UNIPROT:P04637 - FACTA Search

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Query: UNIPROT:P04637 (p53)
77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether a tumor suppressor gene of importance to epithelial ovarian cancer resides on the X chromosome, we examined loss of heterozygosity (LOH) in 123 epithelial ovarian cancer cases. In 54 such cases, we examined LOH at 26 loci on the human X chromosome. In eight cases, we examined LOH in 14 loci and in 61 cases we examined LOH in 13 loci. Matched DNA samples from tumors and corresponding normal tissues were analyzed by polymerase chain reaction (PCR) amplification of microsatellite markers. Frequent losses were found in epithelial carcinomas at the Xq25-26.l region, including DXS1206 (34.5% loss in informative cases), DXS1047 (27.7%), HPRT (24.1%), and DXS1062 (33.3%). The minimum overlapping region of LOH was approximately 5 megabases (Mb), flanked by DXS1206 (Xq25) and HPRT (Xq26.1). The methylation status of the remaining allele of the androgen receptor gene in the tumors exhibiting LOH at the Xq25-26.1 region suggested that the loss was exclusively in the inactive X chromosome. We next determined whether a significant relationship exists between Xq LOH and other parameters, including histologic grade and/or clinical stage of the tumors and LOH at TP53. The Xq LOH had a significant association with grade 2 to 3 tumors at stages II to IV. Sixteen of 18 cases that showed Xq LOH revealed LOH at the TP53 locus, and 45% of tumors exhibiting LOH at TP53 showed Xq LOH. These results suggest that there may be a tumor suppressor gene or genes which escape inactivation of the X chromosome at Xq25-26.1, and that the loss of the gene(s) at Xq25-26.1 is frequently accompanied by loss of the TP53 or loss of another gene on chromosome 17. These losses may contribute to the progression from a well-differentiated to a more poorly differentiated state or to metastatic aggressiveness.
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PMID:Loss of heterozygosity at chromosome segment Xq25-26.1 in advanced human ovarian carcinomas. 936 30

The predictive value of p53 and K-ras-2 mutational genotyping in determining tumor aggressiveness and survival in patients with endometrial carcinoma (EC) was retrospectively evaluated using a molecular genotyping approach on fixative treated tissue specimens. Two groups of patients with EC were selected based upon length of survival. Group A consisted of 14 patients that died within 3 years of initial diagnosis and treatment (mean survival of 1.1 years). Group B consisted of 18 patients that survived beyond 3 years (mean survival of 4.7 years). Clinicopathologic features including clinical stage, histologic type, and combined nuclear and architectural grade of each tumor were statistically analyzed with respect to oncogene/tumor suppressor gene alterations. The majority of carcinomas in group A were serous (57%), stage III or IV (93%), and high combined grade (93%). Group B consisted mostly of endometrioid (89%) and low-grade carcinomas (83%); 56.1% were stage III or IV. K-ras-2 point alterations were found in 2 (14%) and 4 (22%) patients from group A and B respectively; the spectrum of K-ras-2 genotypes was similar in both groups. p53 gene mutations were identified in 9 (64%) and 1 (6%) patient from group A and B respectively. p53 staining in group A tended to be of strong intensity and diffuse distribution, being associated with the presence of point mutations, mainly in exon 8. Only a single group B tumor exhibited point mutational change. The presence of p53 mutations strongly correlated with short survival (p <0.05) but the finding of K-ras-2 alterations did not. p53 genotyping has potential prognostic value in EC and can be used along with histopathologic type and histologic grade to identify subsets of more aggressive tumors and to guide the treatment.
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PMID:Prognostic value of p53 and K-ras-2 topographic genotyping in endometrial carcinoma: a clinicopathologic and molecular comparison. 942 Oct 75

Diagnosing and monitoring pancreatic cancer is an ongoing challenge. Conventional markers such as tumor-associated antigens might be supplemented by molecular markers such as gene mutations and growth factor/growth factor receptor alterations in the future. Tumor-associated antigens can easily be measured by different EIA/ELISA systems, but the analysis of gene mutations, growth factors and their receptors requires advanced molecular techniques. CA 19-9 is the most widely used conventional marker for pancreatic cancer and is a useful tool in the diagnosis and follow-up of patients after tumor resection. Nonetheless, its role in detecting early pancreatic cancer is limited. The detection of K-ras and p53 mutations, which occur in about 90 and 50% of pancreatic cancers, respectively, in blood, stool, or bile samples, seems to be a promising approach in the diagnosis. Growth factor and growth factor receptor alterations are often associated with increased tumor aggressiveness and shorter survival following tumor resection. To date the analysis of growth factors/growth factor receptors in pancreatic cancer has not entered clinical use, but further molecular characterization of pancreatic cancer is necessary for earlier and more accurate diagnosis and it may result in new treatment options.
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PMID:Molecular versus conventional markers in pancreatic cancer. 943 2

