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)

Metallothionein (MT) is a low-molecular-weight cysteine-rich protein, which has the ability to bind and sequestrate heavy metal ions. Synthesis of MT is induced in a variety of tissues by these metal ions, as well as by endogenous factors such as glucocorticoids, interferon, interleukin-1 and vitamin D. Several lines of evidence show that MT may play a role in carcinogenesis. In this study MT expression was detected immunohistochemically, using a monoclonal antibody (E9) against a conserved epitope of I and II isoforms, in a series of 63 cases of urothelial carcinomas of the urinary bladder. Correlation between MT expression and HLA-DR antigen expression, p53, proliferation indices (PCNA and MIBI) as well as the various clinicopathological parameters, such as age, sex, squamous metaplasia, tumor grade, stage and recurrence were studied. In a semiquantitative analysis MT expression (> 10% of neoplastic cells) was observed in 12.7%, focal MT positivity in 11.1% and almost completely lack of MT expression in 76.2% of tumors. The incidence of MT expression was significantly higher (p=0.0002) in cases with high pathological tumor grades. MT values were significantly correlated with tumor stage (p=0.0009). A statistically significant positive correlation between MT expression and the HLA-DR antigen expression (p=0.001) was also detected. The data suggested that MT expression was correlated with a more aggressive behavior in urothelial bladder cancer.
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PMID:Localization of metallothionein in urothelial carcinoma of the human urinary bladder: an immunohistochemical study including correlation with HLA-DR antigen, p53, and proliferation indices. 1149 56

Most intraductal papillary-mucinous carcinomas (IPMCs) of the pancreas are resectable and curable, but some develop into frankly invasive carcinomas. We studied the clinicopathologic features of eight cases of invasive carcinoma derived from IPMC (IC-IPMC) of the pancreas. The patients were aged 54-75 years (mean, 66.6 years); six were male and two were female. The mean tumor size was 7.7 cm (range 5.5-10.5 cm). Two patients without lymph node metastasis had no peripancreatic invasion, and survived longer (115 and 20 months). Three out of four patients with extrapancreatic invasion died of their tumors or developed tumor recurrence within a year. One patient with evidence of liver and lymph node metastasis at the time of first surgery again showed metastatic tumor 21 months later. One patient died of another cause. We also performed a comparative study of the immunohistochemical features of IC-IPMCs in 9 IPMCs (including minimally invasive cases) and 15 ductal adenocarcinomas. CEA cytoplasmic positivity was observed in most of the IC-IPMCs (87.5%) and ductal adenocarcinomas (93.3%), but in only 1 IPMC (11.1%). The frequency of p53 nuclear staining in ductal adenocarcinoma (73.3%) was higher than in IPMC (33.3%) or IC-IPMC (37.5%). In conclusion, IC-IPMC with extrapancreatic invasion should be treated as ductal carcinoma because of its aggressive behavior after resection. Some IPMCs might progress to invasive carcinoma via pathways that are different from those followed by ductal adenocarcinomas.
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PMID:Invasive carcinoma derived from intraductal papillary-mucinous carcinoma of the pancreas: clinicopathologic and immunohistochemical study of eight cases. 1149 41

Sarcomatoid renal cell carcinomas (SRC) are rare neoplasms associated with a very poor prognosis. The aim of this study was to evaluate biomarker expression and clinical significance in this uncommon renal cancer. Cytokeratin, epithelial membrane antigen, vimentin, desmin, smooth muscle actin, CD34, S-100 protein, MIB 1, p53, Fas and Fas ligand immunohistochemical expression was investigated in seven renal cell carcinomas with sarcomatoid changes. No significant difference between sarcomatoid and nonsarcomatoid areas was observed with the different biomarkers, excepted for Fas ligand. Fas expression was diffuse in sarcomatoid and nonsarcomatoid areas. However, Fas ligand had a higher expression in sarcomatoid in comparison to nonsarcomatoid areas. Our results showed that Fas and Fas ligand are both expressed in renal cancer. We suggest that the aggressive behavior of sarcomatoid carcinoma may be related to a higher expression of Fas ligand by tumor sarcomatoid cells. These findings may indicate that Fas ligand is a possible therapeutic molecular target for treatment of SRC.
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PMID:Immunohistochemical detection of Fas and Fas ligand in sarcomatoid renal cell carcinoma. 1150 80

Salivary duct carcinoma (SDC) is a rare high-grade aggressive neoplasm that manifests close histologic features with invasive ductal carcinoma of the breast (IDC). In contrast to SDC, extensive molecular studies have been performed on IDC and led to the identification of certain biological markers. To investigate the underlying molecular and biologic characteristics of SDC, we performed molecular analyses using microsatellite markers on chromosomal arms 6q, 16q, 17p, and 17q, DNA flow cytometry and immunohistochemical staining for androgen receptor (AR) and p53 expression on 28 examples of these tumors in comparison to 24 IDC cases. Our results show that generally similar allelic alterations, elevated p53 and androgen receptor expressions, and high frequency of DNA aneuploidy are manifested in both SDCs and IDCs. Differences at certain markers on 6q, 17p and 17q chromosomal loci, however, were observed between the two entities. Certain loci on 6q were more frequently altered in SDC than IDC which loci on chromosomes 17p and q arms were more seen in IDCs than SDCs. The majority of SDCs had high AR expression while most of IDCs were AR negative. Our study indicates that: i) SDC may share some genetic alterations with IDC, ii) high AR expression in SDC may play a role in tumor progression, and iii) p53 overexpression and DNA aneuploidy in both entities reflect their aggressive behavior.
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PMID:Molecular and biomarker analyses of salivary duct carcinomas: comparison with mammary duct carcinoma. 1156 68

