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)

To examine the differentiation and proliferative activity of tumor cells, 30 osteosarcomas, including osteoblastic, chondroblastic, fibroblastic, malignant fibrous histiocytoma-like, telangiectatic, giant cell-rich low-grade central, and epithelioid types, were studied immunohistochemically. A variable number of tumor cells in all cases showed osteocalcin immunoreactivity. In four preparations of the frozen sections, osteoblastic, fibroblastic, and chondroblastic tumor cells were positive for bone-type alkaline phosphatase antibody 2D3. S-100 protein immunoreactivity was found not only in seven tumors of the chondroblastic type, but also in four of nine osteoblastic tumors and each of the low-grade central, giant cell-rich, and epithelioid types. A histiocytic marker, CD68, was negative for tumor cells in all cases. Some cells of 17 tumors were positive for desmin and/or alpha-smooth muscle actin; this was regarded as an indication of myofibroblastic differentiation. Tumor cells of the epithelioid type and those of two osteoblastic tumors expressed cytokeratin (CAM5.2) and epithelial membrane antigen. Proliferating-cell nuclear antigen (PCNA) reactivity was found in the cell nuclei of 22 tumors, most of which were high grade. Many cells in six high-grade tumors also showed the nuclear staining for p53 protein. Of these tumors, PCNA and p53 positivities tended to be more numerous in osteoblastic cells, atypical spindle-shaped, and bizarre giant cells than in well-developed chondroid cells. From these findings, osteosarcomas are concluded to be composed basically of osteoblastic cells, that are indispensable for diagnosis of osteosarcomas, with a variable number of chondroblastic, myofibroblastic, and, rarely, epithelioid cells, and this manifold cellular differentiation corresponds to the histological and clinical diversities. The osteoblastic, fibro- or myofibroblastic, and undifferentiated cells mainly participate in proliferation of osteosarcomas. The p53 gene alterations may play a part in the neoplastic transformation and proliferation of osteosarcomas.
 ...
PMID:Histological and immunohistochemical diversities, and proliferative activity and grading in osteosarcomas. 916 46

Three rare cases of familial aggregation of soft tissue sarcomas (malignant fibrous histiocytoma in a mother and liposarcomas in her two children) are described. The mother developed a late onset of malignant fibrous histiocytoma in her right thigh. Her son and daughter both developed retroperitoneal liposarcomas at the ages of 38 and 33 years, respectively. The mother also developed gastric carcinoma as a second malignancy after a 2-year interval. These clinical features closely resemble those of Li-Fraumeni syndrome, but do not fulfill the exact diagnostic criteria. Genetically, the germline mutation of the p53 gene between exons 4 and 9 was not detected by sequencing DNA obtained from the peripheral blood of the mother. Immunohistochemically, p53 protein was found only in the liposarcoma of the daughter. These results strongly suggest that this familial aggregation of soft tissue sarcomas is very rare, and that it is a unique feature of a familial cancer syndrome that to our knowledge has not been defined or described previously.
 ...
PMID:Familial aggregation of soft tissue sarcomas: a report of three cases from a Li-Fraumeni-like family. 916 3

Explanations for the disparate behavior of atypical fibroxanthoma (AFX) as compared with pleomorphic malignant fibrous histiocytoma (MFH) have included the proposition that the former is a pseudosarcoma. Nonetheless, these tumors are now widely regarded as the same process, but with AFX behaving benignly by virtue of its superficial location. However, a neoplasm's metastastatic potential has been proposed to be related to apoptosis. Therefore, the aim of the present study was to examine apoptotic counts, in conjunction with two important regulators of apoptosis: p53 and bcl-2, to determine if a distinction exists that may account for the different outcomes of these lesions. There was no significant statistical difference between eight AFX and nine pleomorphic MFH in terms of apoptotic behavior, proliferative indexes, p53 protein expression, or presence of bcl-2 product. Therefore, our results further support the contention that AFX should be regarded as a form of pleomorphic MFH, which demonstrates low malignant potential by virtue of its location in readily accessible sites.
 ...
PMID:Apoptosis in atypical fibroxanthoma and pleomorphic malignant fibrous histiocytoma. 918 7

The most common cancer arising from an old burn scar is squamous cell carcinoma, while malignant melanoma is rare. There are only four reports in the literature on the combination of the more common tumour with a malignant melanoma and only two cases of malignant fibrous histiocytoma alone. This paper reports the first occurrence of the combination of all three types of cancer in burn scars of the same patient. The factors that promote malignant transformation, such as immunological factors and karyotype, are discussed. We also performed an immunohistochemical study using anti-p53 antibodies.
 ...
PMID:Squamous cell carcinoma, malignant melanoma and malignant fibrous histiocytoma arising in burn scars. 941 44

Epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) receptors are implicated in the development and progression of several malignancies including osteogenic and soft tissue sarcomas (STS). To determine a role for ligand-mediated receptor activation in sarcoma progression, the relative expression and function of EGF-R, IGF-I-R, and several other molecular determinants implicated in the progression of mesenchymal neoplasms were evaluated in human sarcoma cells established from surgical specimens of primary and metastatic tumors. mRNA blot analyses demonstrated the expression of c-Met, p53, and MDM2-specific transcripts. Western blot analyses confirmed the production of high levels of p53 protein; however, minimal levels of MDM2 and c-Met proteins were detected. Analysis of STS cells #23, #26, and #50 originating from an unclassified sarcoma lung metastasis, a malignant fibrous histiocytoma lung metastasis, and a dedifferentiated chondrosarcoma, respectively demonstrated high steady-state levels of EGF-R and IGF-I-R mRNA transcripts and protein correlating with receptor-specific tyrosine kinase activity and autophosphorylation in response to ligand. Treatment of these STS cells with EGF resulted in a >5 fold increase in DNA synthesis and mitogenesis compared with untreated controls. In contrast, treatment with IGF-I showed a variable STS growth response correlating with the origin of the tumor. These data support the involvement of EGF-R and IGF-I-R in the growth and metastasis of human soft tissue sarcoma and may offer new targets for therapeutic intervention in the management of this disease.
 ...
PMID:Epidermal growth factor receptor and insulin-like growth factor-I receptor expression and function in human soft-tissue sarcoma cells. 945 58

Both tumor suppressor genes p53 and p16(INK4A) play a crucial role in the control of cell cycle and tumor development. In this study 19 malignant fibrous histiocytomas of the bone (MFH-b), a very rare sarcoma entity, were investigated for mutations in p53 and p16 genes by a PCR-SSCP-sequencing analysis. In the tumor samples two p53 mutations and two polymorphisms (one in the p53 gene and one in the p16 gene) were found. The occurrence rate for p53 mutations and the absence of p16 mutations in MFH-b are comparable to the findings for MFH of soft tissues (MFH-st) and osteosarcomas, suggesting that p53 rather than p16 may play a role in tumorigenesis of MFH-b.
 ...
PMID:How is the mutational status for tumor suppressors p53 and p16(INK4A) in MFH of the bone? 948 81

A follow-up investigation of 25 cases of extraskeletal osteosarcomas diagnosed at the Center for Bone and Soft Tissue Tumors, Aarhus University Hospital, Denmark, in the period from 1970-1995 was undertaken. The immunohistochemical profile of these tumors was evaluated using a panel of 10 antibodies, and the value of alkaline phosphatase staining in differential diagnostic situations also was considered. The study revealed that this tumor is high-grade malignant and affects adults (median age, 67 years; range, 35-82 years) at diagnosis. The thigh (52%) was the most common tumor location. Seven tumors were superficial, whereas the remaining 18 were intramuscular. Two patients with superficial tumors previously received radiation to the area. Local recurrences developed in 9 (36%) patients and distant metastases developed in the lungs in 15 (60%) patients as the most common site. Median survival time was 24 months, and the cause-specific survival rate at 5 years was less than 25%. Thirteen (52%) intramuscularly located extraskeletal osteosarcomas were of the fibroblastic subtype, often with sparse amounts of osteoid. They could be separated from malignant fibrous histiocytoma on the basis of a strongly positive alkaline phosphatase reaction. Immunohistochemistry did not reveal characteristic features because positivity for vimentin, occasional positivity for desmin, actin, S-100, epithelial membrane antigen, cytokeratin, and p-53 may be observed in many other pleomorphic sarcomas. Various histopathologic factors, such as tumor size, tumor depth, histopathologic subtype, malignancy grade (IIIA versus IIIB), MIB-1, and p53 reactivity were analyzed in relation to clinical course. Only MIB proliferation was correlated to prognosis, with significantly longer survival in patients with tumors with MIB-1 values less than 24%. Our study has shown extraskeletal osteosarcoma to behave in a highly aggressive fashion. Alkaline phosphatase staining compared with immunohistochemistry proved to be superior in the differentiation from other pleomorphic sarcomas.
 ...
PMID:Extraskeletal osteosarcomas: a clinicopathologic study of 25 cases. 959 29

