National Cancer Institute®
Last Modified: July 1, 2002
UI - 10094000
AU - Eisinger F; Geller G; Burke W; Holtzman NA
TI - Cultural basis for differences between US and French clinical recommendations for women at increased risk of breast and ovarian cancer.
SO - Lancet 1999 Mar 13;353(9156):919-20
AD - Department of Cancer Control and INSERM CRI 9703, Paoli-Calmettes Institute, Marseille, France.
UI - 11798075
AU - Su B; Guan M; Zhao R; Lu Y
TI - Expression of prostaglandin D synthase in ovarian cancer.
SO - Clin Chem Lab Med 2001 Dec;39(12):1198-203
AD - Department of Laboratory Medicine, Hua Shan Hospital, Fudan University, Shanghai, PR China.
Lipocalin-type prostaglandin D synthase (L-PGDS) has recently been shown to be expressed in human brain tumors and breast tumors. However, L-PGDS expression has not been investigated in ovarian cancer. The objective of this study was to determine whether L-PGDS is expressed in human ovarian cancer. Lipocalin prostaglandin D synthase mRNA was cloned and sequenced by RT-PCR. Using in situ hybridization (ISH) technique, the expression of L-PGDS mRNA in 54 ovarian cancer was investigated. Expression of L-PGDS mRNA was found in tumor cells of all various types of ovarian cancers. Patterns of staining of tumor cells varied among different histological types of ovarian cancer. Significant discrepancy between the intensity of the staining and histological types of ovarian cancer could be established (p<0.01). It is reported for the first time that the expression of mRNA of L-PGDS exists in the ovarian cancer, and is related to the cancer type. This may have significance for the progress of ovarian cancer.
UI - 12032225
AU - Alvi AJ; Hogg R; Rader JS; Kuo MJ; Maher ER; Latif F
TI - Mutation screening analysis of the retinoblastoma related gene RB2/p130 in sporadic ovarian cancer and head and neck squamous cell cancer.
SO - Mol Pathol 2002 Jun;55(3):153-5
AD - Section of Medical and Molecular Genetics, Department of Paediatrics and Child Health, University of Birmingham, Birmingham B15 2TT, UK.
AIMS: To investigate the involvement of the RB2/p130 gene in the pathogenesis of sporadic ovarian cancer in addition to head and neck squamous cell carcinoma (HNSCC). METHODS: Paired tumour and patient matched normal DNA samples from 43 sporadic ovarian tumours and 39 normal/tumour HNSCC DNA samples were screened. The mutation screen used polymerase chain reaction (PCR) amplification followed by single strand conformation polymorphism analysis and direct sequencing of the PCR products. Exons 19 and 20 (B domain) and exons 21 and 22 (C-terminus) were analysed for mutations. These exons were chosen because most of the point mutations in RB2/p130 are located in the C-terminal region and mutations in these exons have been identified previously in nasopharyngeal carcinomas and primary lung tumours. RESULTS: No abnormal band shifts were seen in the samples analysed, and no bands directly sequenced revealed the presence of mutations. CONCLUSIONS: Genetic alterations in the RB2/p130 gene (exons 19-22) are unlikely to be involved directly in the pathogenesis of sporadic ovarian cancer or HNSCC.
UI - 12076210
AU - Seidman JD
TI - Osteopontin as a biomarker for ovarian cancer.
SO - JAMA 2002 Jun 26;287(24):3209; discussion 3209-10
UI - 11373212
AU - Nakamoto Y; Saga T; Ishimori T; Mamede M; Togashi K; Higuchi T; Mandai
TI - M; Fujii S; Sakahara H; Konishi J Clinical value of positron emission tomography with FDG for recurrent ovarian cancer.
SO - AJR Am J Roentgenol 2001 Jun;176(6):1449-54
AD - Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University Hospital, 54 Shogoin-kawahara-cho, Sakyo-Ku, Kyoto, 606-8507 Japan.
OBJECTIVE: Recurrence is often a major problem for patients who have undergone surgery for ovarian cancer. This prospective study was undertaken to evaluate the clinical contribution of positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) for recurrent ovarian cancer. SUBJECTS AND METHODS: Twenty-four women who had undergone surgery or chemoradiotherapy for histopathologically proven ovarian cancer were enrolled in this study. Ovarian cancer was thought to have recurred in 12 of these women because of evidence on conventional imaging modalities or tumor marker measurements (group A). Clinical findings for the remaining 12 women showed them to be disease-free (group B). PET findings for the women were compared with the final diagnoses obtained by histopathology or by clinical follow-up. The clinical contribution of PET was assessed by evaluating whether PET yielded information complementing the findings of conventional modalities and by examining its impact on treatment. RESULTS: PET gave valuable information for seven of 12 patients in group A in addition to the information obtained from findings on conventional imaging, and treatment was affected in five patients. On the other hand, in group B, additional information was obtained in only three of 12 patients, and treatment of only one patient was affected. Overall sensitivity, specificity, and accuracy of conventional imaging modalities were 72.7%, 75.0%, and 73.3%, respectively, and these rates improved to 92.3%, 100.0%, and 94.4%, respectively, by considering both conventional imaging modalities and PET findings. CONCLUSION:Our preliminary data suggest that whole-body PET with FDG can be a complementary modality for following up patients who have had ovarian cancer, especially patients believed to be at risk for recurrence.
