National Cancer Institute®
Last Modified: August 1, 2002
UI - 12112655
AU - Yazici H; Glendon G; Yazici H; Burnie SJ; Saip P; Buyru F; Bengisu E;
TI - Andrulis IL; Dalay N; Ozcelik H BRCA1 and BRCA2 mutations in Turkish familial and non-familial ovarian cancer patients: a high incidence of mutations in non-familial cases.
SO - Hum Mutat 2002 Jul;20(1):28-34
AD - Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, and Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Canada.
Ovarian cancer is a clinically important cancer in Turkey. The contribution of BRCA1 and BRCA2 to ovarian cancer in Turkish patients has not previously been described. In this study we investigated the presence of BRCA1 and BRCA2 mutations in 102 consecutively ascertained, hospital-based, ovarian cancer cases. Four out of 15 (26.7%, 95% confidence interval (CI), 7.8%-55.1%) familial cases were found to carry mutations in BRCA1. Thirteen of the 87 (14.9%, 95% CI, 7.5%-22.4%) non-familial cases had BRCA1 and BRCA2 mutations, six in BRCA1, and seven in BRCA2. We have further studied the non-familial ovarian cancer cases to determine which subgroups have a likelihood of carrying clinically important mutations. Our study shows that those Turkish ovarian cancer patients with serous histopathology harbor a high proportion of mutations (12/58, 20.7%, 95% CI, 10.3%-31.1%) compared to all non-familial cases (14.9%) regardless of pathology. Within the serous sub-group, those that were also diagnosed below age 50 have an even greater percentage of mutations (8/28, 28.6%, 95% CI, 11.8%-45.3%). Our findings demonstrate that a substantial proportion of Turkish ovarian cancer patients, both with and without a family history, carry BRCA1 and BRCA2 mutations, demonstrating the importance of BRCA1 and BRCA2 in the development of ovarian cancer in this population. Copyright 2002 Wiley-Liss, Inc.
UI - 12142397
AU - Nekulova M; Pecen L; Kalabova R; Simickova M; Topolcan O; Pikner R;
TI - Vondracek V; Valik D Predicting response of ovarian cancer to paclitaxel treatment based on trend analysis of serum CA125.
SO - Clin Chem 2002 Aug;48(8):1364-7
AD - Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 65 Brno, The Czech Republic.
UI - 12115565
AU - Obermair A; Schmid BC; Packer LM; Leodolter S; Birner P; Ward BG;
TI - Crandon AJ; McGuckin MA; Zeillinger R Expression of MUC1 splice variants in benign and malignant ovarian tumours.
SO - Int J Cancer 2002 Jul 10;100(2):166-71
AD - Queensland Centre for Gynaecological Cancer, Royal Brisbane Hospital, Brisbane, Australia. email@example.com
MUC1 is expressed on the surface of ovarian cancer cells. Nine different splice variants of MUC1 have been described, but no study has reported on the expression of MUC1 isoforms in human ovarian cancer. Our study compares patterns of expression of MUC1 splice variants of malignant and benign ovarian tumours. Ovarian tissue samples were taken from patients with benign ovarian tumours (n = 34) and from patients who had surgery for primary (n = 47) or recurrent (n = 8) ovarian cancer. RT-PCR for MUC1 splice variants A, B, C, D, X, Y, Z, REP and SEC was performed and their expression compared to clinical and histopathologic parameters. Variants A, D, X, Y and Z were more frequently expressed in malignant than in benign tumours. All primary ovarian cancer cases were positive for variant REP but negative for variant SEC. No significant association of the expression of MUC1 splice variants with the response to chemotherapy or patient survival could be demonstrated. Expression of MUC1 splice variants A, D, X, Y, Z and REP is associated with the presence of malignancy, whereas expression of MUC1/SEC is associated with the absence of malignancy. Copyright 2002 Wiley-Liss, Inc.
UI - 11843247
AU - Campos B; Diez O; Domenech M; Baena M; Pericay C; Balmana J; del Rio E;
TI - Sanz J; Alonso C; Baiget M BRCA2 mutation analysis of 87 Spanish breast/ovarian cancer families.
SO - Ann Oncol 2001 Dec;12(12):1699-703
AD - Servei de Genetica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
BACKGROUND: It is estimated that about 5% -10% of breast cancer (BC) cases is due to inherited predisposition. Early works reported that 45%-50% of site-specific BC families had BRCA1 mutations and 25%-35% BRCA2 mutations. However, these percentages could have been overestimated and likely vary among the populations studied. PATIENTS AND METHODS: We analysed the BRCA2 gene in 87 Spanish breast/ovarian cancer families in which the BRCA1 mutation screening was negative. RESULTS: We detected 15 (17.2%) disease-causing mutations and 11 polymorphisms and unclassified variants. Four mutations were recurrent, and five were novel. Seven (47%) mutations were found in site-specific female BC families, five (33%) in families with OC cases, and three (20%) mutations in families with male BC cases. There was incomplete penetrance of the mutations in some families, and considerable phenotypic variations with respect to the age of diagnosis and cancer types. CONCLUSIONS: The percentage of mutations detected reinforces the possibility that some of these families have mutations in genes other than BRCA1 or BRCA2 that confer lower BC risks.
UI - 12117191
AU - Barakat RR; Hricak H
TI - What do we expect from imaging?
