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)

Mutations in the TP53 tumor suppressor gene have been studied in different types of brain tumors. Little is known about this genetic event in human meningioma, a mostly benign tumor. To investigate the frequency of TP53 gene mutations in human tumors derived from meningeal tissues, paraffin-embedded tissues from 30 cases (including 2 malignant and 4 atypical meningiomas, as well as 2 hemangioblastomas and 3 hemangiopericytomas) were screened by immunohistochemistry. Polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) and direct DNA sequencing were thereafter performed in selected cases. Nuclear p53 staining was not seen in any of the 19 benign meningiomas tested, while atypical meningiomas, hemangioblastomas, and hemangiopericytomas displayed nuclear staining in a subpopulation of tumor cells in 4 out of 5, 2 out of 2, and 3 out of 3 cases, respectively. One malignant meningioma showed an intense nuclear staining and a band shift in SSCP. In this case, we identified a mutation in the TP53 gene at codon 161 changing GCC to ACC and resulting in an alteration of alanine to threonine in this position. Our results indicate that TP53 gene mutation may be considered as a marker for malignant transformation in meningioma. p53 immunoreactivity, even in the absence of detectable gene mutation, is also associated with atypia and does not appear in regular benign meningiomas.
 ...
PMID:Detection of TP53 gene mutation in human meningiomas: a study using immunohistochemistry, polymerase chain reaction/single-strand conformation polymorphism and DNA sequencing techniques on paraffin-embedded samples. 765 83

Malignant meningiomas are rarely encountered neoplasms. Few studies have examined MIB1 (marker of cell proliferation) or p53 (tumor suppressor gene) immunoreactivity in these tumors. This study retrospectively examines 23 malignant meningiomas (defined by the presence of either unequivocal brain invasion or metastasis) including MIB1 and p53 immunohistochemistry. The patients included 13 women and 10 men who ranged in age from 22 to 82 years (mean 63 years). Initial clinical presentation included weakness or numbness in 10 patients, visual signs or symptoms in 7 patients, and headaches in 6 patients. Histologically, nuclear pleomorphism was present in 23 of 23 tumors, disorganized architecture in 22 of 22, necrosis in 20 of 23, prominent nucleoli in 17 of 23, and hypervascularity in 4 of 23. One to 18 mitotic figures per 10 high power fields (HPF) (mean 6.1) were observed. Metastases were present in six patients (bone: 3 patients; lung: 2 patients; skin: 2 patients; kidney: 1 patient; and liver: 1 patient). MIB1 indices (positive tumor cells per 1,000 tumor cells evaluated x 100) in 20 tumors ranged from 1.3 to 24.2 (mean 11.7). p53 nuclear staining was observed in only 2 of 20 tumors. Follow-up information was available in 21 patients: 6 died of tumor (mean 27 months); 9 are alive with residual tumor (mean 35 months); 5 are alive with no evidence of tumor (mean 12 months); and 1 died 13 days postoperatively. There was no obvious correlation of the MIB1 index and tumor behavior. The majority of malignant meningiomas are characterized by nuclear pleomorphism, architectural disorganization, necrosis, prominent nucleoli, and increased mitoses. MIB1 labeling in most malignant meningiomas was high, consistent with the generally rapid growth of these tumors. Only a rare malignant meningioma demonstrated p53 alteration by immunostaining.
 ...
PMID:Malignant meningioma: a clinicopathologic study of 23 patients including MIB1 and p53 immunohistochemistry. 865 46

The mutations that occur in the p53 tumor suppressor gene have been studied in various human malignant tumors. However, little is known about this gene in meningiomas. To investigate the relationship and frequency of p53 gene mutations, the p53 polymerase chain reaction-single stranded conformational polymorphism (PCR-SSCP) and immunohistochemical study were performed on the 41 intracranial meningiomas (21 benign, 11 atypical, and 9 malignant). The higher the p53 protein expression rate, the poorer the histologic grade (9.5%, 72.7%, and 88.9% in benign, atypical and malignant meningioma, respectively) (p=0.000). The p53 protein expression rate was higher in recurrent meningioma (71.4%) than in nonrecurrent meningioma (10.5%) (p=0.002). PCR-SSCP method was performed in positive p53 protein immunoreactivity cases. p53 gene mutation rate was higher in the atypical (62.5%) and malignant (25%) meningiomas than in the benign meningioma (0%) (p=0.232). Also, the rate was higher in recurrent menigioma (20%) than in nonrecurrent meningioma (0%) (o=0.495). Among five to eight exons of the p53 gene, the mutation was observed on exon 7 more frequently. In conclusion, p53 immunoreactivity and p53 gene mutation are closely correlated with histologic grade and histologic atypia of intracranial meningiomas. p53 gene mutation would be considered as a useful marker to detect the progression of intracranial meningiomas.
 ...
PMID:Role of p53 gene mutation in tumor aggressiveness of intracranial meningiomas. 1033 68

