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)

Samples from 94 ovarian tumors, comprising 24 cystadenomas/adenofibromas, among them 6 benign and 18 borderline tumors, one benign Brenner tumor, 39 carcinomas, 17 sex-cord stromal tumors, 5 germ-cell tumors and 8 metastatic or recurrent neoplasms were screened for p53 aberrations by polymerase chain reaction (PCR), temperature-gradient gel electrophoresis (TGGE), direct sequencing and immunohistochemistry. All sex-cord stromal and germ-cell tumors showed wild-type p53, except for a heterozygous silent germ-line mutation in one androblastoma. Somatic p53 mutations were detected in only one tumor of the cystadenoma/adenofibroma series (4.2%), in contrast to 38.5% of the carcinomas, among them 57.1% of serous papillary carcinomas, and 12.5 to 22.2% of endometrioid and mucinous carcinomas. By direct sequencing, the mutations of 13 cases were qualified as mis-sense mutations (n = 10), or 1 to 2-bp deletions (n = 3). Only 2 cases were immunohistochemically positive in the absence of detectable p53-gene abnormalities. The presence of p53 aberrations was significantly correlated with high grade, but not with stage of disease. For 21 bilateral tumors and/or tumors spread to the peritoneum, samples from both ovaries and/or ascites were analyzed. Among these, 16 cases were identical as to the p53 genotype, 5 cases showed discordant p53 states in ovary and/or in ascites DNA. We conclude that somatic p53 mutations are very frequent in serous papillary carcinomas, particularly in tumors of high grade, bilaterality, and peritoneal spread, less frequent in other carcinoma types and extremely rare in borderline and benign tumors of the ovary.
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PMID:p53 mutations in ovarian tumors, detected by temperature-gradient gel electrophoresis, direct sequencing and immunohistochemistry. 766 49

Inhibin-alpha-deficient mutant mice have been generated by a targeted deletion of the inhibin-alpha gene through homologous recombination in murine embryonic stem cells. Essentially all of the homozygous mutants develop gonadal sex cord-stromal tumors. To investigate their endocrine and proliferative characteristics, gonadal tumor cells were maintained in vitro. Cells from inhibin-alpha-deficient mice multiplied poorly; however, cells from mice deficient in both inhibin-alpha and p53 proliferated rapidly and showed higher saturation density and plating efficiency, thus allowing the establishment of clonal tumor cell lines. Although negligible estrogen and testosterone was produced by the clonal cells, high levels of progesterone were secreted. A clonal testis tumor cell line (inhibin-alpha/p53 deficient) showed no response to exogenous FSH, human CG (hCG), or inhibin A but exhibited a 6- to 8-fold increase in progesterone production in response to forskolin treatment. The stimulatory effect of forskolin was, however, partially blocked by activin treatment. Northern blot analysis revealed inhibin beta A and beta B mRNA expression in these cells. Furthermore, Western blot analyses indicated the secretion of the beta A-subunit protein. We further tested the role of activin on tumor cell growth. Treatment with follistatin, an activin-binding protein, inhibited tumor cell replication in a dose-dependent manner. In contrast, treatment with activin A stimulated tumor cell growth by itself and partially blocked follistatin action. Incorporation of thymidine into DNA of these cells was also stimulated by activin. In addition, treatment with antiactivin A serum inhibited tumor cell replication and blocked the stimulatory action of activin on cell growth. The activin action is likely mediated by specific receptors because cross-linking of [125]activin to the 50-55 kilodalton type I and 75-80 kilodalton type II receptors was found using sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis. Northern blot analysis also revealed follistatin mRNA expression in the tumor cells, suggesting these cells are related to granulosa cells. Our findings indicate that activin can act as an autocrine growth factor in stimulating the proliferation of gonadal tumor cell lines derived from inhibin-alpha and p53-deficient mice and inhibits progesterone production. These tumor cell lines are useful for studies on the regulation of gonadal cell proliferation and steroidogenesis as well as the signaling pathway mediating activin action.
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PMID:Characterization of gonadal sex cord-stromal tumor cell lines from inhibin-alpha and p53-deficient mice: the role of activin as an autocrine growth factor. 799 39