Adenocarcinomas arising from adenomyosis uteri are rare. This study reports four such cases and characterizes them clinically and microscopically. In all four patients, the endometrial cytology was negative, and MR imaging and ultrasound sonography did not detect the tumors preoperatively. The histological subtypes of the four tumors were endometrioid (one grade 1, one grade 3), serous, and clear cell. In three cases, the adenocarcinomas were present exclusively in the myometrium, and a transition between the carcinomas and the adenomyotic glands was observed in all cases. The eutopic endometrium was normal except in one case in which there was a small focus of invasive carcinoma. In two of four cases, pelvic or paraaortic lymph node metastases were present. In the carcinomas, ER immunoreactivity was not found in any tumor and PR positivity was found in only one tumor. In contrast, p53 immunopositivity was found in three of four carcinomas. Adenocarcinomas arising from adenomyosis are difficult to diagnose preoperatively, and their aggressive behavior in some cases seems to be related to the histological subtype.
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PMID:Adenocarcinomas arising from uterine adenomyosis: a report of four cases. 1206 69

Molecular analyses of thyroid tumors have documented mutations in the tumor suppressor p53 gene almost exclusively in anaplastic carcinomas. In contrast, immunohistochemistry has localized p53 in differentiated papillary and follicular thyroid cancers. To establish the significance of p53 immunolocalization in these lesions, 78 thyroid tumors of follicular derivation were examined. All tumors were classified by strict criteria and the extent of tumor was determined morphologically. Immunohistochemical staining for p53 was performed on paraffin sections of formalin-fixed tumor tissue. The results of staining were correlated with diagnosis, tumor extent and clinical outcome. Immunopositivity for p53 was diffuse and strong in all five anaplastic carcinomas examined. There was no staining in five of six follicular adenomas. Four of nine follicular carcinomas had some degree of nuclear staining, but this was focal; all nine tumors were confined to the thyroid at the time of examination. Of 49 papillary carcinomas, 26 were intrathyroidal, and 7 of these were occult; there was no p53 positivity in any occult lesion and only S of the 19 palpable lesions stained. In contrast, among 23 papillary carcinomas with extra thyroidal extension or metastases, only 9 were negative for p53 immunoreactivity. Five of seven tall cell papillary carcinomas and one of two insular carcinomas had p53 immunopositivity and this correlated with aggressive behavior. These results support the tumorigenic role of p53 mutations postulated for anaplastic thyroid carcinomas and indicate that localization of p53 by immunohistochemistry is a useful prognostic index of clinical behavior in differentiated thyroid carcinomas of follicular cell derivation.
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PMID:Immunohistochemical Localization of p53 in Human Thyroid Neoplasms: Correlation with Biological Behavior. 1211 68

In predicting the aggressive behavior of bladder tumors, the histopathological characteristics of grade and invasive stage are of principal importance. However, for predicting tumor recurrence and progression, these are sufficient only to a limited extent, particularly in the case of superficial (pTa and pT1) urothelial cell carcinomas. New prognostic factors are therefore needed to avoid either insufficient or excessive treatment. In this retrospective study, we investigated the prognostic value of the p53 and Ki-67 immunoreactivity indices. The present study included 118 superficial urinary bladder tumors consisting of 58 recurrent and 60 non-recurrent cases. Twenty of the recurrent tumors progressed into a higher grade and/or invasive stage. Paraffin immunohistochemical analysis was carried out using anti-p53 and anti-Ki-67 antibodies on the initial tumor tissues. We concluded that there is a highly significant relationship between the p53 and Ki-67 immunoreactivities and the histological grade and pathological stage of the tumors (P < 0.0001). We observed a significant relationship between the presence of recurrence and progression and the p53 immunoreactivity index (P < 0.01 and P = 0.017, respectively) and Ki-67 immunoreactivity index (P < 0.0001 and P = 0.046, respectively). Positivity for p53 and Ki-67 can demonstrate the risk of recurrence (p53: sensitivity = 76%, specificity = 58%; Ki-67: sensitivity = 86%, specificity = 48%) and progression (p53: sensitivity = 80%, specificity = 46%; Ki-67: sensitivity = 85%, specificity = 36%; ). We believe that both of these immunohistochemical markers can be considered valuable in addition to classical histopathological prognostic parameters for predicting recurrence and progression risks.
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PMID:Impact of p53 and Ki-67 in predicting recurrence and progression of superficial (pTa and pT1) urothelial cell carcinomas of urinary bladder. 1216 5