UI - 11829055
AU - Bredart A; Autier P; Riccardo A; Audisio A; Geraghty JG
TI - Psychosocial dimensions of BRCA testing: an overshadowed issue.
SO - Eur J Cancer Care (Engl) 2001 Jun;10(2):96-9
AD - Psycho-Oncology Research Unit, European Institute of Oncology, Milan, Italy.
Routine cancer susceptibility testing will soon be feasible in clinical practice. However, to date, this new technology has entailed many limitations, including potential adverse psychosocial consequences. Empirical studies examining these psychosocial aspects are strikingly scarce, especially in continental European countries. Are we prepared for managing the psychosocial problems that emerge from widespread introduction of this practice? Current research do not take into account cross-cultural variations in attitudes and reactions towards genetic testing. This paper points to the urgent need for obtaining a more accurate picture on the psychosocial aspects of breast cancer gene testing and disclosure in order to design recommendations for implementation in populations with highly variable cultural and legal background.
UI - 11798816
AU - Cheng G; Tian F; Li Y
TI - [The selection of taxol resistance associated genes in ovarian cancer cell line by mRNA DD]
SO - Zhonghua Yi Xue Za Zhi 2000 Jul;80(7):541-3
AD - Department of Obstetrics & Gynecology, Chinese PLA General Hospital, Beijing, 100853, China.
OBJECTIVE: One of the main reasons of the treatment failure for ovarian cancer is the emergence of drug resistance in which several genes involved. The purpose of the study was to select the genes related to Taxol resistance in ovarian cancer. METHODS: Resistant ovarian cancer cell line, Skov3/Taxol-25, was established by interval exposure Skov3 to Taxol. mRNA was compared between Skov3 and Skov3/Taxol-25 by mRNA DD. RESULTS: Skov3/Taxol-25 showed 44 times increase resistance to Taxol after 12 months of induction. There were 22 new differential bands obtained from Skov3/Taxol-25 as compared with Skov3. 18 bands were special by repeated PCR. In the 5 sub-clones, three clones were homologous to the known gene. 105/106 base pair of clone 1 were homologous to tPA (tissue plasminogen activator), 261/268 of clone 3 to Kiaa 0372, and 406/409 of clone 18 to LDLC. The other 2 ESTs were new gene segments, which were banked to Genbank with the number of AF120327 and AF120328. The identification by RT-PCR revealed that both tPA and Kiaa0372 were special genes from Skov3/Taxol-25, while LDLC was pseudopositive. CONCLUSION: Several genes were involved in the resistance to Taxol in ovarian cancer. The enhanced expression of tPA indicated the increased ability of metastasis after the acquisition of resistance to taxol.
UI - 12019173
AU - Sawiris GP; Sherman-Baust CA; Becker KG; Cheadle C; Teichberg D; Morin
TI - PJ Development of a highly specialized cDNA array for the study and diagnosis of epithelial ovarian cancer.
SO - Cancer Res 2002 May 15;62(10):2923-8
AD - Laboratory of Cellular and Molecular Biology, Gerontology Research Center, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Ovarian cancer is a major cause of cancer death in women. Unfortunately, the molecular pathways underlying ovarian cancer progression are poorly understood, making the development of novel diagnostic and therapeutic strategies difficult. On the basis of our previous observations obtained from serial analysis of gene expression, we have constructed a specialized cDNA array for the study of ovarian cancer. Small, specialized arrays have several practical advantages and can reveal information that is lost in the "noise" generated by irrelevant genes present in larger arrays. The array, which we named Ovachip, contains 516 cDNAs chosen from our serial analysis of gene expression and cDNA array studies for their relevance to ovarian cancer. The gene expression patterns revealed with the Ovachip are highly reproducible and extremely consistent among the different ovarian specimens tested. This array was extremely sensitive at differentiating ovarian cancer from colon cancer based on expression profiles. The Ovachip revealed clusters of coordinately expressed genes in ovarian cancer. One such cluster, the IGF2 cluster, is particularly striking and includes the insulin-like growth factor II, the cisplatin resistance-associated protein, the checkpoint suppressor 1, the cyclin-dependent kinase 6, and a protein tyrosine phosphatase receptor. We also identified a cluster of down-regulated genes that included the cyclin-dependent kinase 7 and cyclin H. Thus, the Ovachip allowed us to identify previously unidentified clusters of differentially expressed genes that may provide new paradigms for molecular pathways important in ovarian malignancies. Because of the relevance of the arrayed genes, the Ovachip may become a powerful tool for investigators in the field of ovarian cancer and may facilitate progress in understanding the etiology of this disease and in its clinical management.
UI - 12034950
AU - Fenchel S; Grab D; Nuessle K; Kotzerke J; Rieber A; Kreienberg R; Brambs
TI - HJ; Reske SN Asymptomatic adnexal masses: correlation of FDG PET and histopathologic findings.