The p53 tumor suppressor gene has been extensively studied in various human tumors including epithelial ovarian cancers. However, little is known about the expression of this gene in ovarian granulosa cell tumors, the most common histologic type of sex cord-stromal tumors. We investigated whether overexpression of the p53 gene product occurs in this specific ovarian tumor. Nineteen patients with ovarian granulosa cell tumors were recruited in this study. Immunohistochemical staining for the p53 protein with monoclonal antibody PAb 1801 was performed in the paraffin-embedded tissue of each case to screen for p53 overexpression. Among the 19 ovarian granulosa cell tumors, there was only one well-differentiated tumor found to have nuclear immunoreactivity in a small fraction of tumor cells. Polymerase chain reaction--single-stranded conformation polymorphism was used to study the tumor showing focal p53 positivity, but no mobility shift was noted from exon 4 through exon 9 of the p53 gene. On the basis of this observation, we propose that alteration of the p53 tumor suppressor gene is not a common finding in ovarian granulosa cell tumors.
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PMID:Overexpression of p53 is not a feature of ovarian granulosa cell tumors. 862 17

The biologic behavior of gastrointestinal stromal tumors is difficult to predict, and they can be best studied in a site-specific fashion. The aims of this study are to analyze the clinicopathologic parameters and assess the prognostic value of p53 (DO-7) and Ki-67 (MIB-1) immunoreactivities in small intestinal stromal tumors (SIST). The histopathologic features of 31 SIST were assessed and categorized into two groups as follows. Group A (clinically aggressive) in which death due to tumor, metastasis, recurrence or relapsed melena were seen (n = 15) and group B (clinically benign; n = 16). For both groups, the period of follow-up was 30-144 months. p53 overexpression was observed in four tumors (31%) in group A, and in none in group B. For groups A and B, the mean Ki-67 index was 16.8 +/- 12.5 and 8.4 +/- 12.6, respectively. Statistical analysis revealed that the significant predictors of malignancy were high cellularity (odds ratio (OR) = 999; 95% confidence interval (CI) = 0-999); p53 overexpression (OR = 999; CI = 0-999); size of tumor > or = 5 cm (OR = 18.0; CI = 1.9-171.9); > or = 5 mitoses/50 high-power fields (HPF) (OR = 17.1; CI = 1.8-165.9); pleomorphism (OR = 17.1; CI = 1.8-165.9); and necrosis (OR = 11.9; CI = 2.2-65.1; P < 0.05). High Ki-67 index (> or = 8.4) had a marginal impact on risk (OR = 4.1; CI = 0.8-20.2; P = 0.08). In conclusion, high cellularity, p53 overexpression, size of tumor > or = 5 cm, > or = 5 mitoses/50 HPF, pleomorphism and necrosis are important parameters for the prediction of malignancy in SIST.
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PMID:Small intestinal stromal tumors: a clinicopathologic study of 31 tumors. 970 40

The p53 gene controls the cell cycle by transactivating p21WAF1/CIP1, a cyclin dependent kinase (cdk) inhibitor. By inhibiting cdks, p21WAF1/CIP1 regulates the cell cycle by blocking the G1 to S phase transition. In this study, we analyzed the immunohistochemical expression of p21WAF1/CIP1 in 66 soft tissue sarcomas and its relationship to p53 and the cell cycle proliferation antigen Ki-67. Expression of p21WAF1/CIP1, was detected in 76% of the tumors and p53 in 26%. All malignant schwannomas, synovial sarcomas, leiomyosarcomas and gastrointestinal stromal tumors expressed p21WAF1/CIP1. The majority of angiosarcomas, dermatofibrosarcomas, and fibrosarcomas showed low expression or were negative for p21WAF1/CIP1. Ewing's sarcomas, liposarcomas, and malignant fibrous histiocytomas were heterogeneous in their expression of p21WAF1/CIP1. Combining p53 and p21WAF1/CIP1 staining, the following four patterns were observed: 23% of the tumors showed the p53+/p21+ pattern; 53% showed the p53-/p21+ pattern; 3% showed the p53+/p21- pattern and 21% were negative for both p53 and p21WAF1/CIP1. There was no correlation between Ki-67 and p21WAF1/CIP1 or p53 staining. Our results show that soft tissue sarcomas, independent of their histologic subtype, frequently express p21WAF1/CIP1 which is probably important in their tumorigenesis. Additionally, p21WAF1/CIP1 may play a role in determining the efficacy of various cell cycle-directed therapies in soft tissue sarcomas.
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PMID:Expression of p21WAF1/CIP1 in soft tissue sarcomas: a comparative immunohistochemical study with p53 and Ki-67. 982 Aug 64

