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)

The family of Ewing tumors (ET) is characterised by a unique gene rearrangement which is represented by a translocation t(11;22) (q24;q12) or a deletion del 22q12 in most cytogenetically analysable cases. The recent cloning of the underlying gene fusion provides the basis for the diagnostic detection of minimal amounts of residual tumor cells at resection margins, in blood and bone marrow. In addition, the very first steps in ET tumorigenesis can be studied on a functional basis. In this study, a variety of fusion products were identified with a sensitivity of 10(-6) by means of RT-PCR. In 20 of 22 ET, a gene rearrangement was identified which resulted in the substitution of the effector domain of one of the closely related DNA-binding oncogenes, FLI-1 or ERG, by the transactivating domain of a new gene, EWS. Presumably, the oncogene and consequently its target genes are activated by this type of translocation. If the EWS domain was replaced with a transcriptionally irrelevant domain by transfection of a recombinant gene into ET cells, competition with the endogenous chimeric oncogene-product for DNA-binding was observed resulting in a partial growth inhibition. Activation of FLI-1 has been previously shown to occur as a primary event in Friend virus induced mouse erythroleukemia. During progression of this disease, inactivating p53 mutations have been observed frequently. In contrast, such aberrations were found to be extremely rare in ET.
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PMID:[The EWS gene rearrangement in Ewing tumors: key to the disease]. 796 16

Epithelial ovarian tumors of varying malignancy as well as normal ovaries were examined for their expression of p53 with the monoclonal antibody PAb1801. Immunohistochemical detection of p53 protein is possible when the gene has been mutated, but not when the normal gene product alone is present. Our results indicate that this tumor suppressor gene may be involved in tumorigenesis, as its expression was detected in both borderline and malignant tumors while normal ovaries and benign ovarian tumors were unstained with the p53 antibody. The presence of p53 was also related to dissemination of disease, residual tumor bulk, and poor differentiation as well as the presence of the proliferation variable Ki-67, another negative prognostic variable. No significant relation could be detected to S-phase fraction or DNA ploidy. Furthermore, the presence of p53 in malignant epithelial ovarian tumors was related to significantly decreased patient survival, with only 36% alive compared to 70% in the p53-negative group (P = 0.002). In the subgroup of patients with residual tumor burden after surgery, those with p53-positive tumors had a significantly (P = 0.05) decreased survival compared to those with p53-negative neoplasms, which further supports an independent role in ovarian cancer malignancy.
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PMID:p53 expression in epithelial ovarian neoplasms: relationship to clinical and pathological parameters, Ki-67 expression and flow cytometry. 820 2

Because little is known about the importance of apoptosis and its regulation in epithelial ovarian cancer, the authors looked for bcl-2 expression and p53 accumulation by immunohistochemistry in 148 ovarian carcinomas of different histologic types and stages. The number of apoptotic cells was assessed in situ by enzymatic detection of DNA fragmentation. Strong bcl-2 expression correlated with low histologic grade (P = .004) and was most often seen in endometrioid carcinomas (P = .001), whereas p53 accumulation was predominantly found in serous and undifferentiated carcinomas (P <.001) and high grade tumors (P <.001). p53 accumulation was associated with advanced tumor stage (P <.001) and the presence of residual disease after surgery (P <.001). Apoptosis increased with histologic grade (P = .012); apoptotic cells were sparse or absent in tumors of low malignant potential and mucinous carcinomas, but found in all other carcinoma types (P = .001). Apoptosis, bcl-2 expression, and p53 protein accumulation were not correlated with each other. The analysis of the postoperative course of 110 patients showed that survival depended on histologic tumor type (P = .0037), histologic grade (P = .0143), FIGO (International Federal of Gynecology and Obstetrics) stage (P = .0001), and absence or presence of postoperative residual tumor mass (P = .0001). p53 accumulation was also associated with adverse prognosis (P = .0001). However, bcl-2 positive carcinomas who had a statistically significantly better outcome than patients with p53 positive and bcl-2 negative tumors (P = .0443). Regarding FIGO stage and p53 alone in a Cox model, p53 proved to contribute additional prognostic information both in FIGO stages I/II as well as in FIGO stages III/IV. Thus, our observations point to different molecular alterations possibly underlying phenotypic diversity of ovarian carcinomas and provide clues for a better understanding of tumor progression in these neoplasms. Apoptosis plays a role in ovarian carcinomas, but seemingly is regulated in a different way than in nonneoplastic tissues.
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PMID:bcl-2 expression, p53 accumulation, and apoptosis in ovarian carcinomas. 860 16

