Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An epithelial ovarian cancer cell line is established from a patient with recurrent familial ovarian cancer. Two of the patient's sisters and her mother have also had ovarian cancer. The histological resemblance of the cell line to the patient's Stage IV, Grade 3 papillary serous ovarian primary cancer is striking. The cell line does not secrete CA125 and is estrogen and progesterone receptor negative. Overexpression of the p53 tumor suppressor gene but not the HER-2/neu oncogene was detected by immunohistochemical analysis. An unusual chemosensitivity to cisplatin, doxorubicin, etoposide, and taxol is demonstrated, suggesting that a chemosensitivity mechanism might explain prolonged survival of some patients with familial ovarian cancers. This truly unique cell line should prove invaluable in the further evaluation of molecular genetic changes associated with familial ovarian cancers.
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PMID:Isolation and preliminary characterization of an ovarian carcinoma cell line from a patient with familial ovarian cancer. 782 46

The aim of this investigation was to study the prevalence of p53 gene mutations and allelic deletions in ovarian cancer and the relationship between these events and p53 expression. Genomic p53 was amplified by the polymerase chain reaction (PCR) from paraffin-embedded sections of tumour and non-tumour tissue. Exons 5-9 were screened for mutation using non-isotopic single-strand conformation polymorphism (SSCP) analysis. Allelic deletions at a sequence polymorphism in exon 4 were studied for loss of heterozygosity (LOH) by restriction analysis and by SSCP. p53 expression was detected by immunohistochemistry with the p53 antibodies CM1 and Do7. Of 44 cases, ten (23 per cent), including a mucinous tumour of low malignant potential, showed mutations. There was a statistically significant correlation between p53 mutation and expression (P < 0.01) but seven cases showed discordance. Of 18 informative cases, eight (44 per cent) demonstrated LOH. Mutations were identified in three of the informative cases, two of which also had LOH. The remaining case showed mutations in two amplicons. p53 dysfunction, as indicated by mutation, deletion, or increased expression, is common in ovarian cancer. There is an association between these molecular events but the exact mechanisms of p53 inactivation remain to be elucidated.
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PMID:p53 expression, mutation, and allelic deletion in ovarian cancer. 782 48

This review discusses recent insights into the roles of the p53 tumor-suppressor gene and growth factors in the development of ovarian cancer and describes the genes implicated in familial ovarian cancer syndromes related to the MSH2 (Lynch II) and BRCA1 (breast and ovarian cancer) genes. Evidence of the monoclonality of ovarian cancer, which contrasts with data supporting the polyclonal origin of primary peritoneal carcinoma, is presented. Finally, the roles of the human papillomavirus and the HIV virus in the etiology of cervical cancer are analyzed in view of the growing importance of this HIV-associated cancer and the poor outcome in these patients.
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PMID:Advances in the biology of gynecologic cancer. 782 56

The effect of human wild type and mutant p53 proteins on the human multidrug resistance (MDR1) promoter was studied in a p53-negative human cell line. Transient expression of MDR1 promoter-chloramphenicol acetyltransferase reporter gene constructs (MDRCAT) cotransfected with p53 expression vectors was analyzed in H358 lung carcinoma cells. Cotransfection with a wild type p53 expression vector stimulated MDRCAT activity, while cotransfection with mutant p53 expression vectors altered at amino acid positions 181, 252, 258, or 273 failed to stimulate expression. Wild type p53 stimulation of MDRCAT activity was time dependent with maximal expression occurring 24-30 h following transfection and correlating with high p53 protein levels. MDR1 promoter deletion analysis suggested that the sequences involved in wild type p53 stimulation of MDRCAT activity were contained within the region from -39 to +53 relative to the start of transcription at +1. This region contains no TATA or p53 consensus binding sequence but does contain an initiator sequence. Wild type p53 stimulation of MDRCAT expression also occurred in parental and doxorubicin-resistant SW620 colon and parental 2780 ovarian cancer cell lines, indicating that wild type p53-mediated simulation of the MDR1 promoter is not restricted to a single cell line.
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PMID:Wild type p53 stimulates expression from the human multidrug resistance promoter in a p53-negative cell line. 782 27

Familial cancer clusters provide a unique opportunity to elucidate the molecular mechanisms central to the development of malignancy. We have identified four families in which 11 members developed epithelial ovarian cancer. The clinical course of disease in these individuals with familial ovarian cancer appears to be very different from that of patients with nonfamilial ovarian cancer. In order to compare these disease states, 34 cases matched for age at diagnosis (57 years), tumor histology (all adenocarcinomas), and a preponderance of advanced grade and FIGO stage of disease were selected. Patients with familial ovarian cancer exhibited a 67% 5-year survival in comparison with a 17% 5-year survival in the nonfamilial ovarian cancer cases. Preliminary studies indicate a lack of overexpression of the HER-2/neu oncogene in the familial cancer members' tumors. This may correlate with the indolent character of their disease. Abnormal p53 tumor suppressor gene expression was noted in four of six cancers tested. We also found germ line p53 mutations in three of the four families, but neither the germ line or tumor p53 prevalence was 100%. This is the first report of germ line p53 mutations associated with familial ovarian cancer and indicates that this gene may play a role in the development of some familial ovarian cancers.
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PMID:Familial ovarian cancer. 790 48