The stomach is the most common gastrointestinal site of mesenchymal tumors which traditionally have been designated as smooth muscle tumors. However, with increasing analytic tools most investigators were unable to demonstrate true myogenic differentiation. Furthermore, the biological behavior of gastrointestinal stromal tumors (GIST) is difficult to predict. The aim of this study was to evaluate MIB-1 and p53 as additional prognostic markers, as well as myogenic differentiation immunohistochemically in GIST. 43 gastric stromal tumors were reviewed, 19 were classified as benign, and 10 as malignant. 14 tumors were considered indeterminate for biological behavior. In addition to MIB-1 and p53, immunohistochemistry was also performed for sm-actin, desmin and S 100-protein (ABC). 41 patients had a clinical follow-up of more than 2.5 years, 5 patients had metastases. Mean proliferation rates defined as percentage of MIB-1 positive tumor cells in 3 HPF were as follows: typical leiomyoma: 0.2%; benign GIST, spindle cell type: 1.8%; benign GIST, epithelioid cell type: 2.4%; borderline GIST, spindle cell type: 2.1%; borderline GIST, epithelioid cell type: 2.5%; malignant GIST, spindle cell type: 4.9%; and malignant GIST, epithelioid cell type: 7.3%. All 5 metastasizing tumors had a proliferation index > 4% (p < 0.0001). 4/5 metastasizing tumors had p53 positive cells (p < 0.05). 36/43 tumors were sm-actin positive, 7 of which were positive for desmin as well. Classification of gastric mesenchymal tumors as GIST is appropriate because only a small percentage show true smooth muscle differentiation. A MIB-1 proliferation index above 4% might indicate a more aggressive course, as well as p53 positivity.
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PMID:[Prognostic factors of gastrointestinal stromal tumors of the stomach]. 1009 44

Gastrointestinal mesenchymal tumors traditionally have been designated as smooth muscle tumors. However, with increasingly accurate analytic tools most investigators were unable to demonstrate true myogenic differentiation. Diagnostic criteria and grading vary among different studies and the biological behavior of these gastrointestinal stromal tumors (GIST) is difficult to predict. In this manuscript the recent concept of GIST is reviewed, including a suggestion for tumor classification. Furthermore, MIB-1 and p53 immunohistochemistry and myogenic differentiation were evaluated as potential prognostic factors. Diagnosis requires the use of immunohistochemistry. Classification as GIST seems appropriate, since only few tumors show complete myogenic differentiation. Besides a tumor size over 5 cm, mitotic rate still seems to be the best predictor of treatment failure in tumors that are resected with a rim of uninvolved tissue. MIB-1 proliferation index above 4% and p53 positivity indicate a more aggressive course.
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PMID:[Current classification of gastrointestinal stromal tumors]. 1113 18