SO - Radiol Clin North Am 2002 May;40(3):521-6, vii
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. firstname.lastname@example.org
The objectives of imaging in gynecologic cancer include tumor detection, tumor diagnosis, staging, and follow-up. In addition, both monitoring response to treatment and differentiating tumor recurrence from post-treatment changes are important indications for imaging. In 2001 it was estimated that there would be 38,300 cases of endometrial cancer, 23,400 cases of ovarian cancer, and 12,900 cases of cervical cancer. This article reviews what information is required by the practicing gynecologist or gynecologic oncologist prior to surgery and briefly summarizes state-of-the-art imaging in answering clinically pertinent questions.
UI - 12117196
AU - Coakley FV
TI - Staging ovarian cancer: role of imaging.
SO - Radiol Clin North Am 2002 May;40(3):609-36
AD - Department of Radiology, University of California San Francisco, 94143, USA. Fergus.Coakley@radiology.ucsf.edu
Ovarian cancer is relatively common, and often presents at an advanced stage with widespread intraperitoneal metastases. The constellation of complex pelvic masses, ascites, omental cake, and other peritoneal implants is virtually diagnostic. All patients are potential surgical candidates, since suspected early stage disease is treated by a comprehensive staging laparotomy including total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Operable advanced disease is treated by surgical debulking and adjuvant combination chemotherapy. The role of imaging is to detect and characterize adnexal masses as likely malignant, recognize unusual findings that may suggest atypical pathology, demonstrate metastases in order to prevent under-staging, and detect specific sites of disease that may be unresectable. These aims are directly related to clinical management; characterization of an adnexal mass as malignant guides appropriate surgical referral, recognition of atypical pathology such as malignant granulosa cell tumor in a young woman may be an indication for fertility-preserving surgery. Demonstration of metastatic site-assists surgical planning, and detection of unresectable disease may be an indication for neoadjuvant (ie, preoperative) chemotherapy with interval debulking rather than primary debulking with adjuvan (postoperative) chemotherapy.
UI - 12130439
AU - Cho SM; Ha HK; Byun JY; Lee JM; Kim CJ; Nam-Koong SE; Lee JM
TI - Usefulness of FDG PET for assessment of early recurrent epithelial ovarian cancer.
SO - AJR Am J Roentgenol 2002 Aug;179(2):391-5
AD - Department of Radiology, College of Medicine, The Catholic University of Korea, Seocho-Ku, Seoul, South Korea.
OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of FDG positron emission tomography (PET) in comparison with CT in detecting recurrent ovarian carcinoma and its ability to reveal small tumor recurrence. MATERIALS AND METHODS: We reviewed the records of 31 consecutive patients with pathologically proven epithelial carcinoma who underwent FDG PET 1 month before second-look surgery to assess recurrent tumor. Of these 31 patients, 21 patients also underwent CT 1 month before second-look surgery. The diagnostic accuracies of FDG PET (n = 31), CT (n = 21), and combined FDG PET and CT (n = 21) in detecting recurrent tumor were calculated and compared with each other using the Bennett's test in 21 patients who underwent both imaging studies. Detection rates of individual tumors relative to their sizes were compared between FDG PET and CT using the McNemar test. RESULTS: The sensitivity, specificity, and accuracy of FDG PET, CT, and combined FDG PET and CT for revealing recurrent ovarian cancer were 45.3%, 99.7%, 91.0%; 54.5%, 99.6%, 91.7%; 58.2%, 99.6%, 92.4%, respectively. We found no statistically significant difference in the diagnostic accuracy of FDG PET, CT, and combined FDG PET and CT (chi(2) < 5.991). Detection rates of tumor nodules found on CT were significantly greater than those on FDG PET when nodule size was 0.3-0.7 cm (p < 0.05). CONCLUSION: FDG PET did not improve the overall diagnostic accuracy in detecting recurrent ovarian carcinoma compared with CT. Rather, FDG PET was inferior to CT in its ability to reveal small-tumor recurrence.
UI - 11948120
AU - Oberst MD; Johnson MD; Dickson RB; Lin CY; Singh B; Stewart M; Williams
TI - A; al-Nafussi A; Smyth JF; Gabra H; Sellar GC Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor clinicopathological parameters.
SO - Clin Cancer Res 2002 Apr;8(4):1101-7
AD - Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
PURPOSE: Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of ovarian cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase, and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), in epithelial ovarian cancer and to assign clinicopathological correlations. EXPERIMENTAL DESIGN: We have determined by immunohistochemistry the expression of matriptase and HAI-1 in 54 epithelial ovarian cancers. Statistical analyses of immunohistochemistry expression data with clinical outcome and clinicopathological parameters were then performed. RESULTS: Of 54 tumors tested, 39 (72%) and 11 (20%) were positive for matriptase and for HAI-1, respectively. All HAI-1-positive tumors were also matriptase positive. Analysis of clinicopathological parameters demonstrated a loss of matriptase associated with stage III/IV tumors as compared with stage I/II tumors (P = 0.030). There was also a loss of HAI-1 expression associated with stage III/IV tumors (P = 0.039). Of 34 stage I/II tumors, 28 (82%) stained positive for matriptase, and 10 (29%) stained positive for HAI-1; 10 (29%) tumors showed coexpression. Of 20 stage III/IV tumors, however, 11 stained positive for matriptase (55%), only 1 of which coexpressed HAI-1 (P = 0.039). CONCLUSIONS: Advanced-stage ovarian tumors that express matriptase are more likely to do so in the absence of its inhibitor, HAI-1, indicating that an imbalance in the matriptase:HAI-1 ratio could be important in the development of advanced disease. Such an imbalance could promote the proteolytic activity of matriptase and, consequently, a more invasive phenotype.
