National Cancer Institute®
Last Modified: June 1, 2002
UI - 12011131
AU - Grann VR; Jacobson JS; Thomason D; Hershman D; Heitjan DF; Neugut AI
TI - Effect of prevention strategies on survival and quality-adjusted survival of women with BRCA1/2 mutations: an updated decision analysis.
SO - J Clin Oncol 2002 May 15;20(10):2520-9
AD - Herbert Irving Comprehensive Cancer Center, Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 W 168th Street, New York, NY 10032, USA.
PURPOSE: This study updates findings regarding the effects of prophylactic surgery, chemoprevention, and surveillance on the survival and quality-adjusted survival of women who test positive for BRCA1/2 mutations. MATERIALS AND METHODS: Markov modeling of outcomes was performed in a simulated cohort of 30-year-old women who tested positive for BRCA1/2 mutations. The model incorporated breast and ovarian cancer incidence rates from the literature and mortality rates from the Surveillance, Epidemiology, and End Results Program. Quality adjustment of survival estimates were obtained from a survey of women aged 33 to 50 years. Sensitivity analyses were performed of varied assumptions regarding timing and effects of preventive measures on cancer incidence and adverse effects. RESULTS: A 30-year-old woman could prolong her survival beyond that associated with surveillance alone by use of preventive measures: 1.8 years with tamoxifen, 2.6 years with prophylactic oophorectomy, 4.6 years with both tamoxifen and prophylactic oophorectomy, 3.5 years with prophylactic mastectomy, and 4.9 years with both surgeries. She could prolong her quality-adjusted survival by 2.8 years with tamoxifen, 4.4 years with prophylactic oophorectomy, 6.3 years with tamoxifen and oophorectomy, and 2.6 years with mastectomy, or with both surgeries. The benefits of all of these strategies would decrease if they were initiated at later ages. CONCLUSION: Women who test positive for BRCA1/2 mutations may derive greater survival and quality adjusted survival benefits than previously reported from chemoprevention, prophylactic surgery, or a combination. Observational studies and clinical trials are needed to verify the results of this analysis of the long-term benefits of preventive strategies among BRCA1/2-positive women.
UI - 11987487
AU - Zakrzewska I
TI - [CA-125 antigen]
SO - Postepy Hig Med Dosw 2002;56(1):29-38
AD - Zaklad Laboratoryjnej Diagnostyki Klinicznej Akademii Medycznej w Bialymstoku.
This review describes the physicochemical and biological properties of antigen CA125 and clinical utility of antigen in oncologic diagnostic. CA125 is the most reliable marker for ovarian cancer in clinical practice. Analysis of CA125 values performed by many authors revealed its highest concentrations in serous and endrometrioid histological type. Serial measurements of CA125 are useful in monitoring the response to chemotherapy and follow-up the early detection of recurrent disease of patients with ovarian cancer.
UI - 11972384
AU - Reedy M; Gallion H; Fowler JM; Kryscio R; Smith SA
TI - Contribution of BRCA1 and BRCA2 to familial ovarian cancer: a gynecologic oncology group study.
SO - Gynecol Oncol 2002 May;85(2):255-9
AD - Division of Gynecologic Oncology, University of Kentucky, Lexington, KY 40536, USA.
OBJECTIVES: The aim of the study was to determine the prevalence of BRCA1 and BRCA2 germline mutations among ovarian cancer patients ascertained to have a family history of ovarian cancer. METHODS: Ovarian cancer patients were eligible if they had a family history of cancer that met any one of the following criteria: (1) a first-degree relative with ovarian cancer; (2) a second-degree relative with ovarian cancer plus a first-degree relative with breast cancer (diagnosed younger than 50 years of age); or (3) a first- and a second-degree relative with breast cancer (diagnosed younger than 50 years of age). The entire coding sequence of BRCA1 and exon 11 of BRCA2 were screened for germline alterations by single-strand conformation polymorphism analysis. RESULTS: Of 26 eligible patients screened for mutations, 12 had deleterious alterations, 8 in BRCA1 and 4 in BRCA2. A correlation was noted between the presence of a BRCA1 mutation and the strength of family history of breast ovarian cancer, with the likelihood of a mutation increasing with the number of affected relatives (P = 0.0002). No association was detected between the location of mutations in BRCA1 and the ratio of ovarian cancer cases relative to breast cancer (P = 0.28). CONCLUSIONS: Mutations in BRCA1 or BRCA2 are present in about 50% of ovarian cancer patients with at least one first-degree relative with disease, and in 70% of patients with two or more relatives with ovarian cancer. (c) 2002 Elsevier Science (USA).
UI - 11972385
AU - Kim JS; Lee SH; Cho YS; Choi JJ; Kim YH; Lee JH
TI - Enhancement of the adenoviral sensitivity of human ovarian cancer cells by transient expression of coxsackievirus and adenovirus receptor (CAR).
SO - Gynecol Oncol 2002 May;85(2):260-5
AD - Clinical Research Center, Samsung Biomedical Research Institute, Seoul 135-710, Korea.
