UNIPROT:P04637 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Some investigators have reported that the histological features of osteosarcoma (OS) arising in elderly patients are different from those in younger patients; however, a molecular biologic study of OS in elderly patients has not been documented. In this study, 23 cases of OS (15 osteoblastic and 8 MFH-like types) and 18 cases of MFH of bone in patients 40 years of age or older were analyzed for mutation of the p53 gene, amplification of the MDM2 gene, and mutation of the H-ras gene, using formalin-fixed paraffin-embedded materials. We also examined the expression of p53, MDM2, and p21WAF1 protein immunohistochemically and assessed the proliferative activities using the monoclonal antibody MIB-1. p53 immunoreactivity was recognized in 5 of 23 OS cases (22%), whereas p53 gene mutations were also detected in 5 of 23 OS cases (22%; osteoblastic [4/15; 27%] and MFH-like [1/8; 18%] types) and in 4 of 18 cases of MFH of bone (22%). There was a statistically significant correlation between p53 immunoreactivity and p53 mutation status in OS (P =.0482). All those cases of osteoblastic OS and MFH of bone that had p53 mutations, with the exception of one case of MFH of bone that had a silent mutation, showed aggressive biologic behavior (dead of disease within 12 mo), in contrast to the MFH-like OS cases (alive without disease at 22 mo). Three cases of OS (13%) and three cases of MFH of bone (17%) showed immunoreactivity for MDM2. As for gene alteration, three cases of OS (13%) and 3 cases of MFH of bone (17%) demonstrated MDM2 amplification. MDM2 amplification showed a significant correlation with the expression of MDM2 protein in OS (P =.0344). p21WAF1 expression was detected in three cases of OS (13%) and in six cases of MFH of bone (33%). MDM2 alteration and p21WAF1 expression were not observed in any of the cases of MFH-like OS. MIB-1-LI showed a statistically significant correlation with p53 immunoreactivity and MDM2 immunoreactivity in OS (P =.0307 and P =.0358, respectively). H-ras mutation at Codons 12 and 13 was not recognized in any of the cases of OS or MFH of bone. In conclusion, although treatment differences during the time of study make it difficult to compare survival analysis, in the current study, p53 mutation in osteoblastic OS and MFH of bone in elderly patients seemed to be closely associated with the progression of the tumor, which was not the case in MFH-like OS. Furthermore, MDM2 alteration and p21WAF1 expression were demonstrated only in osteoblastic OS and MFH of bone, whereas they were not recognized in MFH-like OS. Although the number of patients in this analysis was small, it would appear that MFH-like OS may have some characteristic biologic aspects when compared with osteoblastic OS and MFH of bone in elderly patients.
...
PMID:Molecular analysis of p53, MDM2, and H-ras genes in osteosarcoma and malignant fibrous histiocytoma of bone in patients older than 40 years. 1218 Dec 74

A number of human cell lines derived from well-differentiated, myxoid/round cell, or pleomorphic liposarcoma have been described. To our knowledge, however, no human cell line established from dedifferentiated liposarcoma has been reported. In this study, we established a new human cell line, FU-DDLS-1, which originated from a dedifferentiated liposarcoma arising in the retroperitoneum of a 61-year-old man. This cell line was characterized by immunocytochemistry, conventional banding analysis, fluorescence in situ hybridization with chromosome painting probe, and comparative genomic hybridization (CGH). FU-DDLS-1 cells were spindle or polygonal shaped and possessed oval nuclei and slender cytoplasmic processes. The cultured cells were successfully maintained in vitro for over 90 passages over more than 30 months. The histologic features of heterotransplanted tumors in severe combined immunodeficiency mice were essentially the same as those of the original nonlipogenic sarcoma resembling a malignant fibrous histiocytoma. Both in vitro and in vivo, the cells exhibited immunopositive reaction for mdm2 and p53 proteins. Cytogenetically, FU-DDLS-1 displayed a hypertetraploid karyotype with giant marker chromosomes composed partly of chromosome 12 material. In addition, CGH analysis demonstrated that DNA sequence copy number changes including a gain of 12q12-q21 detected in FU-DDLS-1 were essentially the same as those in the original sarcoma. The FU-DDLS-1 cell line, which exhibits the unique conventional and molecular cytogenetic characteristics of dedifferentiated liposarcoma, should be a particularly useful model for studying the molecular pathogenesis of human dedifferentiated liposarcoma.
...
PMID:Establishment of a novel human dedifferentiated liposarcoma cell line, FU-DDLS-1: conventional and molecular cytogenetic characterization. 1257 6