UI - 11948121
AU - Milliken D; Scotton C; Raju S; Balkwill F; Wilson J
TI - Analysis of chemokines and chemokine receptor expression in ovarian cancer ascites.
SO - Clin Cancer Res 2002 Apr;8(4):1108-14
AD - Cancer Research UK Translational Oncology Laboratory, St. Bartholomew's and the London, Queen Mary's School of Medicine and Dentistry, John Vane Science Centre London, United Kingdom.
PURPOSE: Ascitic disease is a common occurrence in human ovarian cancer, but it is unclear how the cellular composition of ascitic fluid is determined. Because chemokines can determine host cell infiltration in solid ovarian cancer, we assessed CC chemokine protein and CC chemokine receptor expression in ovarian cancer ascites. EXPERIMENTAL DESIGN: We used reverse transcription-PCR and RNase protection assay to determine CC chemokine and chemokine receptor mRNA expression and ELISA to measure CC chemokine protein levels. Flow cytometry was used to identify cell populations and their chemokine receptor protein expression. RESULTS: mRNA for the CC chemokines CCL2, -3, -4, -5, -8, and -22 was expressed in cell isolates from ascites samples, and the corresponding proteins were detected in ascitic fluid. mRNA for CC chemokine receptors CCR1, -2a, -2b, -3, -4, -5, and -8 was detected in cells from ascites. Fluorescence-activated cell-sorting analysis showed variable numbers of macrophages and CD3(+) T lymphocytes (predominantly CD4(+)) within ovarian cancer ascites. CD14(+) macrophages within ascites consistently expressed protein for CCR1, -2, and -5. CCR1 was expressed by >60% of all T cells, but more CD4(+) than CD8(+) T cells expressed CCR2 and -5. A direct correlation was found between the CCL5 concentration and CD3(+) T-cell infiltration. CONCLUSIONS: We conclude that there is a complex chemokine/chemokine receptor network in ovarian cancer ascites. However, associations between chemokine receptor expression, chemokine levels, and cell counts were limited.
UI - 11948100
AU - Young-McCaughan S; Rich IM; Lindsay GC; Bertram KA
TI - The Department of Defense Congressionally Directed Medical Research Program: innovations in the federal funding of biomedical research.
SO - Clin Cancer Res 2002 Apr;8(4):957-62
AD - United States Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, Fort Detrick, Maryland 21702-5024, USA.
In response to the lobbying efforts of the women's advocacy movement, in 1993 Congress authorized funds for a substantial increase in support of new and promising research aimed at the eradication of breast cancer. This appropriation resulted in a major expansion of the United States Army Medical Research and Materiel Command, Department of Defense Breast Cancer Research Program. The Office of Congressionally Directed Medical Research Programs was established within the United States Army Medical Research and Materiel Command to facilitate the management of the expanded extramural research program. Since that time, the programs have grown to include not just breast cancer but also prostate cancer, ovarian cancer, and neurofibromatosis. The unique appropriations to the Office of Congressionally Directed Medical Research Programs has resulted in a number of programmatic innovations. These include development of unique mechanisms of grant support, inclusion of consumer advocates on peer and programmatic review panels, and the introduction of criteria-based evaluation and scoring in peer review. This article describes these novel scientific management strategies and outlines their success in meeting program visions and goals.
UI - 12086867
AU - Daly MB; Ozols RF
TI - The search for predictive patterns in ovarian cancer: proteomics meets bioinformatics.
SO - Cancer Cell 2002 Mar;1(2):111-2
AD - Division of Population Science, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA. email@example.com
Proteomic patterns in serum that discriminate between malignant and benign ovaries may provide a powerful tool for screening in high risk women.
UI - 12113075
AU - Cannon MJ; O'Brien TJ; Underwood LJ; Crew MD; Bondurant KL; Santin AD
TI - Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer.
SO - Expert Rev Anticancer Ther 2002 Feb;2(1):97-105
AD - Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA. firstname.lastname@example.org
Identification of tumor-specific target antigens has been a major hurdle for the treatment of malignant disease by vaccination or immunotherapy. A second challenge has been the induction of therapeutically effective immune responses to these 'self' antigens. The recent recognition of dendritic cells as powerful antigen-presenting cells capable of inducing primary T-cell responses in vitro and in vivo--in combination with identification of tumor-specific antigens--has generated widespread interest in dendritic cell-based immunotherapy against a wide variety of tumors. In this review, a series of recently identified novel ovarian tumor antigens is discussed, and the potential for therapeutic dendritic cell vaccination targeted against these antigens is assessed.
UI - 12112530
AU - Denison SR; Becker NA; Ferber MJ; Phillips LA; Kalli KR; Lee J; Lillie
TI - J; Smith DI; Shridhar V Transcriptional profiling reveals that several common fragile-site genes are downregulated in ovarian cancer.