OBJECTIVE: The coxsackievirus and adenovirus receptor (CAR) is known to be a primary receptor for attachment during adenovirus infection of target cells and thus is closely related to adenoviral infection efficiency. To extend this notion to human ovarian cancer, we investigated the difference in expression levels of CAR in human ovarian cancer cell lines and whether their adenoviral sensitivities are enhanced by transient transfection of the CAR gene. METHODS: Adenoviral infection efficiency was examined by flow cytometry analysis, beta-galactosidase staining, and beta-galactosidase activity assay. Expression of the CAR-specific mRNA and protein was analyzed by reverse transcription polymerase chain reaction and flow cytometry, respectively. RESULTS: Expression of CAR in human ovarian cancer cell lines (SKOV3, 2774, PA-1, and OVCAR3) appeared to be correlated with their susceptibilities to adenovirus-mediated gene delivery. The 2774 and PA-1 cells expressing an easily detectable level of CAR on the cell surface showed a higher susceptibility to infection with both AdCMVGFP and AdRSVbetagal than SKOV3 and OVCAR3 cells, both of which had hardly detectable levels of CAR. Ectopic expression of the CAR gene by transient transfection of these ovarian cancer cells resulted in a dramatic increase in their adenoviral sensitivities. CONCLUSION: These data show that the expression of CAR is closely related to susceptibility to adenovirus infection in human ovarian cancer cells. These results indicate that the CAR gene can be a useful tool in boosting the efficiency of adenoviral vector-mediated gene therapy against human ovarian cancer. (c) 2002 Elsevier Science (USA).
UI - 11972399
AU - Le T; Adolph A; Krepart GV; Lotocki R; Heywood MS
TI - The benefits of comprehensive surgical staging in the management of early-stage epithelial ovarian carcinoma.
SO - Gynecol Oncol 2002 May;85(2):351-5
AD - Division of Gynecologic Oncology, Dept. of Obstetrics, Gynecology, and Reproductive Sciences, University of Saskatchewan, Royal University Hospital, 103 Hospital Drive, Saskatoon, Saskatchewan, Canada S7N 0W8. firstname.lastname@example.org
OBJECTIVE: The management of understaged patients with apparent clinically early ovarian cancer is difficult. Options include offering chemotherapy based on histopathologic factors or reoperation to obtain the necessary information needed to assign an accurate surgical stage. This study aims to compare these two approaches and to define the role of staging surgery in this common patient population. METHODS: Retrospective chart reviews were carried out at the Universities of Manitoba and Saskatchewan over the period 1975 to 1999. Demographic data and surgical findings were abstracted and entered into a computerized database for analysis. Patients not having surgical staging procedures were offered platinum-based chemotherapy based on high tumor grades, dense adhesions, and presence of surface excrescences or large necrotic areas. Patients with surgically proven stage I disease were treated with no further therapy regardless of histopathologic factors. Descriptive statistics are used to summarize the data. Logistic and Cox regression models are used to identify significant predicting factors for recurrences and progression-free intervals. RESULTS: One hundred and thirty-eight patients presented with tumor macroscopically confined to the ovary at the time of laparotomy. The median age at presentation is 56.5 (18-90). The histology distribution was serous tumor in 28.3%, mucinous in 26.1%, endometrioid in 23.2%, clear cell in 14.5%, anaplastic in 2.2%, and mixed types in 5.8%. The grade distribution was 47.1% grade 1, 27.5% Grade 2, and 25.4% Grade 3. Sixty-eight percent of the patients had a comprehensive surgical staging procedure initially. Thirty-six percent of these patients were found to have extraovarian metastases and were subsequently treated with adjuvant chemotherapy. Forty-three percent of those not having staging laparotomy were offered chemotherapy based on high risk factors only. At a median follow-up of 58 months. 77% of patients remained disease-free and 23% had recurrent disease. Of 60 patients with surgically proven stage I treated expectantly, 6 (10%) recurred, whereas of 25 unstaged patients treated expectantly due to lack of risk factors 7 (28%) recurred (P = 0.036). In patients treated expectantly, a significant survival advantage was noted in the staged group. Logistic regression showed age (OR 1.032, P = 0.043), high grade (OR 4.16, P = 0.003), and lack of a proper staging surgery (OR 2.62, P = 0.032) to be important factors predicting recurrence. In terms of progression-free interval, only age (OR 1.027, P = 0.048) and tumor grade (OR 3.62, P = 0.05) are significant predictors. CONCLUSION: Absence of surgical pathologic high-risk factors is inferior to comprehensive staging laparotomy findings in guiding recommendations for subsequent adjuvant therapy. Patients who have not been properly staged stand a significant risk of recurrent disease despite more frequent use of chemotherapy. All clinically early-stage ovarian cancer patients should be considered for comprehensive staging surgery prior to further treatment recommendations. (c) 2002 Elsevier Science (USA).
UI - 11972407
AU - Neven P; Goldstein SR; Ciaccia AV; Zhou L; Silfen SL; Muram D
TI - The effect of raloxifene on the incidence of ovarian cancer in postmenopausal women.