Recent preclinical and clinical data suggest that TP53 status and TP53 mutations may be important in determining tumour aggressiveness and therapy response. In this study we investigate the feasibility of a structural and quantitative analysis of TP53 on fine-needle aspiration (FNA) material obtained from 31 consecutive female patients with breast carcinoma, enrolled in a primary chemotherapy protocol. Tumours were screened for p53 protein overexpression and TP53 mutations (exons 5-8) using immunocytochemistry, polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing analyses, and finally using fluorescence in situ hybridization (FISH) analysis. Positive nuclear staining was identified in six cases whereas mutations were detected in nine. Although the immunoreactive pattern fitted fully with the characterized TP53 mutation type, the considerable number of null p53 mutations (i.e. four) coupled with the lack of information regarding the localization of TP53 mutations make immunocytochemistry an inadequate indicator of TP53 function deregulation. Combining molecular and FISH analyses, we detected three cases with TP53 deletion and one case with deletion and mutation. Finally, DNA static-image analysis performed on 29 cases showed aneuploidy in 26 cases, which included all TP53-mutated cases. The present results show that FNA may assist clinical decisions by allowing the evaluation of a variety of biological parameters relevant for prognosis and treatment planning.
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PMID:Detection of TP53 mutation, loss of heterozygosity and DNA content in fine-needle aspirates of breast carcinoma. 945 57

Merkel cell carcinoma (MCC) is a frequently aggressive primary cutaneous neuroendocrine malignancy. We investigated 3 cell proliferation markers which may be useful in predicting the aggressiveness of MCC: 1) p53, a tumor suppressor protein, 2) Ki-67, a marker of cell cycling, and 3) proliferating cell nuclear antigen (PCNA). Twenty patients with MCC were studied. The 3 cell proliferation markers were studied by immunoperoxidase. Clinical and immunoperoxidase results were tabulated according to recurrence or death from disease. Of the 20 patients, 10 experienced recurrence, and 10 did not. Seven tumors were positive for p53. We found correlations between recurrence and death in MCC patients, between p53 positivity and recurrence/death, and between p53 positivity and head/neck primary sites. We found no correlation with recurrence by gender or primary site. PCNA was positive in only 1 patient, while Ki-67 was positive in all patients, making these 2 markers unsuitable for predicting recurrence. Further clinical studies will be helpful to confirm and refine the application of this test. Prognostic information from such studies may be useful in planning observation and treatment for patients in the future.
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PMID:Proliferation markers and prognosis in Merkel cell carcinoma. 950 39

Current dilemmas for physicians managing patients with localized prostate cancer include deciding: (1) which patients need aggressive treatment; (2) what treatment options are best for a given patient; and (3) what treatment outcomes can be expected. This article reviews our ability to prognosticate outcome (including pathological stage and disease-free survival rate) in patients with clinically localized adenocarcinoma of the prostate (AJCC, stage T1-T2. N0, M0) subsequent to analysis of several contemporary series involving patients treated with radical prostatectomy and external-beam radiation therapy. Pretherapy prostate-specific antigen (PSA) level (< or =4 ng/mL or >20 ng/mL) and Gleason score (< or =4 or > or =8) as individual variables provide independent prognostic information for only a subset of patients undergoing radical prostatectomy and external-beam radiation therapy. Pathological stage is the most powerful predictor of outcome following radical prostatectomy, and its prediction (organ-confined vs. seminal vesicle or lymph node involvement) is aided by knowledge of clinical stage, Gleason score, and PSA level. Planned systematic biopsies also provide useful prognostic information for the prediction of pathological stage and tumor volume, as well as providing additional tissue for pathological assessment of tumor heterogeneity. Several novel markers of biological aggressiveness are associated with critical steps of the metastatic cascade (growth, invasion, angiogenesis, and resistance to apoptosis) and include the p53 tumor suppressor gene, the bcl-2 proto-oncogene, markers of increased proliferation (Ki-67), apoptosis, and angiogenesis (microvessel density). Their evaluation in clinical specimens is currently being used to prognosticate outcome. Current clinical and pathological parameters provide a "ballpark" estimate of outcome for patients with clinically localized prostate cancer. Further elucidation of the critical molecular events associated with prostate cancer progression and metastasis should help in identifying molecular markers that more accurately predict the prognosis for an individual patient with clinically localized prostate cancer.
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PMID:Prognostic markers in clinically localized prostate cancer. 956 75

Recent studies suggest that a balance may exist between the cell cycle arrest and apoptosis-inducing functions of the p53 tumor suppressor gene. Adenoviral p21 transduction attenuates apoptosis, whereas deletion of the p21 gene promotes it, and p21-null xenografts respond better than isogenic p21-wild type tumors to irradiation. Hence, the role of p53 in dictating the clinical response to radiotherapy and chemotherapy may be more complex than previously thought. We have analyzed survival and radiation response (regrowth-free period) of 42 patients with glioblastomas whose p53 status was determined by a sensitive yeast functional assay. Multivariate analysis revealed that p53 mutation is associated with longer survival (P < 0.02). Among 36 radiation-treated patients, the regrowth-free period after treatment was significantly longer for tumors with p53 mutations (P < 0.0001), and p53 mutation was the sole independent factor predictive of radiotherapeutic response (P < 0.01). Survival time after regrowth was independent of p53 status, suggesting that the difference in survival was related to the treatment rather than to the intrinsic aggressiveness of the tumor. Thus, in this Northern Japanese population, p53 mutation is a marker for better radiation response in glioblastomas, and this results in significantly longer survival.
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PMID:Selective sensitivity to radiation of cerebral glioblastomas harboring p53 mutations. 958 14