SO - Genes Chromosomes Cancer 2002 Aug;34(4):406-15
AD - Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Previous transcriptional profiling analysis of 14 primary ovarian tumors identified approximately 12,000 genes as decreased in expression by at least twofold in one or more of the tumors sampled. Among those genes were several known to be mapped to common fragile sites (CFSs), some of which had previously been shown to exhibit a loss of expression in ovarian carcinoma. Therefore, we selected a subset of genes to determine whether they localized within CFSs. Of the 262 genes that were downregulated at least twofold in 13 of 14 tumors, 10 genes were selected based on the following criteria: localization to a CFS band; documented aberrations in at least one malignancy; and feasibility of scoring breakage at the specific CFS. Fluorescence in situ hybridization analysis was performed using bacterial artificial chromosome clones encompassing portions of the genes to determine the position of the genes relative to their corresponding CFSs. Nine genes were determined to localize within seven previously uncloned CFSs. Semiquantitative reverse-transcription/polymerase chain reaction analysis of the cell lines and primary ovarian tumors validated the downregulation of seven of the 10 genes. We identified portions of seven uncloned CFSs and provide data to suggest that several of the genes mapping within CFSs may be inactivated in ovarian cancer. Copyright 2002 Wiley-Liss, Inc.
UI - 12124354
AU - Chan KY; Ozcelik H; Cheung AN; Ngan HY; Khoo US
TI - Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer.
SO - Cancer Res 2002 Jul 15;62(14):4151-6
AD - Department of Pathology, Queen Mary Hospital and the University of Hong Kong, Hong Kong.
Hypermethylation of the BRCA1 promoter has previously been shown to cause reduced mRNA expression in both breast and ovarian cancers. Nothing is yet known of the expression pattern or methylation status of the promoter region of BRCA2 in sporadic ovarian cancer. Whereas our analysis of 30 sporadic ovarian carcinomas showed a statistically significant reduction of BRCA1 mRNA expression (P = 0.001), it also showed, in contrast, overexpression of BRCA2 mRNA (P = 0.002) in tumor compared with nontumor. Hypermethylation of the BRCA1 promoter highly correlated with decreased BRCA1 expression (P = 0.017). Methylated CpGs at the BRCA2 promoter were either absent or at very low levels in tumor DNA, whereas they were present at high levels in nontumor DNA. Such hypomethylation also correlated with elevated levels of BRCA2 mRNA (P = 0.043) and showed a statistically significant correlation with tumor stage (P = 0.037). This supports the role of methylation in BRCA2 contributing to the pathogenesis of sporadic ovarian cancer. Furthermore, 14 (58.2%) and 9 (56.3%) of all of the cases with aberrant BRCA mRNA expression and methylation patterns, respectively, demonstrated opposing mRNA expression and methylation patterns of the BRCA1 and BRCA2 genes within the same cases. Our findings suggest that both genes may be involved in the development of sporadic ovarian cancer.
UI - 11465542
AU - Pieretti M; Khattar NH; Smith SA
TI - Common polymorphisms and somatic mutations in human base excision repair genes in ovarian and endometrial cancers.
SO - Mutat Res 2001 Jan;432(3-4):53-9
AD - Department of Pathology, University of Kentucky, Lexington 40536, USA. email@example.com
The purpose of this study was to determine whether the human APEX and OGG1 genes, encoding proteins important in base excision repair (BER) of DNA, contain nucleotide sequence polymorphisms or are mutated somatically in tumors from women diagnosed with ovarian or endometrial cancer. Based upon the analysis of germline DNA from 83 individuals, 63 with ovarian cancer and 20 with endometrial cancer, we found two missense polymorphisms in APEX (Q51H and D 148E) and two missense (A3P and S326C) and one intronic (Exon 5-15 bp) polymorphism in OGG1. The frequencies of the various alleles (in the ovarian and endometrial cancer patients combined) were 4.8% for 51-His and 56.2% for 148-Glu in APEX, and 1.0% for 3-Pro and 20.0% for 326-Cys in OGG1. Somatic mutations in APEX (P112L, W188X and R237C) were identified in three of 20 endometrial tumors, but no mutations were identified in APEX in 43 ovarian tumors, or in OGG1 at either tumor site. Given the crucial role of the APEX and OGG1 proteins in BER of oxidative DNA damage, the identified polymorphisms are good candidates for genetic epidemiologic studies of cancer susceptibility, while the finding that three of 20 (15%) endometrial tumors have somatic mutations in APEX suggests that inactivation of the BER pathway is important for the development of endometrial cancer in at least a subset of cases.
UI - 11874075
AU - Cherchi PL; Marras V; Capobianco G; Ambrosini G; Piga M; Fadda GM;
TI - Dessole S Immunohistochemical evaluation of a new epithelial antigen, Ber-EP4, in ovarian cancer: preliminary results.
SO - Eur J Gynaecol Oncol 2001;22(6):433-5
AD - Department of Pharmacology, Gynaecology and Obstetrics, University of Sassari, Italy.