SO - Gynecol Oncol 2002 May;85(2):388-90
AD - Department of Obstetrics and Gynecology, Algemene Kliniek St.-Jan, Broekstraat 114, B-1000 Brussels, Belgium. Patrick.email@example.com
OBJECTIVE: The aim of this study was to determine the incidence of ovarian cancer in postmenopausal women treated with raloxifene compared with placebo. METHODS: This analysis comprises integrated data from seven randomized, placebo-controlled trials of raloxifene (N = 9837). Ovarian cancer cases were identified from the safety database and reviewed by a gynecologic adjudication review board. RESULTS: Sixteen cases of ovarian cancer were reported: 8 women (79.4/100,000 patient-years) on placebo and 8 (37.4/100,000 patient-years) on pooled raloxifene doses. The relative risk of ovarian cancer associated with raloxifene therapy was 0.50 (95% confidence interval, 0.19-1.35). CONCLUSION: Raloxifene use was not associated with an increased risk for ovarian cancer. (c) 2002 Elsevier Science (USA).
UI - 11972408
AU - Markman M
TI - The use of PET scanning in ovarian cancer.
SO - Gynecol Oncol 2002 May;85(2):391; discussion 391-2
UI - 11987569
AU - Sevcik L; Klat J; Koliba P
TI - [Hormone replacement therapy and ovarian tumors]
SO - Ceska Gynekol 2002 Mar;67(2):55-8
AD - Porodnicko-gynekologicka klinika, FNsP Ostrava.
OBJECTIVE: Analysis of risk and protective factors and hormone replacement therapy in the aethiology and pathogenesis of ovarian cancer. The role of hormone replacement therapy in the complex treatment in women with ovarian cancer is discussed. DESIGN: Reviewed article. SETTING: Department of Obstetrics and Gynaecology, University Hospital Ostrava. METHODS: Analysis of epidemiological studies. CONCLUSION: The role of hormone replacement therapy as a risk factor of ovarian cancer has not been confirmed. Hormone replacement therapy as a part of supportive and symptomatic therapy has been acceptable in a great deal of patients with ovarian cancer.
UI - 12015763
AU - Yang DH; Smith ER; Cohen C; Wu H; Patriotis C; Godwin AK; Hamilton TC;
TI - Xu XX Molecular events associated with dysplastic morphologic transformation and initiation of ovarian tumorigenicity.
SO - Cancer 2002 May 1;94(9):2380-92
AD - Ovarian Cancer Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
BACKGROUND: Disabled-2 (Dab2), a candidate tumor suppressor of ovarian carcinoma, frequently (around 80%) loses its expression in ovarian tumors. Expression of exogenous Dab2 in tumor cell lines negatively regulates growth and suppresses the downstream signal of the Ras/mitogen activated protein kinase mitogenic pathway. The inactivation of Dab2 is believed to be an early event in ovarian tumorigenicity. METHODS: The authors analyzed the correlation among expression of Dab2, presence of basement membrane (collagen IV and laminin), morphologic alteration of the surface epithelial cells, and expression of the mitotic index marker Mib-1 in 50 archived ovarian tumors by an immunohistochemical approach. The stainings of Dab2, Mib-1, collagen IV, and laminin in premalignant lesions bordering both normal and neoplastic ovarian surface epithelium from adjacent slides were analyzed in 50 ovarian tumors. RESULTS: In these 50 ovarian tumors, the percentage of Mib-1 positive tumor cells distributed in a wide range, from 1% to 75%, and there has no strong correlation with the expression of Dab2. However, in the premalignant regions bordering tumor and normal ovarian surface epithelium, the loss of Dab2 expression closely correlated with the dysplastic morphologic transition and Mib-1 expression of the ovarian surface epithelial cells. In 20 foci in 12 out of the 50 tumors, a transition from normal to neoplastic morphology within a contiguous epithelium was observed, and in all cases the morphologic change correlated with the loss of Dab2 staining. In addition, the collagen and laminin staining of the basement membrane were absent or weakened in pre-malignant epithelium prior to loss of Dab2 expression in all these 20 cases. Nevertheless, collagen IV and laminin were detectable in established adenomas on the same tumor slides. CONCLUSIONS: The loss of Dab2 is closely associated with the transition of ovarian surface epithelial cells to premalignant states and is likely involved in the initiation of ovarian tumorigenicity. Transient loss of collagen IV and laminin in the basement membrane of the premalignant epithelium and subsequent inactivation of Dab2 are common early events associated with tumorigenicity of the ovarian surface epithelium. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10497
UI - 12015770
AU - Chiriva-Internati M; Wang Z; Salati E; Timmins P; Lim SH
TI - Tumor vaccine for ovarian carcinoma targeting sperm protein 17.
SO - Cancer 2002 May 1;94(9):2447-53
AD - Division of Hematology and Oncology, Texas Tech University School of Medicine at Amarillo, USA.