SO - Radiology 2002 Jun;223(3):780-8
AD - Department of Nuclear Medicine, University of Ulm, Steinhovelstrasse 9, 89075 Ulm, Germany. firstname.lastname@example.org
PURPOSE: To analyze asymptomatic adnexal masses at positron emission tomography (PET) with fluorodeoxyglucose (FDG) in correlation with histopathologic findings and evaluate FDG PET for assessing malignancy in comparison with transvaginal B-mode and Doppler ultrasonography (US) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Ninety-nine patients underwent static FDG PET of the abdomen. US scans were evaluated according to sonomorphologic scoring systems. Resistance index of tumor blood vessels was calculated. Transverse and sagittal T1-weighted MR images obtained before and after intravenous administration of gadopentetate dimeglumine with a fat-saturation technique and T2-weighted MR images were acquired at 1.5 T. Adnexal mass malignancy was first assessed with each modality and then with a combination of the three techniques. Final diagnosis was made with histopathologic evaluation. RESULTS: FDG PET depicted seven of 12 malignant and 66 of 87 benign asymptomatic adnexal tumors. False-negative PET results were obtained in five of seven stage pT1a cystadenocarcinomas and tumors of low malignant potential but not in advanced-stage ovarian carcinomas. Small moderately intense FDG accumulations in the lower pelvis were caused by benign adnexal tumors or gastrointestinal activity in 21 of 27 cases. The overall sensitivities and specificities were 58% (95% CI: 27.7, 84.8) and 76% (95% CI: 65.5, 84.4), respectively, for FDG PET; 92% (95% CI: 61.5, 99.8) and 60% (95% CI: 48.7, 70.1), respectively, for US; 83% (95% CI: 51.6, 97.7) and 84% (95% CI: 74.5, 90.9), respectively, for MR imaging; and 92% (95% CI: 61.5, 99.8) and 85% (95% CI: 75.8, 91.8), respectively, for the combination of three modalities. CONCLUSION: Since the sensitivity of US is as high as that of PET, MR imaging, and the combination of three modalities, it remains the method of choice for diagnosis and assessment of asymptomatic adnexal masses.
UI - 11965197
AU - Friedenson B
TI - A current perspective on genetic testing for breast and ovarian cancer: the oral contraceptive decision.
SO - MedGenMed 2001 Nov 2;3(6):2
AD - Department of Biochemistry and Molecular Biology at the University of Illinois at Chicago, Chicago, Illinois, USA. molmeddoc@Yahoo.com.
A clinician faces a problem in how best to counsel the woman with a family history of breast or ovarian cancer about her options for pregnancy prevention. The physician must guide her as she makes new and complex decisions. Recent data strongly support an amplified effect of the estrogens in oral contraceptives for the woman with a genetic risk for breast cancer. Nonetheless, a woman's immediate need to prevent pregnancy may be much more important to her than worrying about the long-term risk of breast cancer. Another factor is that oral contraceptives prevent ovarian cancer, so the physician may wish to prescribe them to protect her from ovarian cancer. In some genetic backgrounds, however, oral contraceptives not only do not prevent ovarian cancer, but they may raise the risk of breast cancer so significantly that they should not be taken. With other genetic backgrounds, oral contraceptives will protect the woman from ovarian cancer without much effect on her breast cancer risk. When does each of these cancer risks or benefits become significant? The clinician can provide an important benefit to a woman who must prevent pregnancy yet worries about her cancer risk. The physician can help her evaluate the evidence, with its gaps and uncertainties, in the context of her own preferences. To assist in this evaluation, this decision aid provides base-line estimates of the cancer risk that accompanies each of a woman's options. In some cases, genetic testing is likely to provide valuable information as she makes choices about contraception and the risks vs. benefits of different alternatives available to her.
UI - 12047299
AU - Tiitinen A
TI - Hormonal replacement therapy and ovarian cancer.
SO - Acta Obstet Gynecol Scand 2002 Jun;81(6):479-81
AD - Helsinki University Central Hospital, Hus, Finland. email@example.com
UI - 12047311
AU - Kurata H; Takakuwa K; Tsuneki I; Aoki Y; Tanaka K
TI - Ovarian tumor cell detection in peripheral blood progenitor cells harvests by RT-PCR.
SO - Acta Obstet Gynecol Scand 2002 Jun;81(6):555-9
AD - Department of Obstetrics and Gynecology, Faculty of Medicine, Niigata University, Japan. firstname.lastname@example.org
BACKGROUND: To evaluate the frequency of tumor cell contamination in autologous peripheral-blood progenitor cells from patients with ovarian cancer, and to determine the impact of infusing such cells on relapses after high-dose chemotherapy. METHODS: Seventy-three samples of peripheral-blood progenitor cells from 24 ovarian cancer patients were studied for contaminated tumor cells by cytokeratin 7 and cytokeratin 20 reverse transcriptase polymerase chain reaction. RESULTS: Tumor cell contamination in peripheral-blood progenitor cells was detected in 11 of 24 patients (46%) and, among these, in four of 11 patients who received transplantations of peripheral-blood progenitor cells. There was no trend towards longer relapse-free survival in patients infused with cytokeratin-negative peripheral-blood progenitor cells as compared with positive ones. Interestingly, two of four patients who received transplantations of peripheral-blood progenitor cells containing tumor cells were free from progression at 20 and 41 months after transplantation. CONCLUSION: Tumor cell contamination of peripheral-blood progenitor cells was frequently noted by transcriptase polymerase chain reaction in patients with ovarian cancer. The biological and clinical significance of this finding remains to be elucidated.