OBJECTIVE: To assess the immunohistochemical expression of Ber-EP4, a new epithelial antigen in ovarian cancer. METHODS: We studied 25 cases of ovarian cancer in which Ber-EP4, CEA and CA 125 were investigated by an immunohistochemical method. We evaluated the correlations between immunohistochemical positivity and grading, histotype and stage of disease. RESULTS: CEA was positive in 5 out of 25 cases (20%), CA-125 in 17 out of 25 cases (68%) and Ber-EP4 in 14 out of 25 cases (56%). Ber-EP4 was mainly present in mucinous tumors in comparison to serous tumors (78.6% vs. 50%). Ber-EP4, as well as CA-125, were directly proportional to tumor differentation (70% of positivity in G1 vs 37.5% in G3 for the former and 80% in G1 vs 50% in G3 for the latter, respectively), whereas CEA showed no relevant difference regarding the grading. There were no differences among the three antigens studied with regard to clinical stage. CONCLUSIONS: In our study Ber-EP4 was positive in 14 out of 22 cases (63.6%) of the primary epithelial ovarian cancers studied. The presence of this antigen seems to be related to histotype and grading but not to clinical stage.
UI - 12078339
AU - Cianti C
TI - [Treatment of ovarian cancer]
SO - Clin Ter 2002 Mar-Apr;153(2):135-44
AD - Ospedale S. Spirito in Sassia, Roma, Italia.
PURPOSE: To present an approach to the treatment of epithelial ovarian cancer. DESIGN: A large number of studies in ovarian cancer have been reviewed. RESULTS: Ovarian cancer is the most common fatal malignancy of the female genital tract. The high mortality is due to the fact that the most part of patients are diagnosed with advanced disease. Cytoreductive surgery followed by platinum-based chemotherapy is the standard therapeutic strategy for patients with advanced ovarian cancer. Postsurgical residual disease is the most important prognostic factor. The combination of Paclitaxel and Cisplatin or Carboplatin is currently accepted as the standard chemotherapy for advanced ovarian cancer. Second- look laparatomy should be reserved to patients enrolled in clinical trial. Resistant disease remain the major cause of relapse and death. Several drugs have been employed in second-line therapy; however, the responses are generally short and survival is poor. CONCLUSIONS: Future research should include new drugs or new combination regimens to improve clinical outcomes and overall survival.
UI - 12094103
AU - Modugno F; Ness RB; Cottreau CM
TI - Cigarette smoking and the risk of mucinous and nonmucinous epithelial ovarian cancer.
SO - Epidemiology 2002 Jul;13(4):467-71
AD - Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 516A Parran Hall, 130 DeSoto Street, Pittsburgh, PA 15261, USA. firstname.lastname@example.org
BACKGROUND: The association between cigarette smoking and ovarian cancer may vary according to the histologic type of tumor. METHODS: We examined cigarette smoking as a risk factor for both mucinous and nonmucinous tumors in a population-based case-control study comparing 767 incident cases of epithelial ovarian cancer with 1,367 community controls frequency matched to cases by age and race. RESULTS: Smoking was associated with mucinous tumors (odds ratio [OR] = 1.9; 95% confidence interval [CI] = 1.3-2.9) but not with nonmucinous tumors (OR = 1.1; CI = 0.9-1.3). Furthermore, the odds ratios for smokers with mucinous tumors increased with increasing pack-years of smoking (OR = 1.0, 1.9, and 2.7 for <5, 5-24, and > 24+ pack-years, respectively; P for trend = 0.01) CONCLUSIONS: Cigarette smoking appears to be a risk factor for mucinous but not for nonmucinous tumors.
UI - 12124814
AU - de la Hoya M; Sulleiro S; Osorio A; Diez O; Baiget M; Benitez J;
TI - Diaz-Rubio E; Caldes T Clustering of cancer-related mutations in a subset of BRCA1 alleles: a study in the Spanish population.
SO - Int J Cancer 2002 Aug 10;100(5):618-9
AD - Laboratory of Molecular Oncology, Hospital Universitario San Carlos, Madrid, Spain.
We have observed that the frequency of D17S855 short alleles (139 bp and 141 bp) in individuals carrying BRCA1 germline mutations is higher than in controls (54% vs. 31%, p = 0.0004). By unambiguously establishing mutation/D17S855 phase in 18 BRCA1-positive families, we find that most (11 of 15 different mutations) BRCA1 defects are linked to chromosomes with short alleles (OR = 8.21, 95% CI 1.97-39.32, p = 0.0007). We suggest that BRCA1 mutations are not randomly distributed but clustered in a subset of BRCA1 alleles that can be identified by D17S855 genotyping. Further analysis involving a larger set of mutations and different populations are needed to clarify the relevance of this unexpected finding. Copyright 2002 Wiley-Liss, Inc.
UI - 12146025
AU - Longatto Filho A; Alves VA; Kanamura CT; Nonogaki S; Bortolan J;
TI - Lombardo V; Bisi H Identification of the primary site of metastatic adenocarcinoma in serous effusions. Value of an immunocytochemical panel added to the clinical arsenal.