A case of cutaneous atypical fibroxanthoma (AFX) which metastasized, leading to patient death, is described. This is the third reported case in which a lesion qualified as AFX behaves in such an aggressive manner, comparable with that of malignant fibrous histiocytoma (MFH). Ki-67 proliferation index, p53 and bcl-2 protein expression and DNA ploidy were also consistent with a highly malignant potential. The controversial issue of the biological behavior of AFX and its relationship with MFH is discussed. The authors conclude that MFH and AFX probably represent a single entity with a split biological "personality".
...
PMID:Atypical fibroxanthoma and malignant fibrous histiocytoma of the skin. 1282 Apr 68

We report the clinicopathologic findings of four cases of liposarcoma with meningothelial-like whorls. Two cases occurred in the retroperitoneum and the remaining cases in the anterior mediastinum and scrotum. The whorls varied in terms of amount and morphology and the type tissue surrounding the whorls also varied in every case. One of the retroperitoneal cases with large areas of whorl coalescence recurred in the abdominal wall as an inflammatory malignant fibrous histiocytoma one year after primary resection of the tumor, and a metastasis to the cervical spines was detected twenty months later. The other retroperitoneal tumor recurred locally two years after the resection of the tumor and the amount and cellularity of the whorls as well as p53 reactivity and Ki-67 labeling index were higher in the recurrent tumor. However, coalescence of the whorls was not present in the recurrent tumor in contrast to the primary tumor. The anterior mediastinal and scrotal cases have demonstrated neither local recurrence nor distant metastasis although the follow-up period has been less than one year. The cells comprising whorls showed positive reactions for CD10, CD56, CD99, factor XIII, and low-affinity nerve growth factor receptor in addition to vimentin and alpha-smooth muscle actin. Our results indicate that liposarcoma with meningothelial-like whorls is a heterogeneous group that shows wide variations in histologic findings and biologic behavior. The phenotypic transformation of the whorls to higher grade in two retroperitoneal tumors, which showed recurrence within two years of follow up, supports that a whorl is a sign of dedifferentiation. Although we demonstrate the expressions of several markers, such as CD10, CD56, CD99, factor XIII, and low-affinity nerve growth factor receptor, in the spindle cells of the whorls for the first time, the lineage of the whorls still cannot be addressed due to the fact that these markers are lineage nonspecific.
...
PMID:Liposarcoma with meningothelial-like whorls. Report of four cases showing diverse histologic findings and behavior. 1283 76

Malignant fibrous histiocytoma (MFH) is a rare primary neoplasm that constitutes less than 1% of the malignant tumors of bone, and involvement of the skull is very rare. We present a case of malignant fibrous histiocytoma of the skull, presenting an intraosseous lesion in a 43-yr-old woman. She had a rapidly growing, tender mass in the right parietal region. A plain radiograph showed an osteolytic lesion of the right parietal bone. Magnetic resonance imaging revealed that the lesion showed heterogeneous low signal intensity on T1-weighted images and slightly high signal intensity on T2-weighted images. No evidence of an extraosseous extension to the adjacent dura and soft tissue was found, and a wide excision of the parietal bone was performed. Histologically, the tumor was a typical MFH displaying pleomorphic spindle cells in a storiform pattern. The results of immunohistochemical stainings revealed that the tumor cells were positive for vimentin, alpha-1-antitrypsin, and p53, and negative for smooth muscle actin, S100 protein, desmin, and MyoD1. Three months later, a mainly cystic, recurrent mass was developed at the previously operated site. Before the resection, we first performed the percutaneous aspiration cytology, revealing diagnostic multinucleated pleomorphic cells. Thereafter, she had to receive repetitive resections of recurrent or residual lesions, and she died of postoperative meningoencephalitis two years after the first operation.
...
PMID:Primary intraosseous malignant fibrous histiocytoma of the skull: a case report. 1292 45