The aim of the present study was to determine the activity of a combined regimen of mitoxantrone (DHAD) and ifosfamide (IFO) and identify clinical and biological factors with prognostic importance for the second-line treatment of ovarian cancer. The following factors were investigated for their prognostic importance: age, disease sites, platinum responsiveness, histological grade, the presence of clinically/radiologically detectable versus not detectable disease, residual disease volume after first surgery, p53 protein, c-erbB-2 oncoprotein and laminin receptor. 72 patients entered the trial. DHAD and IFO therapy led to a 15% response rate among the 47 cases with clinically/radiologically detectable disease (1 complete and 6 partial responses), with a median response duration of 4 months. The response rate was significantly different according to platinum responsiveness (4% objective responses in platinum-resistant versus 27% in platinum-sensitive disease). The time to treatment failure (TTF) and overall survival (OS) were affected by the presence of clinically detectable disease at study entry (median TTF 4 months in the presence of clinically/radiologically detectable disease versus 9 months if the disease was not similarly detectable, P = 0.02; median OS 10 months versus 21 months, P = 0.01). Initially overexpressed in only a few tumours, the c-erbB-2 oncoprotein became overexpressed in 36% of platinum-resistant tumours; this modulation did not occur in platinum-sensitive tumours. Furthermore, laminin receptor was expressed in 77% of platinum-sensitive versus 39% of platinum-resistant patients. There were no differences in p53 protein expression according to drug responsiveness.
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PMID:An I.T.M.O. group study on second-line treatment in advanced epithelial ovarian cancer: an attempt to identify clinical and biological factors determining prognosis. 865 51

Chronic myeloid leukaemia (CML) is characterized cytogenetically by a t(9;22)(q34;ql1) reciprocal translocation which gives origin to a hybrid BCR-ABL gene, encoding a p2lO(BCR-ABL) fusion protein with elevated tyrosine kinase activity and transforming abilities. The t(9;22) was suggested to be associated with genomic imprinting of centromeric regions of chromosomes 9 and 22, but the genes directly affected by the translocation, ABL and BCR, were shown not to be imprinted. For most diagnostic and research purposes the BCR-ABL gene can be efficiently identified by reverse-transcription and polymerase chain reaction (RT/PCR) amplification of its fusion transcripts, which can be quantified by competitive PCR and similar assays for assessment of residual disease in the follow-up of therapy. In the great majority of CML patients the BCR-ABL transcripts exhibit a b2a2 and/or a b3a2 junction; in rare cases, the only detectable BCR-ABL transcripts have unusual junctions, such as b2a3, b3a3, e1a2 or e6a2. There is a recent suggestion that the BCR-ABL gene may not be always 'functional', since extremely low levels of BCR-ABL transcripts can be found in leucocytes from normal individuals and, conversely, it appears that no BCR-ABL transcription can be detected in a proportion of Ph-positive haematopoietic progenitors from some CML patients. The role, if any, of the reciprocal ABL-BCR hybrid gene in CML is unknown. Although its mRNA message is in frame, no ABL-BCR fusion protein has yet been identified in CML patients. The blast crisis of CML has been variably associated with abnormalities of proto-oncogenes, such as RAS and MYC, or of tumour suppressor genes, in particular RB, p53 and p16, or with the generation of chimeric transcription factors, as in the AML1-EVI1 gene fusion. It is likely, therefore, that multiple and alternative molecular defects, as opposed to a single universal mechanism, underlie the acute transformation of the disease.
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PMID:The molecular biology of chronic myeloid leukaemia. 865 67

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.
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PMID:Malignant meningioma: a clinicopathologic study of 23 patients including MIB1 and p53 immunohistochemistry. 865 46

Pure protoplasmic astrocytomas are a group of rarely encountered low grade astrocytic neoplasms. Relatively few studies have specifically examined this subset of tumors. A series of 18 protoplasmic astrocytomas in 14 males and four females (age range 2.5-52, mean 22 years) were studied in order to examine MIB1 (a marker of cell proliferation) and p53 (a tumor suppressor gene) immunoreactivity. All patients presented with seizures (mean duration 94 months) and three with headaches also. Eight tumors were located in the temporal lobe and six in the frontal lobe. All tumors were characterized by a proliferation of astrocytes with round nuclear contours arranged against a microcystic background. Only rare foci of mild vascular proliferation (3 tumors), rare mitotic figures (1 tumor), and mild nuclear atypia (3 tumors) were observed. Most tumors were primarily cortical in location. Necrosis was not seen in any of the tumors. MIB1 indices (number of MIB1 positive tumor cells/1000 tumor cells evaluated x 100) ranged from 0 to 4.3 (mean 0.7); in five tumors, no MIB1 staining was observed. p53 immunoreactivity was noted in 5 of 18 tumors (28%). Five patients received adjuvant radiation therapy and one adjuvant chemotherapy. At last known follow-up, 11 patients are alive with no evidence of residual tumor (mean 70 months), six patients are alive with evidence of residual tumor (mean 58 months), and one patient died of complications unrelated to the tumor (36 months) postoperatively. Based on these findings, the conclusions presented are as follows: (i) MIB1 indices are generally low in these tumors, corroborating the clinical impression of a slow growing neoplasm; and (ii) p53 immunoreactivity is observed in a minority of protoplasmic astrocytomas.
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PMID:MIB1 and p53 immunoreactivity in protoplasmic astrocytomas. 897 Jan 95