BACKGROUND: The authors previously identified sperm protein 17 (Sp17) as being expressed in patients with multiple myeloma. The restricted expression of Sp17 in normal tissue makes it an ideal target for tumor vaccine. In the current study, the authors extended their research to include ovarian carcinoma. METHODS: A pair of sequence specific primers was used in reverse transcriptase-polymerase chain reaction to determine the gene expression of Sp17. A recombinant Sp17 protein was used with monocyte-derived dendritic cells and autologous peripheral blood mononuclear cells to generate Sp17 specific cytotoxic T-lymphocytes (CTLs). The successful generation of Sp17 specific CTLs was confirmed using standard (51)chromium-release assays. RESULTS: Sp17 was found to be expressed in the primary tumor cells from 70% of the patients with ovarian carcinoma. Human leukocyte antigen (HLA) class I- restricted Sp17 specific CTLs were generated successfully from the peripheral blood of three patients with ovarian carcinoma at the time of disease presentation. These CTLs were able to lyse autologous Epstein-Barr virus-transformed lymphoblastoid cells in a Sp17-dependent manner. Target lysis was HLA class I-dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecules. The CTLs also lysed Sp17-positive autologous tumor cells, suggesting that Sp17 is processed and presented in association with the HLA class I molecules in Sp17- positive tumor cells in a concentration and configuration that could be recognized by recombinant protein-primed CTLs. Tumor cell killing by the CTLs appeared to be mediated through the perforin pathway. Flow cytometric analysis of the CTLs indicated that they predominantly were CD8 in phenotype and produced interferon-gamma and scant amounts of interleukin-4. CONCLUSIONS: The results of the current study suggest the potential of Sp17 as a target for immunotherapy in patients with ovarian carcinoma. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10506
UI - 11997559
AU - Coakley FV; Choi PH; Gougoutas CA; Pothuri B; Venkatraman E; Chi D;
TI - Bergman A; Hricak H Peritoneal metastases: detection with spiral CT in patients with ovarian cancer.
SO - Radiology 2002 May;223(2):495-9
AD - Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. firstname.lastname@example.org
PURPOSE: To determine the accuracy of spiral computed tomography (CT) in the depiction of peritoneal metastases by using surgical findings in patients with ovarian cancer as the standard of reference. MATERIALS AND METHODS: Three independent readers reviewed the preoperative CT scans obtained in 64 patients who underwent primary surgery for ovarian cancer. Readers rated the likelihood of peritoneal metastases on a five-point scale and recorded the presence or absence of ascites, parietal peritoneal thickening or enhancement, and small-bowel wall thickening or distortion. Peritoneal metastases were identified as nodular, plaquelike, or infiltrative soft-tissue lesions in the peritoneal fat or on the peritoneal surface. Area under the receiver operating characteristic curve was calculated for each reader. Interreader agreement was evaluated with the kappa statistic. Descriptive statistical data were determined with dichotomized ratings (1-3 = absent; 4-5 = present). RESULTS: Areas under the receiver operating characteristic curves for the three readers were 0.95, 0.93, and 0.89. Paired kappa values ranged from 0.75 to 0.91. Reader sensitivity for metastases 1 cm or smaller in maximum diameter (25%-50%) was significantly (P <.05) lower than overall sensitivity (85%-93%). Ascites, parietal peritoneal thickening or enhancement, and small-bowel wall thickening or distortion demonstrated positive predictive values of 72%-93%, with kappa values of 0.12-0.80. CONCLUSION: Spiral CT is accurate in the depiction of peritoneal metastases from ovarian cancer, although sensitivity is reduced in patients with tumor implants 1 cm or smaller. Ancillary signs of peritoneal malignancy are limited by low interobserver agreement. Copyright RSNA, 2002
UI - 11882011
AU - Liu Y; Ganesan TS
TI - Tumour suppressor genes in sporadic epithelial ovarian cancer.
SO - Reproduction 2002 Mar;123(3):341-53
AD - ICRF Molecular Oncology Laboratories, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
Ovarian cancer is the most frequent cause of death from gynaecological malignancies in the western world, and sporadic epithelial ovarian cancer is its most predominant form. The aetiology of sporadic ovarian cancer remains unknown. Genetic studies have enabled a better understanding of the evolution of tumour progression. A major focus of research has been to identify tumour suppressor genes implicated in sporadic ovarian cancer over the past decade. Several tumour suppressor genes have been identified by strategies such as positional cloning and differential expression display. Further research is warranted to understand fully their contribution to the pathogenesis of sporadic ovarian cancer.
UI - 11992549
AU - Kudoh K; Ichikawa Y; Yoshida S; Hirai M; Kikuchi Y; Nagata I; Miwa M;
TI - Uchida K Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer.
SO - Int J Cancer 2002 Jun 1;99(4):579-82
AD - Department of Obstetrics and Gynecology, Self Defense Force Sendai Hospital, Miyagi 983-8580, Japan. email@example.com
To define the involvement of p16/CDKN2 and p15/MTS2 tumor-suppressor genes for response to chemotherapy in primary epithelial ovarian cancer, we analyzed alterations of the gene in 45 patients who were treated with primary cytoreductive surgery followed by 6 courses of cis-diamminedichloroplatinum (II) (cisplatin)-based combination chemotherapy. Homozygous deletion of p16/CDKN2 and p15/MTS2 genes was found in 8 (18%) and 15 (33%) cases, respectively. Response to the chemotherapy was confirmed by finding at second surgery after the chemotherapy in 26 patients, resulting in 17 responders and 9 nonresponders. The abundance of gene deletion in nonresponders (56%) was significantly higher (p = 0.0463) when compared to that in responders (18%). Moreover, the deletion of genes was a significant poor prognostic factor (p = 0.0441) in advanced ovarian cancer. These results suggest that deletion of p16/CDKN2 and/or p15/MTS2 is a potential indicator for poor chemotherapy response and adverse prognosis in ovarian cancer patients. Copyright 2002 Wiley-Liss, Inc.