Ancillary techniques such as immunohistochemistry (IHC) enable the surgical pathologist to extract additional information from fixed, deparaffinized tissue specimens and to provide data critical to optimal clinical management of the patient. In this review of applications of IHC to the analysis of gynecologic malignancies, the usefulness of immunohistochemical analysis of neoplasms of the cervix, endometrium, and ovary is summarized. In the uterine cervix, dysplasia is associated with qualitative and quantitative alterations in the expression of the Ki-67 antigen expression, as well as an ability to detect human papillomavirus. Endometrial endometrioid adenocarcinomas display a highly characteristic immunophenotype, with coexpression of cytokeratin and vimentin and demonstration of foci of high molecular weight cytokeratin expression; in addition, IHC analysis of estrogen and progesterone receptor and p53 expression can provide important prognostic information about this tumor. Stromal tumors of the endometrium may display a partial smooth muscle immunophenotype, but novel markers such as CD10 provide new tools for the identification of these tumors. The immunophenotypes of the normal ovarian surface epithelium (OSE) and corresponding tumors display significant overlap with, but important distinctions from, mesothelium, and important new markers such as the Wilms tumor gene product can prove useful in the identification of carcinomas of the OSE. Important prognostic markers for carcinomas of the OSE include the HER-2/neu gene product and p53, alterations of which can both be assessed by IHC techniques. Finally, the recent availability of markers of ovarian stroma, including Melan-A and inhibin-alpha, has provided a means for the positive identification of ovarian stromal tumors, which can manifest protean histological appearances.
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PMID:Immunohistochemical analysis of gynecologic tumors. 1119 73

The understanding of gastrointestinal stromal tumors (GIST) is complex because of their divergent differentiation and unpredictable behavior. However, our understanding is becoming clearer, despite some cases of tumors which are exceptions from the typical cases. Tumor size, mitotic rate and, to a lesser degree, location, are the most important predictive parameters for the behavior of GIST. In this study, expression of p53 protein was evaluated in 15 cases of GIST. Tumors were divided into three groups: (i) benign (mitotic index [MI] < 5/50 high-power fields [HPF] and size < 5 cm); (ii) borderline (MI < 5/50 HPF and size > or = 5 cm); and (iii) malignant (MI > or = 5/50 HPF, irrespective of size). The mean values of p53 expression in the three groups were significantly different (benign, 10.6%; borderline, 33.8%; and malignant, 71%). The conclusion of the present study is that p53 overexpression correlates well with the malignant potential of GIST.
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PMID:p53 expression in gastrointestinal stromal tumors. 1147 64

Gastrointestinal stromal tumors (GIST) are a heterogeneous group of neoplasms whose biologic behavior is difficult to predict. The aim of this study is to evaluate the prognostic value in GIST of some oncoproteins involved in regulation of cell proliferation. Tumor size, mitosis, necrosis, and p53, c-myc, and bcl-2 protein expression of 32 GIST were studied. Proliferative index was assessed with Ki67. The 32 cases were grouped into the following clinical categories: (1) clinically benign (BN) were defined as disease-free survival greater than 3 years (n=10); (2) clinically malignant (MN) in which local recurrence or metastasis occurred regardless of the follow-up time (n=15); and (3) clinically indeterminate (ID) owing to follow-up <3 years without metastasis or local recurrence (n=seven). Discriminant analysis was used to allocate any tumor to one of the two prognostic groups (BN or MN). In univariate analysis all six factors studied above proved to be of significant prognostic value. Using a multivariate stepwise discriminant analysis to take into account the interrelationship between factors, we found that c-myc expression was the most important prognostic factor, followed, in order of statistical weight, by size and Ki67. These were combined to define a discriminant score ([10.75 x c-myc]+[0.39 x size]+[0.078 x Ki67]-15.54=score), which was capable of correctly identifying tumors in our series whose known clinical behavior was BN or MN in 92% of the cases. The classification score was applied subsequently to the seven clinically ID cases: Three (42.9%) were predicted as BN, and four (57.1%) were predicted as MN. Both expression of oncoprotein c-myc and the proliferative index provide prognostic information in GIST, in addition to morphologically established prognostic factors such as size. These factors in a discriminant analysis proved to be useful for the clinical classification of GIST into BN or MN and to predict the clinical outcome of clinically ID tumors. Int J Surg Pathol 8(2):133-144, 2000
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PMID:Predicting Metastatic Risk of Gastrointestinal Stromal Tumors: Role of Cell Proliferation and Cell Cycle Regulatory Proteins. 1149 78


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