We report the histological, immunohistochemical and ultrastructural findings of an exophytic cutaneous tumor composed of a mixture of typical basal cell carcinoma (BCC) and malignant fibrous histiocytoma. Nine previously reported carcinosarcomas of the skin are reviewed. We prefer the term "sarcomatoid carcinoma" for this rare neoplasm. Only the BCC showed a positive immunoreaction to cytokeratin; the sarcomatous component was negative, but it did express vimentin, and, focally, smooth-muscle-specific actin and KP1 (CD68). Both components showed p53 immunostaining.
 ...
PMID:Sarcomatoid carcinoma of the skin: report of a case. 964 Aug 85

The aim of the study was to evaluate the frequency of p53, mdm2 and Ki-67 immunopositivity in MFH, and to investigate possible associations of their expression with the grade of malignancy and predominant histological pattern--storiform, pleomorphic and myxoid subtype of MFH. A total number of 51 tumor samples from 21 primary and 30 secondary MFHs was studied using monoclonal anti-p53 (DO-78, DAKO), anti-mdm2 (1F2, NOVOCASTRA) and polyclonal anti-Ki-67 (DAKO) antibodies. The p53 immunopositivity was observed in 32.7% of all tumor samples (in 36.8% of primary and in 30% of recurrent and metastatic tumors). The mdm2 immunopositivity was noted in 34.8% of all tumor samples (in 33.3% of primary and 35.7% of secondary tumors). The mean percentage of p53, mdm2 and Ki-67 positive cells was 15.5, 8.8 and 7.05, respectively. The mean Ki-67 LI was statistically higher in grade 3 than in grade 2 of malignancy (p = 0.006). A significant correlation was found between mdm2 positivity and histological subtypes of MFH--storiform and pleomorphic types were more frequently mdm2 positive than myxoid variant (p = 0.035 and p = 0.009, respectively). No such correlation was observed for p53 positivity of tumors and subtypes, but there was a statistically significant difference in the percentage of p53 positive cells between storiform and myxoid type (p = 0.049). We also noted more tumors expressing high percentage (over 20%) of mdm2 positive cells in pleomorphic and storiform subtypes than in myxoid variant (p = 0.048). The Ki-67 LI was also higher in pleomorphic than in other types of MFH (p = 0.012). A strong positive correlation was found between p53 positivity and mdm2 positivity of tumors in primary MFHs (p = 0.00146). p53 and mdm2 positive tumors were mainly in grade 3 of malignancy, but no statistically significant correlations were noted. A positive correlation between the percentage of p53 positive cells and Ki-67 positive cells (p = 0.0028) was observed.
 ...
PMID:Immunohistochemical status of p53, mdm2 and Ki-67 in malignant fibrous histiocytoma. 964 Sep 70

Radiotherapy is known to cause secondary malignancies in the radiation field; postradiation sarcomas (PRS) are one example of such malignancies. Little is known about the genetic changes, including p53 gene alterations, that are thought to play a role in the tumorigenesis of human PRS. In the present study, p53 gene mutations were analyzed on paraffin-embedded specimens from 24 patients with PRS (4 men and 20 women) by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) followed by direct sequencing. The primary tumors of these patients were uterine cervical cancers in 14, breast cancers in 3, malignant lymphomas in 2, and others in 5. Total radiation doses ranged from 36 to 300 Gy (median, 60 Gy). The latent period between completion of radiation therapy and development of PRS ranged from 3 to 34 years (median, 10 years). Malignant fibrous histiocytoma was the most common PRS, accounting for 12 cases. PCR-SSCP revealed the aberrant mobility shifts of bands in 24 cases: 21 shifts in exon 5, 18 in exon 7, and 12 in exon 8. Direct sequencing of the SSCP product revealed a total of 58 mutations in 21 (88%) of 24 cases: 4 cases had a single mutation, 5 had 2 mutations, 5 had 3 mutations, 6 had 4 mutations, and 1 had 5 mutations. Although 31% of the mutations did not change an amino acid, every tumor had at least one mutation that did, which may have provided the selection pressure for expansion. The frequency of p53 gene mutation in sporadic soft tissue sarcomas was 20%. These findings highlighted the extraordinarily high frequency of p53 gene mutations in PRS. G:C to A:T transition at dipyrimidine sites was found in 14 (58%) of 24 cases. Collectively, these findings indicate that radiation is causative for soft tissue sarcomas via p53 gene mutations.
 ...
PMID:Mutation of the p53 gene in postradiation sarcoma. 964 63


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