Mutation of the p53 tumor suppressor gene is recognized to be a key event in the development of the highly aggressive behavior of undifferentiated or anaplastic thyroid carcinomas. Attempts to treat these carcinomas with p53 gene therapy have, however, been largely unsuccessful. Since epigenetic changes such as histone deacetylation are associated with loss of thyroid differentiation, we have evaluated the potential of combining p53 gene therapy with exposure to the histone deacetylase inhibitor (HDAC-1), depsipeptide. We used two carcinoma cell lines: FRO cells that express very low levels of p53 and WRO cells producing a dominant negative p53. A p53 response element luciferase assay showed that stimulation of p53 transcriptional activity by the combined treatment with the HDAC-1 and p53 was 10 to 100 times greater than with p53 alone. Western blot analysis demonstrated that the HDAC-1 increased the expression of acetylated histones, as well as of p21(cip1/waf1), but did not affect levels of total histone and endogenous p53. The combined treatment was much more effective than either treatment alone in inhibiting the growth of both cell lines, and flow cytometric analysis suggested that this was due to an increase in the sub-G1 apoptotic population. Our findings indicate that HDAC-1 enhances apoptotic killing by p53 transfer, and suggest that this combination strategy may be useful in treating undifferentiated thyroid carcinomas.
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PMID:A histone deacetylase inhibitor enhances killing of undifferentiated thyroid carcinoma cells by p53 gene therapy. 1236 80

Four cases of brain metastasis from hepatocellular carcinoma (HCC) associated with hepatitis B virus (HBV) are reported in an area not endemic for HBV infection. Two cases are unusual, since cerebral metastases were the only secondary localization. In these cases, no other sites of metastasization were detected either before or immediately following neurosurgical treatment. In all cases the expression of pRB, p53 and p16 tumor suppressor protein was studied with immunohistochemistry, both, in the primary and metastatic lesions. The pRB expression was as follows: in two cases, lack and moderate expression were observed both, in the primary and in the metastases; in the other two, pRB was not detected. In all cases p53 expression was negative both, in the primary and the metastases. P16 expression was moderately expressed in three cases, both in the primary and the metastases. In one case it was absent. Hepatocarcinogenesis is a multistep process, in which several oncogenes and oncosuppressor genes are involved. In four unusual cases of spread to the brain, we evidenced that tumor suppressor protein expression of p16, p53, and particularly pRB (its aberrated expression is usually associated with metastasis) were altered. We also suggest that HBV and its X protein (HBX) might play an important role in such aggressive behavior of the neoplasia.
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PMID:Brain metastasis from hepatocellular carcinoma associated with hepatitis B virus. 1238 72

B-cell chronic lymphocytic leukemia (B-CLL) is a disease with variable course and prognosis. It may be important to predict the possible risk of disease progression in individual patients. We have investigated by immunocytochemistry the bcl-2 and p53 protein expression in 53 B-CLL patients at the time of initial diagnosis. All B-CLL cases were bcl-2 protein positive. The relatively high frequency of p53 protein immunoreactivity was observed (17 of 53 cases; 32%). The percentage of bcl-2 and p53 protein positive cells remarkably varied in individual patients. The heterogeneity in the percentage of bcl-2 as well as p53 positive cells showed to be important in the analysis of mutual relation of these proteins. Noteworthy results were obtained when the group of p53 positive B-CLL patients was analyzed according to the percentage of p53 positive cells (less than 20% and more than 20%, respectively). An inverse relationship between a higher accumulation of p53 and repressed bcl-2 expression and vice versa was observed. The male patients (female patients were not assessed because of the limited number of p53 positive cases) with less than 20% p53 immunoreactive cells revealed a high percentage of bcl-2 protein (p=0.0008). The higher incidence (over 20%) p53 positive cells correlated with lowered percentage of bcl-2 positive cells (p=0.0368). When the patients were subdivided according to p53 positivity and negativity, the majority of p53 positive cases were males (82%), with significantly higher WBC count (p=0.0362). No significant effect of higher or lower WBC counts on bcl-2 and p53 expression was observed. However, the expression of bcl-2 protein was significantly higher in female patients under 50 years (p=0.0012). Regarding the patients of age <or=50 and >50, a significant difference in WBC count was shown in males (p=0.0590). The peripheral blood lymphocytes isolated from healthy subjects used as controls, exhibited undetectable, to low proportion of bcl-2 and p53 positive cells. Comparing the percentage of bcl-2 as well as p53 positive cells in controls and those of B-CLL patients, the significant difference for both proteins was observed (p=0.0009 and p=0.0001, respectively). The results of this study indicate that the overexpression of p53 protein may contribute to the downregulation of bcl-2 in a subgroup of our B-CLL patients. Considering the small numbers of tested p53 positive cases, it would be necessary to confirm our findings in a larger cohort of patients with longer follow up. Thus it would be possible to confirm our expectation of a possible value of the simultaneous aberrant expression of bcl-2 and p53 as useful predictors of future aggressive behavior of B-CLL.
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PMID:Immunocytochemical detection of bcl-2 and p53 proteins in B-chronic lymphocytic leukemia patients. 1258 86

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