A comparison was made of the staining intensities of selected immunohistochemical proliferating antigens (p53, PCNA, Ki67), DNA flow-cytometry and ultrastructures of neoplastic cells from 120 cases of laryngeal cancers. Clinically very advanced tumors were in the majority (T3, 43%; T4, 18%). A 5-grade scale was adopted to evaluate the level of immunohistochemical staining of the carcinoma cell nuclei. Positive staining was obtained in 70% for p53, 57% for Ki67 and 80% for PCNA. Sixty-two percent of the cases were DNA-diploid and 38% DNA-aneuploid. The DNA-diploid carcinomas were accompanied by enlargement of the cell nuclei, preservation of wide margins of nuclear heterochromatin, enlargements of the nuclear areas and increases in the number of nuclei. In the aneuploid-polyploid cancers the nuclei had a substantial polymorphism, with large cleaved nuclei showing significant variations in size and having a nuclear envelope. A frequent finding was euchromatization of chromatin. Dense chromatin appeared in the form of small clumps spread over the whole area of these irregular nuclei. Enlargement and activation of nucleoli were found. There was a positive (chi-square) correlation between T- and N-stage and immunohistochemical staining. There was also a positive correlation in staining intensity between p53, Ki67 and PCNA markers and strong correlation between these markers for proliferative activity and the degree of aggressiveness of a tumor.
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PMID:[Retrospective analysis of selected tumor markers (p53, PCNA, Ki67; DNA ploidy) and ultrastructure in patients with larynx carcinomas]. 958 28

It has now been clearly established that quantitative immunohistochemical methods applied to tumour angiogenesis under suitable quality control conditions are a powerful prognostic tool for use in the initial assessment of breast carcinomas. Appropriate parameters for predicting the aggressiveness of tumours and their sensitivity to treatment are, however, still required. To determine whether the microvessel count (MVC) may serve to predict the chemotherapeutic response, a retrospective study was carried out on a series of 162 patients with breast carcinoma, who were all treated with the same standard adjuvant chemotherapy. Angiogenesis was assessed by performing CD31 immunostaining and MVC per mm2. Several other factors such as P53, ERBB2, BCL2, and Ki67 were also measured, and their prognostic value was compared with that of the MVC. The MVC was not found to be correlated with any of the other prognostic parameters, but turned out to be of great prognostic value whatever the threshold value chosen, which suggests that it is continuously valid at all levels. The median value of the MVC (43.5 per mm2) divided this series into two significantly different prognostic categories, in terms of both disease-free survival (P = 0.0002) and overall survival (P = 0.037). Univariate analysis showed that most of the parameters analysed were of prognostic value regarding the disease-free survival, namely grade (P = 0.029), mitotic index (P = 0.049), size (P = 0.015), oestrogen receptors (P = 0.022), progesterone receptors (P = 0.018), P53 (P = 0.0045), ERBB2 (P = 0.046), and Ki67 (P = 0.0008). As regards overall survival, grade and ERBB2 showed a loss of prognostic value. In multivariate analysis on disease-free survival, the MVC was the most accurate prognostic factor (RR = 2.64), followed by Ki67 (RR = 2.06) and P53 (RR = 1.69). With respect to overall survival, the MVC ranked third among the prognostic parameters analysed. Standard chemotherapy did not reduce the high prognostic value of the MVC performed on tumour angiogenesis. This suggests that the MVC may predict the degree of resistance to chemotherapy. Patients with high levels of angiogenesis, particularly node-negative patients, might therefore be able to benefit from adjuvant therapy of another kind.
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PMID:Angiogenesis as a prognostic marker in breast carcinoma with conventional adjuvant chemotherapy: a multiparametric and immunohistochemical analysis. 960

Pleomorphic adenoma of the lung is a rare neoplasm. Here we describe the first report on oncogenes and tumor suppressor genes in metastasizing pleomorphic adenoma of the lung. A 48-year-old Japanese woman presented with metastasizing pleomorphic adenoma in which both the primary lung tumor and metastatic lesions were composed of benign pleomorphic structures. The mechanism of the metastatic potential was examined by analyzing known oncogenes and tumor suppressor genes by DNA blot analysis and immunohistochemistry. No rearrangements amplifications or overexpressions of oncogenes, bcl-2, c-erbB-2, c-myc, L-myc, N-myc, Ha-ras and Ki-ras were found. In addition, immunohistochemical studies showed no aberrance in expressions of the tumor suppressor gene products, RB, p16 and p53 in the tumor. Some unknown mechanism(s) seems to be responsible for the aggressiveness of this metastasizing pleomorphic adenoma. This mechanism must be elucidated by studies on further case of this rare tumor.
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PMID:A case of pleomorphic adenoma of the lung with multiple distant metastases--observations on its oncogene and tumor suppressor gene expression. 967 59

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