Like malignant fibrous histiocytoma (MFH), dedifferentiated liposarcoma represents a distinct subtype of liposarcoma and is characterized by an abrupt transition from well-differentiated liposarcoma (WDL) to highgrade dedifferentiated liposarcoma (DDL) . In addition, specific cytogenetic aberrations support the close biological relationship between WDL and DDL. Recent observations indicated the significance of cell cycle aberrations in tumor progression from the low-malignant, well differentiated to its dedifferentiated form, the prognosis of which is poor. Thus, alterations of mdm2 and p53 genes belong to the most frequently reported alterations in these two subtypes of liposarcoma. In previous investigations, we reported that loss of heterozygosity at the Rb gene locus, telomerase activity, hTERT, and c-Myc expression were associated with tumor progression in liposarcomas. In this study, we report on a case of a WD/DDL, in which both tumor components were separated using laser microdissection (P.A.L.M.) for the investigation of hTERT mRNA expression on a LightCycler. Macroscopically selected and histologically proven cryosections of low malignant and highly malignant tumor areas were cytogenetically investigated to confirm the diagnosis and to find additional chromosomal alterations with tumor progression.
...
PMID:Different mRNA expression profile during tumor progression in a well-differentiated liposarcoma--A microdissection approach. 1292 48

Myxofibrosarcoma/myxoid malignant fibrous histiocytoma (MFH) has continued to be considered a distinct entity even after recently published reassessments of pleomorphic sarcomas and MFH. Several cell cycle-regulated proteins have already been screened by immunohistochemistry with the aim of finding the reliable prognostic indicator of soft tissue sarcomas; however, it is still unknown whether their altered expression affects patient survival in myxofibrosarcoma. In this study, we evaluated the expression of p53, MDM2, MIB-1 (Ki-67), p21, p27, p16, cyclin A, cyclin D1, and cyclin E by immunohistochemistry in 45 cases of myxofibrosarcoma. First, we searched for possible clinicopathologic prognostic factors in 61 cases of myxofibrosarcoma for which follow-up data were available. In univariate analysis, large tumor size (> or =5 cm), deeply situated tumor, and high histological grade (grade 2 or 3) significantly decreased survival (log-rank test, P <0.05). Among 43 cases of myxofibrosarcoma for which immunohistochemical findings were available, high MIB-1 labeling index (LI) (cutoffs of 10 and 22.5 on average), high cyclin A LI (cutoffs 10% and 13.8% on average), low p21 LI (cutoffs 10 and 20.7 on average), and reduced abnormal expression of p16 were adverse prognostic factors. In multivariate analysis (Cox proportional hazards model), high mitotic rate (>15/10 high-power fields), p53 immunoreactivity (cutoff 10%), high MIB-1 LI (>22.5), low p21 LI (<20.7), and low p27 LI (<47.8 on average) were independent poor prognostic factors. Our results suggest that reduced expression of p21 could be considered a new parameter to be evaluated, along with classical clinicopathologic prognostic factors, for identifying those at high risk for myxofibrosarcoma.
...
PMID:Altered expression of cell cycle regulators in myxofibrosarcoma, with special emphasis on their prognostic implications. 1460 38

We observed three neoplasms with completely different histologies: malignant fibrous histiocytoma (MFH), atypical meningioma (AM), and glioblastoma (GB), developing in a patient with Li-Fraumeni syndrome. By using a combined molecular approach we performed molecular characterization of all three tumours. Data obtained showed an interesting molecular background of the AM and GB. AM showed TP53mutations and a 22q loss of heterozygosity (LOH). GB showed epidermal growth factor receptor (EGFR) amplification and TP53 mutations, whereas P16, PTEN, Rbwere intact in terms of LOH and/or multiplex PCR (polymerase chain reaction) analysis. Additionally, GB has a 1q LOH, which is an extremely rare alteration in glioblastomas. Identical 1q LOH was also observed in MFH.
...
PMID:Atypical molecular background of glioblastoma and meningioma developed in a patient with Li-Fraumeni syndrome. 1571 70