UI - 11992553
AU - Lukanova A; Toniolo P; Lundin E; Micheli A; Akhmedkhanov A; Muti P;
TI - Zeleniuch-Jacquotte A; Biessy C; Lenner P; Krogh V; Berrino F; Hallmans G; Riboli E; Kaaks R Body mass index in relation to ovarian cancer: a multi-centre nested case-control study.
SO - Int J Cancer 2002 Jun 1;99(4):603-8
AD - Department of Nutrition and Cancer, International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France. firstname.lastname@example.org
The incidence of ovarian cancer is up to 10 times higher in Western countries than in rural Asia and Africa. One common consequence of a Western lifestyle is the development of excessive body weight and obesity. A multi-centre prospective study was conducted to investigate the association between body mass index (BMI) and ovarian cancer risk. A case-control study was nested within 3 prospective cohorts in New York (USA), Umea (Sweden) and Milan (Italy). Information on anthropometry, demographic characteristics, medical history and lifestyle was obtained at the time of subjects' recruitment in each cohort. Women diagnosed with primary, invasive epithelial ovarian cancer from the 3 cohorts (n = 122) diagnosed 12 months or later after recruitment into the respective cohort served as case subjects. For each case subject, 2 control subjects that matched the case subject on cohort, menopausal status, age and date of recruitment were randomly identified. Data were analyzed by conditional logistic regression. There was an inverse association between BMI and ovarian cancer risk. For increasing quartiles of BMI above the lowest, the ORs were 0.62 (0.32-1.21), 0.59 (0.30-1.17) and 0.46 (0.23-0.92), p = 0.03. Analyses limited to women diagnosed 3 or more years after recruitment into the cohorts did not alter these findings. When obese women (BMI > 30) were compared to lean women (BMI < or = 23), the inverse association became stronger, with an OR of 0.38 (0.17-0.85), p < 0.02. There was some evidence of direct association of ovarian cancer with height, which was limited to cancers diagnosed before age 55. Our data suggest that increasing body weight may confer a protection against ovarian cancer. Copyright 2002 Wiley-Liss, Inc.
UI - 11977327
AU - Krupski W; Jakiel G; Zlomaniec J
TI - Diagnostic value of US and CT in the assessment of ovarian teratomas and their qualifications for surgical treatment with laparoscopic method.
SO - Ann Univ Mariae Curie Sklodowska [Med] 2001;56():285-93
AD - 2nd Department of Radiology, Medical University of Lublin.
In the group of 17 women after surgery with histopathologically confirmed diagnosis of teratomas diagnostic usefulness of US and CT was analysed. Differentiated echostructure of tumours was correlated with different densities of pathologic tissues in CT examination, also after their contrast enhancement. In 2 patients teratomas of both ovaries were recognised, in the remaining 15 women tumours were unilateral. In total morphologic pictures of 19 teratomas were assessed, 9 times tumours with prevailing liquid component had the picture of a thick-walled cyst, 7 times these were hyperechogenic fatty foci and in 3 cases had the character of solid tumours. Teratomas had different morphologic pictures, but it was possible to show the prevalence of one element and classify the tumour to one of the three types of teratomas. It was found that US examination, due to its high frequency, lets early diagnose teratomas before they are accessible in the clinical exam, in the symptomless period or when they give indirect symptoms, usually dysuric ones. CT examination, due to its high sensitivity in recognising fatty tissue and calcifications, is necessary before laparoscopic operation requiring fragmentation of big tumours to determine their character.
UI - 11992414
AU - Bertone ER; Newcomb PA; Willett WC; Stampfer MJ; Egan KM
TI - Recreational physical activity and ovarian cancer in a population-based case-control study.
SO - Int J Cancer 2002 May 20;99(3):431-6
AD - Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003-9304, USA. email@example.com
Results from epidemiologic studies of physical activity and ovarian cancer have been inconsistent, with 2 prospective studies reporting a modest positive association. We evaluated this relationship in a population-based case-control study conducted in Massachusetts and Wisconsin. Incident cases diagnosed between 1991 and 1994 were identified through statewide tumor registries. Community controls were selected randomly from lists of licensed drivers and Medicare recipients. Participation in moderate and vigorous recreational physical activity at age 12, age 20 and 5 years prior to diagnosis was assessed by telephone interview. Data were available for 327 cases and 3,129 controls. Results were adjusted for age, parity and other ovarian cancer risk factors. Total and vigorous physical activity were not associated with a substantial decrease in ovarian cancer risk at any age. The relative risk (RR) for women reporting > or = 7 vs. 0 hr/week of recent vigorous activity was 0.85 [95% confidence interval (CI) = 0.39-1.86; p for trend = 0.31]. When metabolic equivalent task (MET) hours of activity were estimated, only women in the highest category had any reduction in risk (RR for > 42 MET-hours/week at the reference age = 0.70; 95% CI = 0.36-1.35; p for trend = 0.41). Overall, our results provide only limited support for an inverse association between recreational physical activity and risk of ovarian cancer. Copyright 2002 Wiley-Liss, Inc.
UI - 12039933
AU - Berry DA; Iversen ES Jr; Gudbjartsson DF; Hiller EH; Garber JE; Peshkin
TI - BN; Lerman C; Watson P; Lynch HT; Hilsenbeck SG; Rubinstein WS; Hughes KS; Parmigiani G BRCAPRO validation, sensitivity of genetic testing of BRCA1/BRCA2, and prevalence of other breast cancer susceptibility genes.