UI - 12055677
AU - Fujii H; Matsumoto T; Yoshida M; Furugen Y; Takagaki T; Iwabuchi K;
TI - Nakata Y; Takagi Y; Moriya T; Ohtsuji N; Ohtsuji M; Hirose S; Shirai T Genetics of synchronous uterine and ovarian endometrioid carcinoma: combined analyses of loss of heterozygosity, PTEN mutation, and microsatellite instability.
SO - Hum Pathol 2002 Apr;33(4):421-8
AD - Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Synchronous development of carcinomas in the endometrium and ovaries is a fairly common phenomenon, but distinction of a single clonal tumor with metastasis from 2 independent primary tumors may present diagnostic problems. To determine clonality and the occurrence of progression, we microdissected multiple foci from 17 cases of synchronous endometrioid carcinomas and studied loss of heterozygosity (LOH), microsatellite instability (MI), and PTEN mutations. In 14 of the 17 cases, genetic alterations were either homogeneous or found in only some of the foci. LOH was detected for 10q (4 cases), 17p (2 cases), and 2p, 5q, 6q, 9p, 11q, 13q, and 16q (1 case each). Four cases had the MI phenotype with discordant MI patterns between both tumor sites, thus indicating a biclonal or triple clonal process. In 3 of 6 cases with PTEN mutations, identical mutations in both tumor sites indicated a single clonal neoplasm. Altogether, 14 synchronous tumors were genetically diagnosed as follows: single clonal tumor, characterized by concordant genetic alterations in both tumor sites, including identical LOH, identical PTEN mutations, and/or identical sporadic allelic instability patterns (4 cases); single clonal tumor with genetic progression, homogeneous LOH or identical PTEN mutations in both tumor sites and progressive LOH in ovarian metastatic foci (2 cases); and double (7 cases) or triple clonal tumors (1 case), determined by discordant PTEN mutations, heterogeneous LOH, and/or discordant MI patterns. Thus, 35% of synchronous tumors were monoclonal, 47% were polyclonal, and 18% were undetermined. The favorable prognosis of synchronous endometrioid carcinomas may be due to the occurrence of PTEN mutations in both independent and metastatic tumors, the MI-positive independent primary tumors, and the low frequency of LOH. Copyright 2002, Elsevier Science (USA). All rights reserved.
UI - 11822759
AU - Bidoli E; Lavecchia C; Talamini R; Negri E; Parpinel M; Conti E;
TI - Montella M; Carbone MA; Franceschi S Micronutrients and ovarian cancer: a case-control study in Italy.
SO - Ann Oncol 2001 Nov;12(11):1589-93
AD - Servizio di Epidemiologia, Centro di Riferimento Oncologico, Aviano Italy. email@example.com
BACKGROUND: The role of selected micronutrients, vitamins and minerals in the aetiology of epithelial ovarian cancer was investigated using data from a case-control study conducted between 1992 and 1999 in five Italian areas. PATIENTS AND METHODS: Cases were 1,031 patients with histologically confirmed incident epithelial ovarian cancer. Controls were 2,411 subjects admitted for acute, non-neoplastic diseases to major hospitals in the same catchment areas. Dietary habits were elicited using a validated food frequency questionnaire including 78 food groups and recipes. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed by quintiles of intake of nutrients. RESULTS: Inverse associations emerged for vitamin E (OR = 0.6; 95% CI: 0.5-0.8), beta-carotene (OR = 0.8; 95% CI: 0.6-1.0), lutein/zeaxanthin (OR = 0.6; 95% CI: 0.5-0.8 for the highest vs. the lowest quintile of intake), and calcium intake (OR = 0.7; 95% CI: 0.6-1.0). When the combined effect of calcium and vitamin E was considered, the OR reached 0.4 (95% CI: 0.3-0.7) for subjects in the highest compared to those in the lowest intake tertile of both micronutrients. Results were consistent across strata of menopausal status, parity and family history of ovarian or breast cancer. CONCLUSIONS: The intake of selected micronutrients, which were positively correlated to a diet rich in vegetables and fruits, was inversely associated with ovarian cancer.
UI - 12036914
AU - Garner EI; Stokes EE; Berkowitz RS; Mok SC; Cramer DW
TI - Polymorphisms of the estrogen-metabolizing genes CYP17 and catechol-O-methyltransferase and risk of epithelial ovarian cancer.