The pathogenesis of primary carcinoma of the fallopian tube (PCFT) is poorly understood. Tumor suppressor p53 gene alterations are common in human malignancies, but their role in the tumorigenesis and survival of PCFT is undefined. The objectives of this study were to define the occurrence and prognostic role of p53 alteration in PCFT and to examine the efficiency of immunohistochemistry (IHC) in detecting p53 alteration in PCFT. Fifty-two PCFT and 10 normal fallopian tubes were examined for p53 alteration by IHC and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP). The Kaplan-Meier method was used to derive the survival function, while the log-rank test was used to compare curves for two or more groups. Other patients' characteristics were analyzed by two-tailed Fisher's exact tests. IHC correlated well with PCR-SSCP with 100% sensitivity and 83.3% specificity for detecting p53 alteration in this study. Thirty-one of 52 (57%) PCFT showed p53 alteration. Alteration of p53 occurred in all stages of PCFT with a similar incidence in carcinoma in situ and late-stage disease. Alteration of p53 was related to tumor histologic type. Significant survival difference was noted between advanced and early clinical stages but no such difference was identified among different tumor grades. Compared to the p53-nonaltered group, the presence of p53 alteration in PCFT was related to significantly decreased patient survival (RR = 6.8, 95% CI = 2.9-16.2) in multivariate analysis. In the subgroup of patients with residual tumor after surgery, those with p53-altered tumors had a significantly decreased survival compared to those with p53-nonaltered group (RR = 7.4, 95% CI = 1.9-28.2). Alteration of p53 is common and IHC is an efficient method to detect p53 alteration in PCFT. Shorter survival is associated with p53 alteration which is an independent marker for the disease in this study. Alteration of p53 may be an early event in tubal tumorigenesis and may play an important role in the development of PCFT. Whether detection of p53 alteration may serve as an indicator of high-risk patients for whom more aggressive adjuvant chemotherapy may be considered needs to be explored in the future.
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PMID:Early occurrence and prognostic significance of p53 alteration in primary carcinoma of the fallopian tube. 899 45

Adducts, formed by carcinogens of tobacco smoke with DNA, can be detected by means of molecular techniques and are used as marker of internal exposure. Carcinogen-DNA adducts produce specific mutations in tumor-suppressor genes (e.g. p53) and oncogenes (e.g. ras), which can be involved in tumor initiation or in later stages of tumor progression (e.g. evolution of an invasive phenotype). Benzo(a)-pyrene, an important carcinogen of tobacco smoke, induces GT transversions, as demonstrated in in vitro systems and animal models. Mutations in the p53- or ras-gene are more common in human tumors of the lung, head and neck, bladder and pancreas in smokers than in non-smokers. Molecular biology of cancer gains increasing significance in clinical practice since 1.) the presence of certain mutations confers an unfavorable prognosis to malignant disease (e.g. ras mutations in lung cancer), 2.) ras and p53 mutations often occur early during tumor development and can thus facilitate diagnosis of malignant disease, and 3.) minimal residual disease can be detected using molecular techniques. After resection of cancer of the head and neck, tumor recurred more frequently in patients with no evidence of residual disease as assessed by pathohistologic criteria than in patients with no evidence of residual disease as evaluated by p53 immunostaining.
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PMID:[Molecular biology of tobacco smoke associated neoplasia]. 901 41

Abnormalities in p53 gene expression have been implicated in many inherited and sporadic forms of malignancies in humans. Immunohistochemical staining using monoclonal antibody D0-7 for the p53 protein expression was performed in 81 cases of pure DCIS, 14 benign breast lesions and 2 cases with normal breast tissue. Expression of p53 protein was detected in 15 (18.5%) cases of pure DCIS. Thirteen (25%) of the 52 comedo type DCIS showed p53 protein expression compared with 2 (6.9%) of the 29 non-comedo types (P < 0.02). p53 protein expression was also associated with high nuclear grade (P < 0.001) and high mitotic index (P < 0.05). The pattern of p53 protein staining was diffuse in one comedo type DCIS, regional in 6 comedo types, and focal in the remaining 8 cases (6 comedo type and 2 micropapillary type DCIS). The patient with comedo type DCIS showing diffuse staining has a family history of breast cancer in the first and second degree relatives (sister and maternal aunt). Clinical follow-up data was available in 52 cases. Follow-up period ranged from 9 to 55 months. Three patients, who were primarily treated by local excision, have had a documented local recurrence in the form of residual tumor within a short interval of 5 to 11 months. In all these three patients both the original and the recurrent tumors are negative for p53 protein expression. The difference in the local recurrence rate between p53 positive (0/15) and p53 negative (3/37) cased does not reach statistical significance (p > 0.05). We interpret that the local tumor recurrence in these three cases within a short period after primary excision is due to the presence of residual tumor at the excision site and is independent of the p53 gene alteration. It is concluded that p53 protein expression in DCIS is associated with comedo subtype, high nuclear grade, and high mitotic index, and is a promising new parameter to evaluate the cellular biology and prognosis of DCIS.
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PMID:p53 protein expression in ductal carcinoma in situ (DCIS) of the breast. 906 12


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