only 10% to 20%. Adjuvant treatment with pre- or postesophagectomy radiation may improve local-regional control but does not improve survival. Nor has preoperative chemotherapy been shown to improve survival; however, it remains an active area of investigation. Multimodality therapy, namely, chemotherapy and radiation (chemoradiation), given concurrently prior to surgical resection shows promise, with one study indicating a 5-year survival of 34%. A complete pathologic response to chemoradiation correlates with improved survival. Chemoradiation has been shown to be superior to radiation as primary management of esophageal cancer. There has been no successfully completed randomized trial of surgery versus definitive radiation or chemoradiation. However, chemoradiation represents a reasonable alternative to esophagectomy in the primary management of squamous cell carcinoma of the esophagus and chemoradiation also appears to be effective in the treatment of patients with adenocarcinoma of the esophagus, offering significant palliation and a chance for long-term survival as well. Randomized studies of preoperative chemoradiation versus surgery or versus chemoradiation alone are needed. The treatment of advanced esophageal cancer must be directed toward palliation of symptoms. Newer endoscopic techniques, including the use of expansile metal stents, laser ablation, intraluminal high-dose rate brachytherapy, BICAP tumor probe, or photodynamic therapy, offer selected patients short-term palliation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Esophageal cancer. 753 69

Esophageal squamous cell carcinoma is a form of cancer occurring most commonly in males, particularly those living in some areas of Asia, Africa, and western Europe. In some of these tumors, a sequence alteration has been identified in the coding region of the TP53 gene which is known to inactivate the tumor suppressor function of its product. Using a GC clamp (i.e., a GC rich domain) denaturing gradient gel electrophoresis assay we have been able to identify sequence modifications in 27 of the 32 tumor samples analyzed (84%). Most of the mutations occur in exon 6, a region of the gene which has not previously been reported as being a hot spot for the mutations of other cancers. Twelve of the mutations reported here have not been described in other types of tumors and these consist mostly of frameshift or splice mutations. The distribution of mutations [transitions (45%), transversions (34%), and frameshift (21%)] suggests that the etiological contribution of genotoxic factors might be complex and might associate different exogenous and endogenous mutagen exposures.
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PMID:TP53 gene mutation profile in esophageal squamous cell carcinomas. 824 31

Primary squamous cell carcinoma of the endometrium (ESCC) is extremely rare. There has been no report of human papillomavirus (HPV) detected in ESCC. A 64-year-old Japanese female underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and dissection of the pelvic, para-aortic, and bilateral inguinal lymph nodes. The tumor was confined to the endometrium, without invasion of myometrium or cervix. The endometrium was seen to be replaced by moderately differentiated squamous cell carcinoma, without any adenocarcinomatous element. Polymerase chain reaction amplification produced a 244- to 256-bp DNA fragment from the L1 region of the HPV genome. The amplification products were restricted, and the restricted fragment length polymorphism patterns were analyzed. The squamous cell carcinoma DNA was amplified for each exon, 5 through 8, of the p53 gene. The amplification products were used in single-stranded conformation polymorphism analysis. The tumor described showed the presence of HPV DNA. This amplified fragment was further purified by extraction from agarose gel, and the DNA was sequenced. Comparison of the fragment DNA sequence with known PV sequences showed that it had been amplified from HPV type 31. This is the first detection of HPV DNA in ESCC. Despite previous reports, HPV cannot not be excluded as a possible factor in the development of the malignancy.
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PMID:Squamous cell carcinoma of the endometrium with human papillomavirus type 31 and without tumor suppressor gene p53 mutation. 910 11

The significance of intraepithelial carcinoma concomitant with esophageal squamous cell carcinoma during carcinogenesis and progression of the tumor has been discussed diversely. The purpose of the current study was to elucidate the relation between p53 protein expression and the growth pattern of the squamous cell carcinoma of the esophagus with attention to coexistence of intraepithelial carcinoma. Seventy cases with squamous cell carcinoma of the esophagus surgically resected without preoperative adjuvant therapy, including 49 cases with intraepithelial carcinoma contiguous to the invasive lesion, were analyzed immunohistochemically for p53 expression. Positive immunoreactivity of p53 was found in 36 (51.4%) of 70 cases. The frequency of p53 protein expression in cases with intraepithelial carcinoma (65.3%; 32/49) was significantly higher than that (19.0%; 4/21) in cases without intraepithelial carcinoma (p<0.001). The value of invasion coefficient, which indicates a ratio of the area of invasive cancerous lesion occupied in the whole lesion, in the cases with p53 protein expression was significantly smaller than that in the cases without p53 protein expression (p<0.001). In conclusion, p53 protein expression was found to be significantly related to the coexistence and spreading of intraepithelial carcinoma contiguous to squamous cell carcinoma of the esophagus.
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PMID:Significance of p53 protein expression in growth pattern of esophageal squamous cell carcinoma. 968 20