SO - Cancer Res 2002 Jun 1;62(11):3058-62
AD - Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Because some studies have linked polymorphic variants of the estrogen-metabolizing genes CYP17 and catechol O-methyl transferase (COMT) with risk for hormonally related cancers, we sought to determine whether selected polymorphisms of these genes differed between women with and without ovarian cancer. From a population-based study of ovarian cancer, we analyzed DNA from a total of 480 cases and controls. PCR amplification was performed using primers that amplify restriction sites for MspAI (A2 polymorphism-CYP17) and NlaIII (Val/Met polymorphism-COMT). Digestion of the PCR products was performed. Genotypes identified by gel electrophoresis were assigned as homozygous wild type (WW), heterozygous variant (Wv), and homozygous variant (vv). Frequencies were compared using chi(2) or Fisher's exact tests. Logistic regression was used to calculate crude and adjusted relative risks (RRs) for ovarian cancer associated with possession of any variant allele overall, and within demographic, weight, and smoking history categories, and by histological subtype of ovarian cancer. A portion (68.9%) of cases either carried or was homozygous for the A2 variant of CYP17 compared with 53.9% of controls, for a RR (and 95% confidence interval) of 1.86 (1.26, 2.75; P = 0.003), adjusted for age, parity, oral contraceptive use, site of study, and family history of breast or ovarian cancer. The increased risk was most apparent for women >50 and women with invasive serous cancers. A portion (71.9%) of cases either carried or was homozygous for the Val/Met variant of COMT, compared with 76.9% of controls (P = 0.27). Although the inverse association of ovarian cancer with possession of a Val/Met variant was not significant overall, it was for mucinous tumors of the ovary, with an adjusted RR of 0.28 (0.13, 0.61; P = 0.0012). Possession of the A2 variant of CYP17 appears to increase risk for ovarian cancer, whereas possession of the Val/Met variant of COMT decreases the risk for mucinous tumors. Confirmation in other populations and further exploration of potential pathogenetic mechanisms will be necessary.
UI - 11935694
AU - Ivanov S
TI - [Borderline ovarian tumors]
SO - Akush Ginekol (Sofiia) 2002;42(1):23-5
AD - Gynaecological Clinic, SBALAG-EAD, Sofia.
Forty three patients with borderline ovarian tumours were examined from 1987 till 2000. 28 patients (65.1%) were serous tumours and 15 patients (35%) were mucinous. The median age was 42.2 +/- 15.4 years. The follow-up period was 5.4 +/- 3.2 years. Preoperatively Ca125 were 52.5 +/- 50.3 and of Ca19.9-42.4 +/- 46.8 IU. 83% of the patients were in stage I and 17% in stage III. There was no significant difference in the tumour volumes. Ca125 were significantly increased in the serous tumours and Ca19.9 were increased in the mucinous tumours. All the patients were followed up and are in good health or remission with exception of 2 who developed recurrence.
UI - 11935696
AU - Tomov S; Gorchev G; Tsingilev D; Kurlov A; Kolnova S
TI - [Structure and function of epidermal growth factor receptors and their significance as a prognostic marker in ovarian carcinoma]
SO - Akush Ginekol (Sofiia) 2002;42(1):28-31
UI - 12053288
AU - Nguyen HN
TI - [Tumor risk in Peutz-Jegher's syndrome]
SO - Dtsch Med Wochenschr 2002 Jun 7;127(23):1272-3
AD - Schwerpunkt Gastroenterologie und Stoffwechselkrankheiten, Hubertusstr, Germany.
UI - 12067990
AU - Bayani J; Brenton JD; Macgregor PF; Beheshti B; Albert M; Nallainathan
TI - D; Karaskova J; Rosen B; Murphy J; Laframboise S; Zanke B; Squire JA Parallel analysis of sporadic primary ovarian carcinomas by spectral karyotyping, comparative genomic hybridization, and expression microarrays.
SO - Cancer Res 2002 Jun 15;62(12):3466-76
AD - Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
Analysis of ovarian carcinomas has shown that karyotypes are often highly abnormal and cannot be identified with certainty by conventional cytogenetic methods. In this study, 17 tumors derived from 13 patients were analyzed by a combination of spectral karyotyping (SKY), comparative genomic hybridization (CGH), and expression microarrays. Within the study group, a total of 396 chromosomal rearrangements could be identified by SKY and CGH analysis. When the distribution of aberrations was normalized with respect to relative genomic length, chromosomes 3, 8, 11, 17, and 21 had the highest frequencies. Parallel microarray expression studies of 1718 human cDNAs were used to analyze expression profiles and to determine whether correlating gene expression with chromosomal rearrangement would identify smaller subsets of differentially expressed genes. Within the entire set of samples, microarray expression analysis grouped together poorly differentiated tumors irrespective of histological subtype. For three patients, a comparison between genomic alterations and gene expression pattern was performed on samples of primary and metastatic tumors. Their common origin was demonstrated by the close relationship of both the SKY and CGH karyotypes and the observed profiles of gene expression. In agreement with the pattern of genomic imbalance observed for chromosome 3 in ovarian cancer, the relative expression profile with respect to a normal ovary exhibited a contiguous pattern of reduced expression of genes mapping to the 3p25.5-3p21.31 and increased expression of genes from 3q13.33-3q28. This study demonstrates that SKY, CGH, and microarray analysis can in combination identify significantly smaller subsets of differentially expressed genes for future studies.
UI - 12085231
AU - Ding Z; Zhou JY; Wei WZ; Baker VV; Wu GS
TI - Induction of apoptosis by the new anticancer drug XK469 in human ovarian cancer cell lines.
SO - Oncogene 2002 Jul 4;21(29):4530-8
AD - Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit 48201, USA.