SO - Acta Cytol 2002 Jul-Aug;46(4):651-8
AD - Pathology Division, Alfredo Lutz Institute. email@example.com
OBJECTIVE: To use an immunocytochemical panel as ancillary method to identify the origin of adenocarcinomas in serous effusions. STUDY DESIGN: Serous effusion samples examined cytologically in the Department of Surgical Pathology, A. C. Camargo Hospital, between 1966 and 1990, were investigated. Of 4,297 cases, 2,317 were associated with adenocarcinoma, and 1,099 were positive for adenocarcinoma by cytologic examination. We selected a total of 248 cases of different origins to subject to immunoreactions. A panel composed of CA-125, CA-19.9, HBME-1, lactoferrin and BRST 2 was tested for the efficiency of these antibodies under two conditions: the panel alone and associated with clinical data, such as anatomic localization of the effusion (pleural or ascitic) and patient sex and age. RESULTS: BRST 2 and lactoferrin were both positive in 29.9% of cases of adenocarcinoma of breast origin; CA-125 and HBME-1 were 28.6% and 25.0% positive in cases of adenocarcinoma of the ovaries, respectively. These immunoreactivities were highly specific when compared to the others. The statistical significance of the results was improved by information on the anatomic location of the effusions and patient sex. CONCLUSION: Our data strongly indicate that BRST 2 and lactoferrin are important components of an immunocytochemical panel used to identify carcinomas of breast origin. Similarly, CA-125 and HBME-1 may be useful in suggesting the ovaries as possible primary sites.
UI - 12126844
AU - Elwood M
TI - Proteomic patterns in serum and identification of ovarian cancer.
SO - Lancet 2002 Jul 13;360(9327):170; discussion 170-1
UI - 12082292
AU - Davidson B
TI - Ovarian carcinoma and serous effusions. Changing views regarding tumor progression and review of current literature.
SO - Anal Cell Pathol 2001;23(3-4):107-28
AD - Department of Pathology, The Norwegian Radium Hospital University of Oslo, Montebello, N-0310 Oslo, Norway. firstname.lastname@example.org
Carcinoma of the ovary is the leading cause of death from gynecological cancer in western countries. Ovarian carcinoma is commonly associated with the accumulation of fluid containing malignant cells in the peritoneal, and not infrequently in the pleural cavity. The differentiation of these cells from reactive mesothelial cells is at times difficult. In addition, tumor progression in ovarian carcinoma and the biological characteristics of carcinoma cells in effusions compared to their counterparts in solid tumors are poorly understood. This review details the current knowledge regarding diagnostic and biologic aspects of effusion cytology, with emphasis on ovarian carcinoma. Results from our first studies of effusions are subsequently presented. These attempt to address several issues. First, to improve the diagnostic ability to detect cancer cells in effusions using antibodies designed for the differentiation of epithelial cells from mesothelial cells. Secondly, to study genotypic and phenotypic differences between ovarian carcinoma cells in effusions, solid primary tumors and metastatic lesions, as well as to compare malignant cells in peritoneal and pleural effusions. These studies of carbohydrate antigens, E-cadherin complex and matrix metalloproteinases (MMP) attempted to evaluate whether ovarian carcinoma cells in effusions possess true metastatic properties, or are similar to the cells in primary tumors, thereby merely representing the result of a shedding process. Finally, the prognostic role of these molecules was studied in solid tumors from a patient cohort consisting of long- and short-term survivors, followed for up to 20 years. Figure 1 on http://www.esacp.org/acp/2001/23-3,4/davidson.htm.
UI - 11938448
AU - Nedelcu R; Liede A; Aube J; Finch A; Kwan E; Jack E; Narod SA; Randall
TI - S; Hugel L; Clark K BRCA mutations in Italian breast/ovarian cancer families.
SO - Eur J Hum Genet 2002 Feb;10(2):150-2
UI - 12124496
AU - Trabelsi A; Conan-Charlet V; Lhomme C; Morice P; Duvillard P; Sabourin
TI - JC [Peritoneal glioblastoma: recurrence of ovarian immature teratoma (report of a case)]
SO - Ann Pathol 2002 Apr;22(2):130-3
AD - Service d'Anatomie et Cytologie pathologiques, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
Immature teratomas of the ovary represent less than 1% of all ovarian teratomas. They contain several tissues that derive from the three embryological layers: ectoderm, mesoderm and endoderm. They are rarely associated with peritoneal implants that are essentially composed of mature glial tissue, and of benign evolution. We report the case of a 37-year- old woman who presented an immature teratoma of the right ovary that recurred seven years later as a malignant neuroepithelial peritoneal tumor resembling a glioblastoma. Glioblastoma was diagnosed at a second recurrence six months later. We discuss the histopathogenesis of peritoneal implants secondary to immature teratomas.
UI - 12144815
AU - Sit AS; Modugno F; Weissfeld JL; Berga SL; Ness RB
TI - Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma.
SO - Gynecol Oncol 2002 Aug;86(2):118-23
AD - Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15213, USA.
OBJECTIVE: Hormone replacement therapy (HRT) has been inconsistently linked to ovarian cancer. Estrogen formulations in HRT vary in their effects on estrogen-sensitive target tissues, such as the ovary. The aim of the study is to evaluate the impact of various HRT formulations and their characteristics of use on the risk of epithelial ovarian carcinoma (EOC). METHODS: We assessed the association between the use of HRT and the risk of invasive EOC in women participating in a population-based, case-control study conducted in the Delaware Valley from 1994 to 1998. Cases aged 45 or above at diagnosis (n = 484) were compared to community controls (n = 926) frequency matched by age and area of residence. Information on HRT formulation, timing, and duration were obtained by in-person interview by trained interviewers. HRT formulations were classified as opposed (estrogen + progestin) or unopposed (estrogen alone). They were further categorized according to the estrogen component as either conjugated equine estrogen (CEE), the most common formulation, or non-CEE. Multivariate unconditional logistic regression analyses were used to adjust for age at diagnosis, number of live births, use of oral contraceptives, family history of ovarian carcinoma, and history of tubal ligation. RESULTS: Overall, no association was found between any use of HRT and EOC. Although use of unopposed non-CEE was associated with a significant decrease in risk among hysterectomized women (OR = 0.17, 95% CI = 0.04,0.82), this was not true for women with an intact uterus (OR = 1.14, 95% CI = 0.44,2.98; P for interaction = 0.049). No significant differences in EOC risk were observed for other HRT formulations. CONCLUSIONS: Our results did not suggest any consistent pattern of altered risk for EOC and the overall use of HRT by specific formulations of HRT.