Seventy-nine ovarian serous and mucinous borderline tumors, 36 stage I carcinomas and 39 stage II-IV carcinomas were studied for p53 protein accumulation with monoclonal antibody PAb1801.p53 protein was expressed in 14% of borderline tumors, 36% of stage I carcinomas, and 64% of higher stage carcinomas. All immunopositive carcinomas accumulated p53 protein in the primary tumor, and 95% of them showed concordance in staining among different tissue blocks. A difference in frequency of p53 protein accumulation between stage I and higher stage serous carcinomas was not statistically significant. p53 positivity was associated with microinvasion, microcarcinoma and coexistent carcinoma in mucinous borderline tumors (P = .025). An association between p53 protein expression and poor tumor differentiation in Stage I carcinomas as statistically significant (P = .03). p53 positivity was observed in a poorly differentiated endometrioid carcinoma as well as in adjacent benign endometriotic tissue. These results suggest that p53 abnormalities may be early events in ovarian cancer, possibly contributing to malignant transformation of some borderline tumors, endometriosis and other carcinoma precursors.
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PMID:p53 expression in ovarian borderline tumors and stage I carcinomas. 794 35

Immunohistochemical characteristics of undifferentiated carcinomas of the ovary were examined using formalin-fixed, paraffin-embedded tissues with an avidin-biotin staining approach. Eight cases were collected from the pathology files of our Institute from a total of 214 recorded malignant ovarian tumors. For immunostaining, antibodies reacting with epithelial membrane antigen (EMA), pankeratin, vimentin, CA 125, CA 19-9, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), alpha-1-antitrypsin (AT), epidermal growth factor receptor (EGFR), c-erbB-2, bcl-2 and p53 proteins were used. All the cases examined were positive for EMA and pankeratin, specific markers for epithelial tumors, negative for the non-epithelial tumor marker, vimentin, and also positive for EGFR. Interestingly, only one case was positive for CA 125, despite it being one of the commonest reported indicators of ovarian cancer. CA 19-9 was positive in 7 cases, CEA in 5, AFP in 2, AT in 6 and c-erbB-2 protein in 4. Two cases were positive for p53 protein, and in 1 of these positive staining for bcl-2 was also observed. These results indicate that the epithelial nature is well preserved in undifferentiated ovarian carcinomas, although consistently positive reactions were not observed within the cases for some antigens. They further clearly show that a negative signal for CA 125 can not be considered to exclude the possibility of a primary ovarian tumor.
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PMID:Immunohistochemical characterization of undifferentiated carcinomas of the ovary. 796 44

Mutations at the p53 tumor suppressor gene locus are a frequent genetic alteration associated with human ovarian carcinoma. Little information exists regarding whether mutational events occur other than point mutations and large deletions, causing loss of heterozygosity. Small intragenic deletions and insertions in the p53 gene have been observed in various human neoplasias. We developed a multiplex polymerase chain reaction (MPCR) screening assay to amplify the complete p53 coding region from genomic DNA in a single step. Deletions and/or insertions were found in six out of 11 newly established ovarian carcinoma cell lines. MPCR detected deletions as small as 2 bp, as confirmed by nucleotide sequence analysis. Most of the observed alterations (6/7) were homozygous or hemizygous. Structural aberrations of the p53 gene possibly leading to loss of p53 cell cycle control may be a consequence of a slipped-mispairing mechanism in rapid DNA replication during repetitious ovulation and wound repair of ovarian epithelial cells. MPCR may be a valuable tool for screening for possible p53 deletion and insertion mutations not only in ovarian cancer but also in other malignancies.
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PMID:Multiplex PCR screening detects small p53 deletions and insertions in human ovarian cancer cell lines. 800 84

Four genes are now known to be responsible for inherited susceptibility to breast cancer: the BRCA1 gene on chromosome 17q21, the ataxia-telangiectasia (AT) gene (11q22-q23), the TP53 gene (17p13.1) and the androgen receptor (AR) (Xq11.2-q12). These genes, however, differ dramatically in terms of the risk of breast cancer that they confer, the proportion of breast cancer incidence that they account for and the other cancers and other phenotypes with which they are associated. Genetic linkage studies have shown that some high risk breast cancer families, particularly those where breast cancer occurs in association with ovarian cancer, are due to a gene on chromosome 17q known as BRCA1. The BRCA1 gene is estimated to confer a breast cancer risk of about 70% by age 70, and may account for about 2% of overall breast cancer incidence, although a higher proportion of younger cases. Germline mutations in the TP53 gene are responsible for a high proportion of LI-Fraumeni families, in which breast cancer occurs in association with childhood sarcomas and other cancers. In such families, the risk of breast cancer is over 50% by age 50, and the risk of all cancers is nearly 100%; germline TP53 mutations are, however, probably responsible for much less than 1% of all breast cancer. By contrast, heterozygotes for the AT gene carry a much more moderate risk of breast cancer. This gene, however, is much more common in the population and may account for 7% or more of breast cancer incidence. Finally, germline mutations in the androgen receptor are known to cause male breast cancer, but this has only been demonstrated in two families. Evidence from linkage and population based studies suggests that these genes may account for about one half of the observed familial clustering of breast cancer; other breast cancer susceptibility genes therefore remain to be identified.
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PMID:Inherited susceptibility to breast cancer. 801 3

We explored the value of p53 immunostaining in detection of malignant cells in cytologic analyses in ovarian cancer patients. Ninety-six percent of 23 tumor touch preparations had nuclear staining with PAb240: 44% had nuclear only, 26% had both nuclear and cytoplasmic staining, and 26% had cytoplasmic staining alone. Eight of 20 cytospins of peritoneal washings from ovarian cancer patients were PAb240 positive, 6 had cytoplasmic, and two had nuclear staining. Cytospins of fluid from 3/15 patients with no malignancy revealed cytoplasmic staining of mesothelial cells. The lack of concordance between staining of primary tumors and cytospins of peritoneal washings and the apparent reactivity in some benign samples may limit the utility of immunohistochemical detection of malignant cells in the peritoneal fluid of ovarian cancer patients.
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PMID:Detection of p53 antigen expression in cytologic preparations of ovarian carcinomas. 806 2


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