SO - J Clin Oncol 2002 Jun 1;20(11):2701-12
AD - Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. firstname.lastname@example.org
PURPOSE: To compare genetic test results for deleterious mutations of BRCA1 and BRCA2 with estimated probabilities of carrying such mutations; to assess sensitivity of genetic testing; and to assess the relevance of other susceptibility genes in familial breast and ovarian cancer. PATIENTS AND METHODS: Data analyzed were from six high-risk genetic counseling clinics and concern individuals from families for which at least one member was tested for mutations at BRCA1 and BRCA2. Predictions of genetic predisposition to breast and ovarian cancer for 301 individuals were made using BRCAPRO, a statistical model and software using Mendelian genetics and Bayesian updating. Model predictions were compared with the results of genetic testing. RESULTS: Among the test individuals, 126 were Ashkenazi Jewish, three were male subjects, 243 had breast cancer, 49 had ovarian cancer, 34 were unaffected, and 139 tested positive for BRCA1 mutations and 29 for BRCA2 mutations. BRCAPRO performed well: for the 150 probands with the smallest BRCAPRO carrier probabilities (average, 29.0%), the proportion testing positive was 32.7%; for the 151 probands with the largest carrier probabilities (average, 95.2%), 78.8% tested positive. Genetic testing sensitivity was estimated to be at least 85%, with false-negatives including mutations of susceptibility genes heretofore unknown. CONCLUSION: BRCAPRO is an accurate counseling tool for determining the probability of carrying mutations of BRCA1 and BRCA2. Genetic testing for BRCA1 and BRCA2 is highly sensitive, missing an estimated 15% of mutations. In the populations studied, breast cancer susceptibility genes other than BRCA1 and BRCA2 either do not exist, are rare, or are associated with low disease penetrance.
UI - 12052591
AU - Tay EH; Grant PT; Gebski V; Hacker NF
TI - Secondary cytoreductive surgery for recurrent epithelial ovarian cancer.
SO - Obstet Gynecol 2002 Jun;99(6):1008-13
AD - Gynaecological Cancer Centre, Royal Hospital for Women, Department of Obstetrics and Gynaecology, University of New South Wales, Sydney, Australia.
OBJECTIVE: To review our experience with secondary cytoreductive surgery for recurrent epithelial ovarian cancer with regard to its feasibility, morbidity, mortality, patient selection, and survival. METHODS: Forty-six patients who underwent secondary cytoreductive surgery at the were retrospectively reviewed. The mean age at surgery was 50.3 years, and the median disease-free interval was 26 months. Eighty-nine percent of patients had a disease-free interval of at least 12 months. Twenty-five patients (54%) had localized disease at the time of surgery. Univariate survival outcomes were analyzed using the log rank test, and survival curves were calculated using the method of Kaplan-Meier. RESULTS: Two patients (4%) were inoperable and 19 patients (41%) were cytoreduced to no macroscopic disease. There was one postoperative death (2%), and four patients (8.7%) had significant postoperative morbidity. With a median follow-up of 88 months, the overall median survival was 22.5 months. Patients with a disease-free interval of less than 12 months after their initial treatment had a median survival of 6 months, compared with 11 months if the disease-free interval was 12-24 months and 39 months for those with a disease-free interval of 24 months or more (P =.001, log rank). Patients who had any residual disease had a median survival of 11 months, whereas those with no residual disease had a median survival of 38 months (P =.002, log rank). CONCLUSION: For carefully selected patients with recurrent epithelial ovarian cancer: 1) complete surgical resection is feasible more commonly than with primary cytoreduction, 2) serious morbidity and mortality are acceptable, and 3) significant survival benefit accrues when a) all macroscopic disease can be resected, or b) the disease-free interval is 24 months or more.
UI - 11911974
AU - Matsumoto K; Yoshikawa H; Yasugi T; Onda T; Nakagawa S; Yamada M; Kawana
TI - K; Minaguchi T; Oda K; Hasumi Y; Taketani Y Distinct lymphatic spread of endometrial carcinoma in comparison with cervical and ovarian carcinomas.
SO - Cancer Lett 2002 Jun 6;180(1):83-9
AD - Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan.
The distribution of metastatic pelvic lymph nodes (PLNs) and aortic lymph nodes (ALNs) in 27 node-positive endometrial carcinomas (ECs) was analyzed in comparison with that in 25 node-positive cervical carcinomas (CCs) and 58 node-positive ovarian carcinomas (OCs). All patients underwent systematic pelvic and aortic lymphadenectomy. Lymph nodes were classified into the five subgroups: ALN above the inferior mesenteric artery (IMA; A1), ALN below the IMA (A2), the common iliac and sacral LNs (P1), the internal and external iliac LNs and obturator LNs (P2) and the suprainguinal LNs (P3). EC was similar to CC in that metastases to P2 were more frequent compared to A1 or A2, whereas EC and OC shared a common feature in that A1, A2 and P2 were involved at high rates. ALN metastases were significantly associated with P1 positivity in both EC and CC (P<0.05), but not in OC. However, the incidence of both ALN and PLN metastases in EC (67%) was similar to that in OC (61%), being much higher than that in CC (36%). ALN involvement alone was observed in 7% for EC, 0% for CC and 21% for OC. Based on the distribution of LN metastases, it appears that CC metastasizes primarily to PLN, whereas OC metastasizes almost equally to both PLN and ALN. Interestingly, EC can directly metastasize to both PLN and ALN with PLN metastases being dominant, a distinct lymphatic spread pattern better viewed as being somewhere between CC and OC.