UI - 12144816
AU - Aktas D; Guney I; Alikasifoglu M; Yuce K; Tuncbilek E; Ayhan A
TI - CYP1A1 gene polymorphism and risk of epithelial ovarian neoplasm.
SO - Gynecol Oncol 2002 Aug;86(2):124-8
AD - Department of Genetics, Hacettepe University Medical School, 06100, Sihhiye, Ankara, Turkey. email@example.com
OBJECTIVE: Gene-environment interactions have been the focus of a number of recent studies of the occurrence of human cancers, and an association between the risk and the CYP1A1*3 polymorphism has been noticed for several cancers. Previous studies suggest that estrogens are involved in the etiology of ovarian cancer. The cytochrome P450 1A1 (CYP1A1) gene polymorphism may play role in the development of epithelial ovarian neoplasm by detoxification of polycyclic hydrocarbons and other compounds and the concentration of estrogens and their metabolites. Therefore, we assessed the association of CYP1A1 gene polymorphism in patients with epithelial ovarian neoplasm in the Turkish populations through a case-control study. METHODS: Using an allele-specific polymerase chain reaction (PCR)-based method, CYP1A1*3 polymorphism, in exon 7 of the gene, was analyzed in 117 epithelial ovarian neoplasm patients and 202 control subjects. RESULTS: The CYP1A1 Ile/Val genotype significantly increased the risk for patients with epithelial ovarian neoplasm (OR 5.7, 95% CI 3.34-9.76). Furthermore, there were statistical differences in the distribution of CYP1A1 Val/Val genotype among all patients (OR 5.85, 95% CI 2.40-14.25). In other words, the presence of the Val allele significantly increased the risk of epithelial ovarian neoplasm. Among benign tumors, the frequency of Ile/Val and Val/Val genotypes was found to be statistically significant with an ORs of 6.01 and 4.38 (95% CI 2.61-13.84 and 1.04-18.38, respectively). In the benign serous ovarian tumors, patients with Ile/Val and Val/Val revealed a 7.2- and 10.5-fold higher risk of having ovarian carcinoma (95% CI 2.22-23.40 and 2.16-51.19), respectively. In the benign mucinous ovarian carcinoma patients, the frequency of Ile/Val was found to be statistically significant with an OR of 5.15 (95% CI 1.75-15.16). However, no patient with Val/Val genotype was observed in this group and no statistical distribution was performed. Among borderline tumors, CYP1A1 Ile/Val genotype significantly increased the risk for patients (OR 5.15, 95% CI 1.75-15.16). However, only one patient was observed with the Val/Val allele and the frequency of this genotype was not found to be statistically different with an OR of 2.50 (95% CI 0.27-22.64). Among ovarian cancer patients, there were statistically differences in the distribution of CYP1A1 Ile/Val and Val/Val genotypes (OR 5.73, 95% CI 3.04-10.76; and OR 7.42, 95% CI 2.80-19.66), suggesting that patients carrying these genotypes were at increased risk for ovarian carcinoma. In serous carcinoma, patients with CYP1A1 Ile/Val and Val/Val revealed a 6.5- and 10-fold higher risk of having ovarian cancer (OR 7.09, 95% CI 3.30-15.22; and OR 8.77, 95% CI 2.83-27.14). In mucinous carcinoma, patients with CYP1A1 Ile/Val and Val/Val also revealed a 5.4 and 10.5 times higher risk of having ovarian cancer. There were no statistical significance in the distribution of Val allele among endometroid-type cancer patients. CONCLUSIONS: Our data, although based on a small number of subjects, suggest that variant alleles of CYP1A1 gene in ovarian epithelial cells, directly or through other components, may contribute to initiation of ovarian carcinogenesis.
UI - 12144818
AU - Hefler LA; Ludwig E; Lampe D; Zeillinger R; Leodolter S; Gitsch G;
TI - Koelbl H; Tempfer CB Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer.
SO - Gynecol Oncol 2002 Aug;86(2):134-7
AD - Department of Obstetrics and Gynecology, University of Vienna Medical School, Vienna, Austria.