We sought to determine the relative incidence of meningiomas compared to other central nervous system tumours in an Asian surgical series, as well as the demographic and biological characteristics of these meningiomas. A review of 655 consecutive cases of central nervous system tumours from 583 patients representing the last five years admissions to one hospital in Singapore was undertaken. A total of 33 malignant/atypical tumours from 19 patients and 196 benign meningiomas from 187 patients were identified. Twenty malignant/atypical and 20 benign tumours were selected at random and subjected to histochemical and immunohistochemical analysis using antibodies directed against p53, bax and 3'-DNA hydroxy groups (TUNEL). Meningiomas comprised some 35.2% of all central nervous system tumours with malignant/atypical meningiomas representing 9.2% of meningiomas. Histochemically, necrosis was the predominant finding. However, peri-necrotic areas displayed p53 positivity in 10% of cases and bax positivity in 25% of cases. Apoptotic cells were detected in the peri-necrotic areas in 90% of benign and 75% of malignant/atypical meningiomas. Meningiomas represent the predominant form of central nervous system tumour in the Singaporean population, and aberration of p53 expression is not associated with tumour formation or progression. There was a slight but non-significant reduction in apoptosis in the progression from benign to malignant meningioma, suggesting that in contrast to many other tumour types disruption of cellular apoptosis is not a predominant driving force in Asian meningioma tumourigenesis.
 ...
PMID:Meningiomas in Singapore: demographic and biological characteristics. 1098 57

Sclerosing meningioma is a rare morphologic subtype of meningioma and may be mistaken for atypical or malignant meningioma and astrocytoma or schwannoma because of marked collagen deposits and a sparse population of cells with little resemblance to meningothelial cells. Authors describe the histopathologic and immunophenotypic features of five cases of sclerosing meningioma. Histologically, all the cases consisted of paucicellular collagenous tissue containing spindle cells with or without small foci of meningothelial cell proliferation. The morphology and immunohistochemical profile of the spindle cells were different from those of conventional meningothelial cells. The meningothelial cells showed a typical immunoreactivity of conventional meningiomas, while the spindle cells displayed a strong expression of vimentin. The Ki-67 labelling index was uniformly low in all cases, and none of cases expressed p53 protein. In summary, the recognition of meningothelial cells in massively sclerotic lesions is helpful for a correct diagnosis. In the cases with a total absence of meningothelial cells, however, the vague collagenous whorls are more diagnostic rather than immunohistochemistry. Considering association with clear cell meningioma, prospective and retrospective long-term follow-up is necessary for deciding whether reminiscent clear cell meningiomas should be separated from sclerosing meningioma or not.
 ...
PMID:Sclerosing meningioma: immunohistochemical analysis of five cases. 1504 10

Sclerosing meningioma is a distinct histologic subtype of meningioma, however, it is often confused with other tumors, especially malignant tumors. To widen our knowledge of sclerosing meningioma and to help neurosurgeons and neuropathologists diagnose this clinically and pathologically unfamiliar disease entity, we reviewed four such cases, which were originally misdiagnosed. Sclerosing meningiomas were assessed for cellularity, cellular pleomorphism, mitotic activity, brain invasion, and necrosis. Immunohistochemical staining was performed on paraffin-embedded sections using the avidin-biotin-peroxidase complex method. The histologic appearance of the underlying cerebral parenchyma invasion by tumor cells led to a diagnosis of malignant meningioma or to the completely erroneous diagnosis of ganglioglioma. The most conspicuous histologic finding of these four sclerosing meningiomas was extensive collagen deposition, so called 'sclerosis' and an intermingled small population of spindle or round cells with clear cytoplasmic halos, giving a 'fried egg' appearance. However, a typical meningothelial whorl pattern was identified in all cases. Tumor cells exhibited positive immunoreactivity for epithelial membrane antigen and vimentin, but were negative for glial fibrillary acidic protein, p53, S-100, and neuronal markers. Proliferative indices, using Ki-67, ranged from 0% to 4%, and brain invasion was present in three of four tumors. All four patients are doing well with no evidence of tumor recurrence (follow-up duration of 25 months to 12 years). Brain invasion needs to be re-evaluated as a criterion of malignancy in meningioma. Special attention should be paid to the diagnosis of this subtype of meningioma to prevent unnecessary postoperative radiotherapy and to ensure correct therapeutic decision.
 ...
PMID:Sclerosing meningioma: clinicopathological study of four cases. 1521 54

Patients with Neurofibromatosis type 1 (NF1) and Neurofibromatosis type 2 (NF2) are predisposed to tumors of the nervous system. NF1 patients predominantly develop neurofibromas, and Malignant Peripheral Nerve Sheath Tumors (MPNST) while NF2 patients develop schwannomas and meningiomas. Here we quantified the drug sensitivities of NF1 and NF2 tumor cell lines in a high throughput platform. The platform contained a comprehensive collection of inhibitors of MEK, RAF, RAS, farnesyl transferase, PAK and ERK, representative drugs against many other cancer pathways including Wnt, Hedgehog, p53, EGF, HDAC, as well as classical cytotoxic agents recommended for treating MPNST, such as doxorubicin and etoposide. We profiled seven NF1-associated MPNST cell lines (ST88-14, ST88-3, 90-8, sNF02.2, T265, S462TY, SNF96.2), one sporadic MPNST cell line (STS26), one schwannoma from a NF2 patient (HEI193), one NF2-deficient malignant meningioma (KT21-MG-Luc5D), one mouse NF2 schwannoma (SC4) and one sporadic rat schwannoma (RT4-67 or RT4). NF1 cells were primarily distinguished from NF2 cells and the sporadic MPNST cell line by their sensitivity to MEK and ERK inhibitors, and to a smaller extent their sensitivity to BH3 mimetics and farnesyl transferase inhibitors. The platform was highly successful in predicting the effects of clinical trials for Neurofibromas.
 ...
PMID:Comprehensive pharmacological profiling of neurofibromatosis cell lines. 2846 64