XK469, a synthetic quinoxaline phenoxypropionic acid derivative, has been found to have selective activity against a broad panel of solid tumors including several drug-resistant cell lines and has been approved for phase I clinical evaluation. Recent studies suggested that XK469 is a selective topoisomerase IIbeta inhibitor, but the mechanism of XK469-induced cell death remains unknown. Here we investigate the ability of XK469 to induce apoptosis of human cancer cells. In the human ovarian cancer cell line PA1, XK469 caused the release of cytochrome c, activation of caspases including caspases 9, 7 and 3, cleavage of PARP, and subsequently cell death. Moreover, Bcl2 and Bax were cleaved in XK469 treated cells. PA1 cells expressing the dominant negative-caspase 9 were less sensitive to XK469. Importantly, in these PA1 cells expressing DN-casp 9, the activation of caspases including caspases 3, 7 and 9, and cleavage of Bax and Bcl2 were inhibited, suggesting that the activation of the mitochondrial pathway is required for XK469-induced anticancer activity. These results indicate that the induction of apoptosis by XK469 may account for its anti-tumor activity and such activity is required for the activation of the mitochondrial pathway. Thus, our study defines a possible mechanism, at least in part, underlying XK469-induced anti-cancer activity.
UI - 12054733
AU - Gunthert AR; Grundker C; Hollmann K; Emons G
TI - Luteinizing hormone-releasing hormone induces JunD-DNA binding and extends cell cycle in human ovarian cancer cells.
SO - Biochem Biophys Res Commun 2002 May 31;294(1):11-5
AD - Department of Gynecology and Obstetrics, Georg-August-University, Robert-Koch-Street 40, D-37075 Gottingen, Germany.
Expression of luteinizing hormone-releasing hormone (LHRH) and its receptor as part of an autocrine regulatory system of cell proliferation has been demonstrated in a number of human malignant tumors, including cancers of the ovary. This study was conducted to investigate whether LHRH induces activation of JunD and affects cell cycle regulation and DNA synthesis. Treatment of primary human ovarian cancer cells and human ovarian cancer cell lines EFO-21 and EFO-27 with LHRH agonist triptorelin (100 nM) resulted in an increase in G(0/1) phase and a decrease in G(2/S) phase of cell cycle. Treatment of quiescent EFO-21 or EFO-27 cells with triptorelin (100 nM) resulted in a 46.7 or 44.2-fold increase of AP-1 activation, respectively (p<0.001). Maximal binding of JunD on DNA consensus sequence was found after 4 h of treatment of quiescent EFO-21 or EFO-27 cells with triptorelin (100 nM). DNA synthesis was significantly decreased to 45.5+/-11.4% (day 0=control=100%; p<0.001) after 3 days of triptorelin (1 nM) treatment. These results suggest that LHRH agonist triptorelin induces JunD-DNA binding, resulting in reduced proliferation as indicated by increased G(0/1) phase of cell cycle and decreased DNA synthesis. Since LHRH activates nucleus factor kappa B (NF kappa B) and protects ovarian cancer cells from doxorubicin-induced apoptosis and JunD is shown to decrease cell cycle and cell proliferation, we propose that JunD activated by LHRH acts as a modulator of cell proliferation and cooperates with the anti-apoptotic and anti-mitogenic functions of LHRH.
UI - 12090593
AU - Zanotti KM; Hart WR; Kennedy AW; Belinson JL; Casey G
TI - Allelic imbalance on chromosome 17p13 in borderline (low malignant potential) epithelial ovarian tumors.
SO - Int J Gynecol Pathol 1999 Jul;18(3):247-53
AD - Department of Obstetrics and Gynecology, The Cleveland Clinic Foundation, Ohio 44195, USA.
Borderline epithelial ovarian tumors (BEOTs) possess clinical and pathologic features intermediate between cystadenomas and cystadenocarcinomas. Although the clinical and pathologic characteristics of BEOTs are well described, the molecular aspects are poorly understood. Three regions of loss of heterozygosity (often referred to as allelic imbalance [AI] when identified by polymerase chain reaction) on chromosome 17p13, one of which includes the p53 gene, have been implicated in the development of ovarian and breast cancers. To provide evidence that genes in these regions also may be involved in the development of BEOTs, we undertook a detailed analysis of AI at all three loci in BEOTs from 21 patients. Seventeen of the BEOTs were serous and four were mucinous. Five of 21 tumors (24%) had AI at one or more loci. Four tumors had AI using the D17S695 marker, two of which showed AI only at this locus. In addition, three tumors exhibited AI at the D17S654 locus, one of which showed AI only at this locus. These data suggest that there may be two tumor suppressor genes distal to p53 involved in the development of at least a subset of BEOTs. Peritoneal implants from a subset of serous BEOTs also were evaluated for AI and were found to be concordant with the primary tumor in all cases. Their genetic similarity is consistent with the implantation theory of peritoneal spread of serous BEOTs in these cases.
UI - 12051865
AU - Colgan TJ; Boerner SL; Murphy J; Cole DE; Narod S; Rosen B
TI - Peritoneal lavage cytology: an assessment of its value during prophylactic oophorectomy.