Soft tissue sarcomas frequently carry p53 mutations reducing chemotherapeutical response. Especially malignant fibrous histiocytoma (MFH) reveals a reduced ifosfamide (IF) chemosensitivity when compared to other sarcoma entities. This is the first study to analyze MFH cells for the effects of IF on the expression of the pathways P16-CDK4-Rb and P14ARF-MDM2-P73 regulating cell cycle. The aim was to identify candidate genes possibly involved in the anti-apoptotic response of p53-deficient MFH cells during chemotherapy. PCR, real-time RT-PCR and confocal laser scanning microscopy were applied on primary cultures of MFH cells containing defective p53 genes. The cultures were treated with different concentrations of IF. A non-treated MFH culture served as negative control. A threshold concentration of IF (100 microM) was determined sparing the majority of the cells (99%), whereas higher IF quantities caused complete apoptosis. Data collected over a period of 48 h showed that the MFH cells surviving 100 microM IF overexpressed the kinase gene CDK4 and oncogene MDM2 by a factor of 63. A similar strong increase was observed at the protein level for both proteins. In contrast, the other proteins analyzed were not detectable. Additionally, the MFH cells induced complex patterns of MDM2 mRNA splicing and an abnormal mRNA transcript carrying a novel MDM2 missense mutation. These effects were neither observed in the non-treated culture nor in cultures completely inducing spontaneous apoptosis. Therefore, we speculate that the induction of the gene CDK4, and especially of MDM2, is involved in anti-apoptotic mechanisms of p53-negative MFH cells tolerating IF in vitro. Further experiments are necessary to test whether the novel candidate genes favor development of chemoresistance and whether MDM2 mRNA splicing variants contribute to this process in vivo.
...
PMID:Analysis of central regulatory pathways in p53-deficient primary cultures of malignant fibrous histiocytoma exposed to ifosfamide. 1573 17

The term malignant fibrous histiocytoma (MFH) is widely used for pleomorphic soft tissue sarcomas without a specific line of differentiation. MFH is included in the category of fibrohistiocytic soft tissue tumors. MFH has a broad range of histological appearances, and it has several subtypes. All of these subtypes are composed of spindled fibroblast-like cells, undifferentiated cells, and histiocytic or histiocyte-like cells. A large number of fibroblast-like and pleomorphic cells express factor XIIIa in MFH. The cytological pleomorphism of factor XIIIa cells suggests that these cells may belong to the neoplastic population. It is equally possible that the factor XIIIa-positive cells are only activated stromal cells. The relation of factor XIIIa-positive cells to the neoplastic cell population in MFH is addressed in the present study. A morphometric approach compares the measure of nuclear pleomorphism of the factor XIIIa-positive cells with that of the factor XIIIa-negative tumor cells in high-grade MFH. The immunohistochemical approach compares the factor XIIIa-positive and -negative cell populations with regard to mutations of p53 tumor suppressor gene in p53-positive MFH cases. We selected 58 cases of soft tissue pleomorphic or storiform-pleomorphic MFH on the basis of histopathological examinations. A combination of incident light immunofluorescence for factor XIIIa and transmitted light examination for nuclear staining was used for morphometrical analysis. We found cytoplasmic factor XIIIa positivity in at least 2% of cells in 39 cases; the number of factor XIIIa-positive cells was under 0.5% in two cases, and the number of factor-positive cells ranged between 0.5% and 2% in 13 cases. Eighteen cases were analyzed with nuclear morphometry. We found that mean nuclear area and mean nuclear Ferret diameter in factor XIIIa-positive cells differed significantly from those of the tumor cells in all cases. The mean nuclear roundness factor differed significantly only in four cases. The latter finding showed that the microscopic polymorphism of factor XIIIa cells is measurable and is not merely a suspicion. The immunohistochemical positivity for p53 positivity can be accepted as the manifestation of a missense mutation of TP53 gene and as a marker of neoplastic cells. The simultaneous immunohistochemical detection of factor XIIIa and p53 in the same section revealed that factor XIIIa-positive cells were invariably p53 negative in MFH. This finding implies that the factor XIIIa cell population is non-neoplastic and belongs to the stromal component of MFH.
...
PMID:Histiocyte-like cells expressing factor XIIIa do not belong to the neoplastic cell population in malignant fibrous histiocytoma. 1604 46

<< Previous 1 2 3 4 5 6 7 Next >>