OBJECTIVE: The free radical nitric oxide is known to be critically involved in ovarian carcinogenesis by inducing apoptosis and by mediating various cytostatic and cytotoxic effects, but also by promoting growth, invasion, and metastasis. METHODS: We investigated two polymorphisms (exon 7 Glu298Asp and a 27-bp repeat in intron 4) of the gene encoding endothelial nitric oxide synthase (Nos3) in 130 patients with ovarian cancer, 26 patients with borderline ovarian cancer, and 133 healthy age-matched Caucasian women using PCR and pyrosequencing, respectively. RESULTS: Genotypes and allelic frequencies did not differ between patients with ovarian cancer and controls. Within the ovarian cancer group, however, the presence of at least one mutant allele of intron 4 was associated with advanced tumor stage and positive lymph node involvement, but not with tumor grading. The presence of the mutant allele of exon 7 was not associated with the investigated clinicopathological parameters. No correlation with patients' overall and disease-free survival was ascertained. CONCLUSIONS: We are the first to report on Nos3 polymorphisms in ovarian cancer. Allelic variation within intron 4 of Nos3 is associated with an advanced tumor stage and positive lymph node involvement in ovarian cancer.
UI - 12144824
AU - Kamazawa S; Kigawa J; Kanamori Y; Itamochi H; Sato S; Iba T; Terakawa N
TI - Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer.
SO - Gynecol Oncol 2002 Aug;86(2):171-6
AD - Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, 683-8504, Japan.
OBJECTIVE: The objective of this study was to determine the relationship between multidrug resistance and sensitivity to paclitaxel (PTX) in ovarian cancer. METHODS: We used human ovarian adenocarcinoma cell lines, KF, a PTX-resistant cell line (KFTx), SK-OV-3, and KOC7c. Additionally, 27 patients with ovarian cancer who had residual disease were examined. All patients underwent postoperative chemotherapy consisting of 175 mg/m(2) PTX and area under curve (AUC) 5 carboplatin. The sensitivity of the cells to PTX or cisplatin (CDDP) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. mRNA expression of multidrug resistance gene-1 (MDR-1) and multidrug resistance-associated protein-1 (MRP-1) and MRP-2 was determined by reverse transcription-polymerase chain reaction. beta-Tubulin polymerization and Bcl-2 phosphorylation were examined by Western blot analysis. RESULTS: Compared with KF, the IC(50) to PTX was 5.5-fold higher for KFTx, 0.3-fold for SK-OV-3, and 52.1-fold for KOC7c. The IC(50) to CDDP was 0.7-, 4.2-, and 5.8-fold, respectively. Expression of the MDR-1 gene was clearly observed in KFTx and KOC7c. Expression of MRP-1 was observed in SK-OV-3 and KOC7c. Expression of MRP-2 was detected only in KOC7c. CDDP enhanced beta-tubulin polymerization induced by PTX in CDDP-sensitive cells. Bcl-2 phosphorylation appeared after exposure to IC(50) PTX in all cells. Twenty-one patients responded to chemotherapy and six did not. Expression of the MDR-1 gene for nonresponders was significantly higher than that for responders (260.0 +/- 191.6 vs 9.3 +/- 21.8). With the cutoff value of MDR-1 expression at 100, the predictive value for chemoresponse was 96%. Expression of the MRP-1 and MRP-2 genes did not differ between nonresponders and responders. CONCLUSION: MDR-1 gene expression may be a useful predictor for PTX-based chemotherapy.
UI - 12144829
AU - Donovan KA; Greene PG; Shuster JL; Partridge EE; Tucker DC
TI - Treatment preferences in recurrent ovarian cancer.
SO - Gynecol Oncol 2002 Aug;86(2):200-11
AD - Department of Psychology, University of Alabama at Birmingham, 35294, USA.
OBJECTIVES: In the case of recurrent ovarian cancer, salvage therapy represents the potential to trade off between quality and quantity of life. Patient and physician face a choice between chemotherapy directed at slowing disease progression and supportive or palliative care that focuses on symptom management. To date, no studies have investigated the effects of best supportive care on ovarian cancer patients' quality of life and length of life as compared to salvage therapy. In other cancers, both quantity and quality of life considerations have been shown to affect treatment preferences. METHODS: Using a decision board, we assessed preferences for salvage therapy or palliative care in the case of recurrent ovarian cancer among 81 ovarian cancer patients receiving first-line chemotherapy and 75 Noncancer Controls. RESULTS: Compared to Noncancer Controls, ovarian cancer patients overwhelmingly preferred salvage therapy; quantity of life was of primary importance. In both groups, preference was not related to age, marital status, number of children, or employment status. On average, patients indicated they would switch from salvage therapy to palliative care when the median survival associated with salvage therapy was reduced to 5 months. Noncancer Controls would switch significantly sooner, when the median increment in survival period was reduced to 8 months. Switchpoint was not associated with life satisfaction, quality of life, or psychological or spiritual well-being in either group. CONCLUSIONS: The majority of women, independent of a cancer diagnosis, indicated a desire for continuing aggressive treatment, despite poor outcomes. Quality of life was of secondary importance, especially among ovarian cancer patients.
UI - 12144830
AU - Tiller K; Meiser B; Butow P; Clifton M; Thewes B; Friedlander M; Tucker
TI - K Psychological impact of prophylactic oophorectomy in women at increased risk of developing ovarian cancer: a prospective study.
SO - Gynecol Oncol 2002 Aug;86(2):212-9
AD - Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia. firstname.lastname@example.org
OBJECTIVES: The objectives of this study were twofold: to prospectively assess whether expressed intention to undergo prophylactic oophorectomy translated into uptake and to evaluate the psychological impact of the procedure in a sample of unaffected women with a strong family