SO - Gynecol Oncol 2002 Jun;85(3):397-403
AD - Department of Laboratory Medicine and Pathology, Mount Sinai Hospital, Toronto, Canada. firstname.lastname@example.org
OBJECTIVE: Prophylactic oophorectomy (PO) is an accepted treatment strategy for women who are at high risk for the development of ovarian carcinoma, particularly women who are BRCA mutation-positive. This study sought to assess the utility of peritoneal lavage cytology at the time of PO in detecting occult malignancy in this group of patients. METHODS: Thirty-five high-risk women, who were not suspected of having any malignancy or ovarian mass, underwent peritoneal lavage at the time of PO. Thirty-one of the thirty-five women had undergone BRCA mutation analysis (BRCA1+, 18; BRCA2+, 10; BRCA-, 3). Intensive histopathologic examination was used in all 35 cases to identify occult carcinoma. Lavage specimens were reviewed for the presence of malignant cells and endosalpingiosis. The cytologic review was conducted without knowledge of either the histopathologic or BRCA results. RESULTS: In 32 of the 35 lavage specimens no malignancy was detected. In the remaining three cases malignant cells were detected; in two of these cases histopathologic examination confirmed an ovarian/tubal occult carcinoma. Two of these women were BRCA1 mutation positive. Endosalpingiosis was detected in the peritoneal lavage specimens of 7 of the 32 cases showing no evidence of malignancy. All of these 7 women were BRCA mutation positive or unknown. CONCLUSION: Peritoneal lavage cytology can detect occult carcinoma at the time of PO and should be performed at PO. The significance of occult carcinoma detected by either histopathologic or cytopathologic examination is uncertain. Whether the prevalence of endosalpingiosis detectable by lavage cytology is increased in BRCA mutation-positive patients requires further study.
UI - 12051869
AU - Levine DA; Federici MG; Reuter VE; Boyd J
TI - Cell proliferation and apoptosis in BRCA-associated hereditary ovarian cancer.
SO - Gynecol Oncol 2002 Jun;85(3):431-4
AD - Gynecology and Breast Research Laboratory, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
OBJECTIVE: The goal was to test the hypothesis that cellular growth properties differ between hereditary and sporadic ovarian cancers. METHODS: Cell proliferation and apoptosis were assessed in 67 tumors associated with deleterious germline BRCA mutations (hereditary) and 69 tumors without BRCA mutations (sporadic). Cell proliferation was evaluated by immunohistochemical analysis of Ki-67 expression, and apoptosis was assessed using a TUNEL assay. RESULTS: The mean number of Ki-67-immunopositive nuclei was significantly higher in ovarian cancers from the hereditary group compared with those from the sporadic group (P = 0.017). Cell proliferation did not differ significantly between BRCA1- and BRCA2-associated hereditary tumors, and apoptosis did not differ significantly between the hereditary and sporadic tumors. CONCLUSION: These data indicate that ovarian carcinomas associated with germline BRCA mutations have a significantly higher growth fraction than sporadic cancers. This property may contribute to an improved response to cytotoxic chemotherapy, partially accounting for the longer recurrence-free interval and overall survival observed in the hereditary group.
UI - 12051879
AU - Anupol N; Ghamande S; Odunsi K; Driscoll D; Lele S
TI - Evaluation of prognostic factors and treatment modalities in ovarian cancer patients with brain metastases.
SO - Gynecol Oncol 2002 Jun;85(3):487-92
AD - Division of Gynecologic Oncology, Department of Surgery, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, New York 14263, USA.
OBJECTIVE: The objective of this study is to evaluate the impact of different clinical variables and treatment modalities on survival in patients with brain metastases from ovarian carcinoma. METHODS: Methods included: (1) retrospective chart review of all patients with ovarian cancer and brain metastases from 1986 to 2000 at Roswell Park Cancer Institute and (2) Medline search was performed to extract data from all published reports with three or more cases of ovarian cancer with brain metastases. Cox regression analysis, Kaplan-Meier test, and log rank test were used to calculate survival and compare the impacts of clinical variables and treatment modalities. RESULTS: Fifteen patients with brain metastases out of 1042 women with ovarian carcinoma were identified from our institution, an incidence of 1.4%. The median time from initial diagnosis to detection of brain metastases was 22 months. Patients who were not treated after brain metastasis had a median survival of 0.5 month versus 6 months with therapy. In the subgroup of patients treated with a combination of radiation, surgery, and chemotherapy, the median survival was 22 months. Literature analysis combined with our data generated 124 patients. The only clinically significant variable impacting survival was the presence or absence of additional distant recurrence with median survivals of 3 and 8 months, respectively (P = 0.005). Among patients who received treatment, the combination of radiation and surgery with or without chemotherapy appears to be beneficial, with a median survival of 20 months (P < 0.001). CONCLUSION: Patients with brain metastases from ovarian cancer without any evidence of disease in other sites appear to benefit from aggressive combined treatment with external radiation and surgery with or without chemotherapy with a median survival of 20 months.
UI - 12076885
AU - Bertone ER; Rosner BA; Hunter DJ; Stampfer MJ; Speizer FE; Colditz GA;
TI - Willett WC; Hankinson SE Dietary fat intake and ovarian cancer in a cohort of US women.
