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)

Amplification of 12q13-14 occurs in a subset of human sarcomas including malignant fibrous histiocytoma and liposarcoma. This chromosomal region has previously been found to include a number of growth-related genes including the GLI proto-oncogene and the p53-associated protein, MDM2. We now report the characterization of SAS (sarcoma amplified sequence), a novel transcript found in this region. Sequence analysis demonstrates that SAS is a novel member of a transmembrane protein family (transmembrane 4 superfamily or TM4SF) thought to be involved in growth-related cellular processes. This observation adds a TM4SF protein to the cluster of genes at 12q13-14 frequently amplified in human sarcomas.
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PMID:SAS, a gene amplified in human sarcomas, encodes a new member of the transmembrane 4 superfamily of proteins. 813 23

Mutations in the p53 tumor suppressor gene occur in > 50% of human malignancies, but are exceedingly rare in benign tumors. The malignant potential of fibrous tumors of children may be unpredictable at microscopic examination. We therefore sought to determine whether malignant fibrous tumors could be distinguished from their benign counterparts by the presence of mutations in p53. We screened 27 fibrous tumor samples from 20 young patients. Tumors were classified as benign, borderline, or malignant by conventional microscopic criteria. RNA extracted from each specimen was used as the template for reverse transcription followed by polymerase chain reaction (PCR) amplification, with six pairs of primers covering the whole coding region of the p53 gene. All PCR products were screened for the presence of mutations using single-strand conformation polymorphism analysis. In addition, PCR products encompassing exons 5-9, the sites of the most frequent mutations in human tumors, were sequenced directly. Both methods detected a single point mutation in a highly malignant tumor (malignant fibrous histiocytoma). The mutation was a silent one at codon 36 (CCG-CCA, Pro-Pro). We conclude that p53 mutations are infrequent in childhood fibrous tumors, consistent with previous observations of low malignant potential (< 10%) and better prognosis in this tumor group. Therefore, screening for p53 mutations is not a useful prognostic indicator in fibrous tumors with borderline pattern at microscopic examination.
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PMID:Infrequent mutation of the p53 gene in fibrous tumors of infancy and childhood. 828 21

Alterations of tumour suppressor genes are considered crucial steps in the development of human cancers. Expressions of p53 protein, a product of the tumour suppressor gene altered most commonly in human cancers examined so far, were investigated immunohistochemically in 18 osteosarcomas and 40 other malignant and benign lesions of bone. A monoclonal antibody clone PAb240, which recognizes a common conformational epitope of mutant p53 proteins, stained nuclei of tumour cells in 12 of 18 osteosarcomas (67%). Six tumours (33%) particularly showed positive immunoreactions in more than half of the tumour cells. PAb240 also stained tumour cells in a small number of other malignant bone tumours, such as malignant fibrous histiocytoma, chondrosarcoma, and Ewing's sarcomas. Furthermore, a small number of cells of giant-cell tumours were positively stained. In contrast, PAb240 was completely negative in 21 benign bone tumours and reactive lesions examined. Another monoclonal antibody clone PAb1801, which reacts with both wild- and mutant-type p53 protein, reacted in nuclei of tumour cells of 7 osteosarcomas (39%). Most of those also reacted with PAb240. PAb1801 was expressed much more frequently in other malignant bone tumours and giant-cell tumours. In addition, PAb1801 showed intranuclear positive reactions in tumour cells of a benign chondroblastoma, and reactive cells such as actively proliferating preosteoblasts in a myositis ossificans and osteoclast-like giant cells in a giant-cell tumour. The immunoelectron-microscopic observation that p53 protein was localized in euchromatic areas of nuclei of osteosarcoma cells supported the specificity of immunoreaction for p53 protein, indicating an active role of p53 protein in the regulation of DNA synthesis and transcription. These findings suggest that point mutation of the p53 gene is frequently involved in the development of osteosarcomas. PAb240 may be a useful tool not only in screening point mutations of the p53 gene in osteosarcomas but also in the differential diagnosis between osteosarcomas and reactive bone-forming lesions. Expressions of mutant p53 protein were not correlated with any clinical or pathological factors examined, although the results should be confirmed in studies of a large number of osteosarcomas.
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PMID:Analysis of mutant P53 protein in osteosarcomas and other malignant and benign lesions of bone. 841 91