UI - 11950960
AU - Gallagher NJ; Eliopoulos AG; Agathangelo A; Oates J; Crocker J; Young LS
TI - CD40 activation in epithelial ovarian carcinoma cells modulates growth, apoptosis, and cytokine secretion.
SO - Mol Pathol 2002 Apr;55(2):110-20
AD - CRC Institute for Cancer Studies, University of Birmingham Medical School, Birmingham B15 2TA, UK.
BACKGROUND/AIMS: CD40, a member of the tumour necrosis factor (TNF) receptor family, is expressed on a variety of haematopoietic cells and is crucial in orchestrating both humoral and cellular immune responses. CD40 is also expressed on some carcinoma cells, where its function remains largely unknown. This study investigated the effects of CD40 ligation on ovarian carcinoma cell growth and apoptosis and on cytokine production, in addition to the role of the NF-kappa B and JNK signalling pathways. METHODS: CD40 expression was measured in epithelial ovarian carcinoma (EOC) biopsies by immunohistochemistry and in EOC cell lines by flow cytometry. To examine the effects of CD40 ligation on cell growth recombinant soluble CD40 ligand was used to stimulate EOC cell lines and growth was measured by MMT assays. Cytokine production was measured by enzyme linked immunosorbent assays interleukin 8 (IL-8) gene transcription was estimated by means of reverse transcription polymerase chain reaction. The integrity of the CD40 signalling pathway in those cell lines that did not produce cytokines in response to CD40 ligation was assessed by the detection of the transcription factor NF-kappa B by an electrophoretic mobility shift assay. To investigate the defect in the NF-kappa B pathway the phosphorylation status of I kappa B alpha was determined by an antibody specific to phosphorylated I kappa B alpha and dissociation of the I kappa B alpha-p65 complex was assessed by co-immunoprecipitation. RESULTS: CD40 is expressed in primary ovarian carcinoma biopsies and EOC cell lines. CD40 ligation resulted in growth inhibition in most of these carcinoma cell lines and was also found to promote apoptosis, with this last effect only being evident in early passage EOC cells. CD40 ligation also induced significant IL-6 and IL-8 production in most of the EOC cell lines examined and it was confirmed for IL-8 that this effect was regulated at the transcriptional level. NF-kappa B activation in response to CD40 ligation was found in three of the EOC cell lines and specific defects in the CD40 induced NF-kappa B pathway were identified in two cell lines. However, CD40 engagement induced JNK activation in all the EOC cell lines. CONCLUSIONS: These data suggest that the CD40 pathway is functional in ovarian carcinoma cells and highlight the need for further studies to provide insight into the role of CD40 in the carcinogenic process and the possible exploitation of this pathway for novel therapeutic approaches.
UI - 11975680
AU - Zhang GL; Xu KL
TI - Loss of heterozygosity at chromosome 3p in epithelial ovarian cancer in China.
SO - Int J Gynecol Cancer 2002 Mar-Apr;12(2):198-201
AD - Department of Gynecological Oncology, Shanghai Cancer Hospital, Fu Da University, Shanghai, China.
The aim of this investigation was to determine the relationship between 3p loss of heterozygosity (LOH) and the pathogenesis of ovarian cancer. Fifty cases of epithelial ovarian tumor, including 40 cases with malignant tumors and 10 cases with benign tumors, were examined by polymerase chain reaction (PCR) with D3s1228 and D3s1038 microsatellite polymorphism markers at 3p. Thirty-two of the 40 cases (80%) with ovarian cancer showed LOH at 3p14 or 3p25, but only 1 of 10 cases (10.0%) with benign ovarian tumor showed 3p LOH. Among them, 24 cases (60.0%) had LOH at 3p14 and 16 cases (40.0%) at 3p25, as well as 8 cases (20.0%) with codeletion on both 3p14 and 3p25. According to FIGO staging, the frequency of LOH at 3p in ovarian cancer patients with stage IIIa or IIIb was higher than that in patients with stage I or II (P < 0.05), but there was no relationship between 3p LOH and the pathologic types in epithelial ovarian cancer (P > 0.05). Since 3p LOH commonly occurs in epithelial ovarian cancer and LOH at 3p14 and 3p25 correlates to the staging of ovarian cancer, it is suggested that there are some candidate ovarian TSGs harbored in the 3p region and that the detection of 3p LOHs may be used as a genetic marker for monitoring the development of ovarian cancer.
UI - 12000179
AU - Garner CM; Hubbold LM; Chakraborti PR
TI - In vitro testing of platinum-based drugs on a panel of human ovarian tumour cell lines.