We evaluated the clinical significance of p53, p27 and PCNA expressions in esophageal squamous cell carcinomas. Operative specimens obtained from 70 patients with esophageal squamous cell carcinomas were investigated by staining with antibodies against p53, p27 and PCNA. The correlations among p53, p27 and PCNA expression, clinicopathologic factors and prognosis were studied. The expression of p53 was observed in 55.7%, and it did not correlate to histologic classification, growth pattern, and lymphatic invasion. The expression of p27 was observed in 48.6%, and it correlated to lymph node metastasis. The PCNA positive index (PCNA-PI) was high in the p27 negative cases. The p53 positive and p27 negative group revealed the worst survival rate among groups. Therefore, the p27 positive case, often associated with well differentiated carcinoma, tends to have a slower tumor-growth rate and better prognosis. It is suggested that immunohistochemical assessment on the p53 and p27 expressions would be useful to the recognize the malignant potential and differentiation of squamous cell carcinoma of the esophagus.
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PMID:[Immunohistochemical study of p53, p27 and PCNA expression in esophageal cancer]. 970 5

Esophageal squamous cell carcinoma (ESCC) demonstrates wide regional variation in incidence and causal associations. Human papillomavirus (HPV) has been implicated in ESCC, particularly the sub-types 16 and 18. Transforming proteins E6 and E7 from these high risk sub-types, interact with p53 protein and Rb protein respectively, leading to loss of function of these tumor suppressor gene products. These interactions further lead to inactivation of the growth suppressive effects of the p53 and Rb proteins, resulting in abnormal proliferative states. p53 protein expression has been found in both HPV-positive and -negative tumors, indicating that HPV and p53 protein expression are not mutually exclusive and can occur together in the same tumor. It has been observed that HPV plays a more significant role in esophageal carcinogenesis in geographic areas with a high prevalence of the disease. A variation in the association between HPV and ESCC worldwide may be due to environmental and geographic factors, or to genetic susceptibility to esophageal HPV infections. Variations in the sensitivity of techniques used in the detection of the virus and in the methodology for processing the tumor tissues, may also be responsible for global differences. Esophageal carcinogenesis is a complex multistep process with a multifactorial etiology. Infection with oncogenic HPV types may be an integral part in a multistep process that leads to ESCC.
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PMID:The role of the human papilloma virus in esophageal cancer. 983 8

Esophageal SCC is a complex disease involving multiple etiologic factors. A number of preventive approaches could be taken to reduce the occurrence of the disease including changes in lifestyle and improved nutrition, for example, the inclusion of higher quantities of fruits and vegetables in the diet. Unfortunately, these primary prevention approaches are not easily implemented and often fall short in achieving marked reductions in disease occurrence. Chemoprevention offers another approach to reducing the risk of esophageal SCC that is likely to be useful, even though the clinical trials to date have not resulted in the identification of agents that produce marked inhibitory effects on the development of the disease. Given esophageal SCC's complex etiology, it would appear that the most effective chemoprevention strategy would be to employ agents that reduce mutational events associated with exposure to esophageal carcinogens in combination with agents that inhibit the progression of epithelial dysplasia to esophageal SCC. The feasibility of addressing carcinogen-induced mutational events is underscored by the fact that many of the suspected esophageal carcinogens are known, and inhibitors of these carcinogens have been identified in animal model systems. In addition, biomarkers to assess the efficacy of anti-initiation agents, such as levels of phase I and II enzyme activities and of carcinogen: DNA adducts, can be measured. The identification of agents that inhibit the progression of dysplastic lesions to esophageal SCC has proven difficult; however, the results of the trial with ATB and retinamide are encouraging. Clearly, it seems important to identify the active chemopreventives in the antitumor-B herbal mixture. Further studies to identify strong inhibitors of tumor progression in the rat model for esophageal SCC are also needed. Biomarkers of cell proliferation (e.g., PCNA, Ki67), cell differentiation (keratins), apoptosis, gene expression (EGFR, cyclin D1, p53), and nuclear/nucleolar morphometry can be used in studies to assess the efficacy of chemopreventives to either reverse esophageal dysplastic lesions or slow their rate of progression. The development of viable approaches toward the chemoprevention. of esophageal SCC is truly an important goal in view of the poor prognosis of this disease.
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PMID:Clinical models of chemoprevention for the esophagus. 988 21


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