We report a constitutional mutation of codon 273 in exon 8 of the p53 gene. The affected individual has developed multiple independent benign and malignant tumours (tricholemmoma of the scalp, multiple trichoepitheliomata of the face, osteosarcoma of the ovary, bilateral breast cancer, malignant fibrous histiocytoma of the thigh and endometrial adenocarcinoma) and belongs to a family with some, but not all, features of the Li-Fraumeni syndrome. The mutation, found in both blood lymphocyte and tumour specimens, is a cytosine to thymine transition at codon 273, resulting in an amino acid change from arginine to cysteine. The mother and sister of the index case both died of tumours at an early age. We have demonstrated that formalin-preserved material from these tumours contains the same C-->T mutation at codon 273, indicating that this mutation has probably been transmitted through the germline. All tumours from the index case, both benign and malignant, showed immunohistochemical positivity with four antibodies to the p53 protein. Positive staining was also seen in scattered nuclei of morphologically normal epidermal keratinocytes and pilosebaceous cells, but not in lymphocytes or other morphologically normal cells from the index case. However, a similar staining pattern in apparently normal tissue was also observed in 13/48 sections from other individuals with various skin conditions (melanocytic naevi, psoriasis and normal skin adjacent to malignant melanoma and fibrous histiocytomas), suggesting that this pattern of p53 staining may not be unique to individuals with constitutional p53 mutations.
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PMID:Constitutional mutation in exon 8 of the p53 gene in a patient with multiple primary tumours: molecular and immunohistochemical findings. 847 49

A case of a 54-year-old woman is described who developed synchronously two malignant bone tumors: a dedifferentiated chondrosarcoma in the olecranon and a malignant fibrous histiocytoma (MFH) in the lower tibia. The anaplastic part of the dedifferentiated chondrosarcoma revealed an MFH-like pattern. Myogenous differentiations were not observed in the anaplastic sarcoma cells. The MFH in the tibia showed a storiform-pleomorphic pattern. Single tumor cells showed positivity for M-actin and desmin pointing to myogenous differentiation. DNA-cytophotometry of the dedifferentiated chondrosarcoma showed an aneuploid stem cell line. The MFH in the tibia did not reveal aneuploid stem cells. Staining for p53 protein was negative in both tumors. SSCP analysis and sequencing of the p53 gene in both tumors revealed in the dedifferentiated chondrosarcoma a mutation in exon-8 with the transversion from G to T in codon 294 resulting in a substitution of a stop codon for GLU. The mutation was not observed in the MFH. From these immunohistologic, DNA-cytometric and molecular biologic investigations, we consider it probable that the tumor in the lower tibia is a second highly malignant bone tumor and not the metastasis of the dedifferentiated portion of the dedifferentiated chondrosarcoma in the olecranon.
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PMID:Synchronous multifocal bone sarcomas--a case report and molecular pathologic investigation. 854 10

Silver staining PCR-SSCP method was used to detect point mutation of p53 gene in paraffin-embedded malignant fibrous histiocytoma (MFH) tissues. The abnormal shifting of the single-stranded DNA (ssDNA) was identified in 9 out of 16 cases. The positive figure of SSCP was 1,4,4, 3 in exon 5, 6, 7, 8, respectively. The mutant p53 protein was detected by microwave oven treatment and ABC immunohistochemistry. Positive nuclear staining was observed in 10 cases. The positive coincidence rate was 90.0% between SSCP and p53 protein expression. The mutation of p53 gene was not correlated with the subtypes of MFH. Our results indicate that detection of point mutations with silver staining PCR-SSCP is convenient, rapid and reliable in the screening of point mutation of genes.
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PMID:[Detection of point mutation of p53 gene by silver staining PCR-SSCP in paraffin-embedded malignant fibrous histiocytoma]. 873 3

An immunohistochemical method utilizing microwave oven treated avidin-biotin complex (ABC) technique was used in this study to detect P53 protein expression in 87 parafin-embedded fibrous neoplasm tissues. The results showed that the total positive staining rate was 20.7%. The positive staining rate in fibroma (FA), dermatofibrosarcoma protuberans (DFSP) fibrosarcoma (FS) and malignant fibrous histiocytoma (MFH) were 0%, 4.0%, 37.5% and 62.5% respectively. The positive staining rate of P53 protein was increased with the increase in malignancy of the neoplasma. The expression of P53 protein was not correlated with the subtypes of DFSP and MFH, but correlated with cell differentiation. Therefore, detection of P53 protein expression may have significant value in the evaluation of malignancy, metastatic potential and the prognosis of fibrous neoplasma.
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PMID:[A study of P53 protein expression in fibrous neoplasms]. 876 31