SO - Am J Epidemiol 2002 Jul 1;156(1):22-31
AD - Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. email@example.com
Several studies have suggested that high intake of fats and fat-rich foods may increase the risk of ovarian cancer. The authors examined these relations in the Nurses' Health Study cohort. Dietary intake was assessed in 1980, 1984, 1986, and 1990 by using a self-administered food frequency questionnaire. Food data were used to calculate intake of various fats and fatty acids. For best reflection of long-term intake, an updated, cumulative, averaged measure of fat intake was used to predict incidence of ovarian cancer. Between 1980 and 1996, 301 incident cases of invasive epithelial ovarian cancer were confirmed among the 80,258 participants who completed the baseline food frequency questionnaire. There was no evidence of a positive association between intake of any type of fat and ovarian cancer risk, even after adjustment of fat subtypes for one another. Women in the highest quintile of total fat intake were not at increased risk compared with those in the lowest quintile (multivariate relative risk = 1.03, 95 percent confidence interval: 0.72, 1.45, p for trend = 0.97). Intakes of fat-rich foods were also not appreciably associated with ovarian cancer risk, although an increase in risk with frequent intake of eggs was observed. Overall, results suggest no association between intake of any type of fat and ovarian cancer.
UI - 12096084
AU - Jazaeri AA; Yee CJ; Sotiriou C; Brantley KR; Boyd J; Liu ET
TI - Gene expression profiles of BRCA1-linked, BRCA2-linked, and sporadic ovarian cancers.
SO - J Natl Cancer Inst 2002 Jul 3;94(13):990-1000
AD - Division of Clinical Sciences of the National Cancer Institute, Gaithersburg, MD,USA.
BACKGROUND: Germline mutations in BRCA1 and BRCA2 are responsible for 5%-10% of epithelial ovarian cancers, but the molecular pathways affected by these mutations are unknown. We used complementary DNA (cDNA) microarrays to compare gene expression patterns in ovarian cancers associated with BRCA1 or BRCA2 mutations with gene expression patterns in sporadic epithelial ovarian cancers and to identify patterns common to both hereditary and sporadic tumors. METHODS: Tumor samples from 61 patients with pathologically confirmed epithelial ovarian adenocarcinoma with matched clinicopathologic features were studied, including 18 with BRCA1 founder mutations, 16 with BRCA2 founder mutations, and 27 without either founder mutation (termed sporadic cancers). The cDNA microarrays contained 7651 sequence-verified features. Gene expression data were analyzed with a modified two-sided F test, with P<.0001 considered statistically significant. The expression level of six genes was also studied with reverse transcription-polymerase chain reaction. RESULTS: The greatest contrast in gene expression was observed between tumors with BRCA1 mutations and those with BRCA2 mutations; 110 genes showed statistically significantly different expression levels (P<.0001). This group of genes could segregate sporadic tumors into two subgroups, "BRCA1-like" and "BRCA2-like," suggesting that BRCA1-related and BRCA2-related pathways are also involved in sporadic ovarian cancers. Fifty-three genes were differentially expressed between tumors with BRCA1 mutations and sporadic tumors; six of the 53 mapped to Xp11.23 and were expressed at higher levels in tumors with BRCA1 mutations than in sporadic tumors. Compared with the immortalized ovarian surface epithelial cells used as reference, several interferon-inducible genes were overexpressed in the majority of tumors with a BRCA mutation and in sporadic tumors. CONCLUSIONS: Mutations in BRCA1 and BRCA2 may lead to carcinogenesis through distinct molecular pathways that also appear to be involved in sporadic cancers. Sporadic carcinogenic pathways may result from epigenetic aberrations of BRCA1 and BRCA2 or their downstream effectors.
UI - 12117706
AU - Goodman MT; Wu AH; Tung KH; McDuffie K; Kolonel LN; Nomura AM; Terada K;
TI - Wilkens LR; Murphy S; Hankin JH Association of dairy products, lactose, and calcium with the risk of ovarian cancer.
SO - Am J Epidemiol 2002 Jul 15;156(2):148-57
AD - Cancer Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA. firstname.lastname@example.org
Epidemiologic findings have been inconsistent regarding the association of dietary fat, dairy products, and lactose with risk of ovarian cancer. The authors conducted a case-control study in Hawaii and Los Angeles, California, to examine several dietary hypotheses regarding the etiology of ovarian cancer in a population with a broad range of dietary intakes. A total of 558 patients with ovarian cancer diagnosed in 1993-1999 and 607 controls were interviewed regarding their diet. Consumption of all dairy products, all types of milk, and low-fat milk, but not consumption of whole milk, was significantly inversely related to the odds of ovarian cancer. Similar inverse gradients in the odds ratios were obtained for intakes of lactose and calcium, although these nutrients were highly correlated (r = 0.77). The odds ratio for ovarian cancer was 0.46 (95% confidence interval: 0.27, 0.76) among women in the highest quartile of dietary calcium intake versus the lowest (p for trend = 0.0006). The significant dietary association was limited to dairy sources of calcium (p for trend = 0.003), although a nonsignificant inverse gradient in risk was also found in relation to calcium supplement intake. These results suggest that intake of low-fat milk, calcium, or lactose may reduce the risk of ovarian cancer.