Fifty-two cases of malignant fibrous histiocytoma (MFH) were evaluated for amplification of the MDM2 gene, mutation of the P53 gene, accumulation of the P53 gene product, and their relation to disease-free and overall survival. All tests were carried out on formalin-fixed, paraffin-embedded tissue samples. Amplification of the MDM2 gene was detected in 15 of 52 cases (29%). Six of 52 cases (12%) demonstrated abnormalities of the P53 gene. Sequence analysis detected point mutations in four cases and a 1-base pair deletion in one case, whereas differential polymerase chain reaction (dPCR) indicated that the P53 gene had been entirely deleted in one case. Eight of 52 cases (15%) demonstrated staining for the P53 protein in >10% of tumor cells. The presence of MDM2 amplification did not have a significant effect on either disease-free or overall survival. Patients with accumulation of the P53 gene product did not differ in disease-free or overall survival from patients without P53 accumulation. Survival also was not significantly different in patients with genetic aberration in P53. However, when the patients were stratified by histologic grade, the results indicated that patients with alterations in the P53 gene may have shorter overall survival.
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PMID:MDM2 amplification, P53 mutation, and accumulation of the P53 gene product in malignant fibrous histiocytoma. 891 47

Dedifferentiated liposarcoma represents a distinct subtype of liposarcoma and is characterized by the presence of abrupt transition from well-differentiated liposarcoma to high-grade pleomorphic sarcoma (mostly MFH-like). A key role for p53 in tumour progression of this subset of liposarcomas has been suggested on the basis of p53 immunopositivity. A series of 14 dedifferentiated liposarcomas has been investigated by analysing the p53 gene and protein together with the p53-related molecules p21Waf1 and mdm2, to verify whether the p53 pathway is involved in the development and progression of this tumour type. The results indicate that the p53 gene is rarely involved in dedifferentiated liposarcoma (7 per cent of cases analysed) and that low percentages of p53 immunopositivity are still compatible with integrity of the p53 gene. This concept is also supported by the observed preservation of p21Waf1 immunoreactivity in all but the p53-mutated cases. By contrast, mdm2 overexpression emerges as the most frequent abnormality in dedifferentiated liposarcoma (57 and 78 per cent of cases in well-differentiated and high-grade areas, respectively).
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PMID:Molecular abnormalities of the p53 pathway in dedifferentiated liposarcoma. 907 97

Information on prognostic factors is essential to establish appropriate therapeutic modalities for soft tissue sarcoma (STS). To evaluate the biological nature and prognostic factors of STS, p53 and bcl-2 expression was immunohistochemically studied on paraffin-embedded sections from 70 patients with STS in the extremities and trunk. In addition, the degree of apoptosis was examined by in situ end-labeling. Histologic diagnoses in these cases were malignant fibrous histiocytoma in 29 cases, liposarcoma in 11, synovial sarcoma in 11, leiomyosarcoma in 5, malignant neurogenic tumor in 5, and others in 9. Tumor cells in 31 of 70 cases (44%) showed positive nuclear staining for p53 protein. There was no correlation between p53 expression and tumor size, histologic grade, argyrophilic nucleolar organizer region (AgNOR) count, cellularity and extent of neerosis. Expression of p53 did not correlate with survival of patients. Tumor cells in 24 of 56 cases (43%) were positive for bcl-2 protein expression. The frequency of bcl-2 expression in the tumor cells showed a direct proportion to tumor size (> or = 10 vs. < 10 cm) but inverse proportion to AgNOR counts and cellularity. The 5-year survival rate in patients with bcl-2-positive tumors (87%) was more favorable than in those with bcl-2-negative tumors (53%; p < 0.05). The frequency of apoptosis in low-grade STS was significantly higher than that in the intermediate and high-grade STS (p < 0.001). Extent of necrosis, a well-known prognostic indicator in STS, was not correlated with the frequency of apoptosis. Multivariate analysis showed that cellularity, bcl-2 and AgNOR counts were independent prognostic factors in patients with STS. The current study revealed that STS with a higher expression of bcl-2 had lower proliferative activity and larger size than those without. Immunohistochemical detection of bcl-2 is useful for predicting prognosis in patients with STS.
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PMID:Immunohistochemical detection of bcl-2 and p53 proteins and apoptosis in soft tissue sarcoma: their correlations with prognosis. 914 6


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