SO - Br J Biomed Sci 2002;59(1):15-9
AD - Oncology Research Laboratory, Derby Cancer Centre, Derby City General Hospital. email@example.com
Much improvement in the treatment of ovarian cancer has been achieved since the introduction of platinum compounds in the 1980s, with the result that single-agent platinum-based therapy following primary surgery is now the standard treatment for advanced ovarian cancer. The main therapeutic effect of chemotherapy is based on the sensitivity of the patient's tumour to the drug. However, testing a new chemical compound on humans requires much care, time and resources, whereas prior testing of drugs on cancer cell lines may indicate those drugs particularly suited to treatment of a specific disease. This study investigates the actions of two established platinum-based chemotherapeutic agents (cisplatin and carboplatin) on a panel of 10 human ovarian cancer cell lines. Each cell line was plated onto 96-well tissue culture plates, incubated for 72 hours with the drug, formalin-fixed and then assessed using the methylene blue colorimetric microassay to detect viable cells. The IC50 values for each cell line were calculated in order to assess the toxicity of each drug, and a wide range of responses were observed across the 10 cell lines investigated. This suggests that the panel reflected the heterogeneous nature of ovarian cancer, a malignancy in which a huge range of drug sensitivities can be seen even among tumours of the same histological type. The results indicate that the panel could be of use either as a primary screen to test new drugs against ovarian cancer or to investigate the drug resistance that is so common in this disease.
UI - 10758808
AU - Sari R; Buyukberber S; Sevinc A; Ates M; Balat O; Hascalik S; Turk M
TI - The effects of abdominal and bimanual pelvic examination and transvaginal ultrasonography on serum CA-125 levels.
SO - Clin Exp Obstet Gynecol 2000;27(1):69-71
AD - Inonu University, School of Medicine, Department of Internal Medicine, Turgut Ozal Medical Center, Malatya, Turkey.
The need for the early detection of ovarian cancer continues to be one of the most important issues in women's health care. The three most extensively evaluated screening methods for ovarian cancer are pelvic examination, transvaginal ultrasonography, and serum CA-125 levels. The answers to questions such as should the levels of CA-125 be measured before bimanual pelvic examination or transvaginal ultrasonography or do abdominal examinations effect the levels of CA-125 are obscure. Fifty-four otherwise healthy female volunteers at the preovulatory phase of the menstrual cycle complaining of vaginal candidiasis were divided into 3 groups. Abdominal (group 1), bimanual pelvic (group 2), and transvaginal ultrasonography (group 3) examination was performed and serum CA-125 levels were evaluated prior to examination and 10 minutes, 6 hours, and 24 hours after the examination. As a result, serum CA-125 levels (U/ml) were found to be 8.13 +/- 4.76, 8.23 +/- 5.05, 8.32 +/- 4.88, and 8.33 +/- 4.94 in the group of abdominal examination, respectively, 8.23 +/- 4.89, 8.45 +/- 5.15, 8.77 +/- 4.96, and 8.79 +/- 5.50 in the group of bimanual pelvic examination, respectively, and 8.19 +/- 4.56, 8.30 +/- 5.10, 8.81 +/- 5.56, and 8.88 +/- 5.71 in the group of transvaginal ultrasonography, respectively. The serum CA-125 levels detected prior to examinations were statistically insignificant when compared with the results obtained at 10 minutes, 6 hours, and 24 hours later in all three groups. We concluded that physical examination, either abdominal or pelvic, and transvaginal ultrasonography do not change the serum levels of CA-125.
UI - 12014634
AU - Jin X; Burke W; Rothman K; Lin J
TI - Resistance to p53-mediated growth suppression in human ovarian cancer cells retain endogenous wild-type p53.
SO - Anticancer Res 2002 Mar-Apr;22(2A):659-64
AD - Department of Obstetrics and Gynecology, University of Michigan Comprehensive Cancer Center, Ann Arbor 48109-0936, USA.
Cancer cells containing mutated p53 are sensitive to the re-introduction of the wild-type (wt) p53. We sought to determine whether ovarian cancer cells that retain wt p53 are sensitive to the re-introduction of wt p53. Our results demonstrated that A2780 and PA-1 cells, which retain wt p53, are more resistant to apoptosis and growth suppression induced by exogenous expression of wt p53 than SKOV-3 and Caov-3 cells that contain mutated p53. All cell lines, except PA-1, showed induction of the p53-targeted genes. Further, inhibitors of p53-dependent apoptosis, mdm2 and Bcl-xL were not overexpressed in A2780 and PA-1 cells. These results suggest that one major defect in PA-1 cells is due to abrogation of induction of the p53-targets which is independent of mdm2 and Bcl-xL. Although A2780 cells showed induction of the p53-targeted genes, the cleavage of caspase-9 was undetectable. Therefore, p53-dependent apoptosis may be blocked upstream or at the caspase-9 level in A2780 cells.
UI - 12014680
AU - Arzimanoglou II; Hansen LL; Chong D; Li Z; Psaroudi MC; Dimitrakakis C;
TI - Jacovina AT; Shevchuk M; Reid L; Hajjar KA; Vassilaros S; Michalas S; Gilbert F; Chervenak FA; Barber HR Frequent LOH at hMLH1, a highly variable SNP in hMSH3, and negligible coding instability in ovarian cancer.
SO - Anticancer Res 2002 Mar-Apr;22(2A):969-75
AD - Department of Obstetrics-Gynecology, Weill Medical College of Cornell University, New York, NY 10021, USA. Arziman@lycosmail.com
BACKGROUND: Molecular alterations such as DNA microsatellite instability (MSI/RER), single nucleotide polymorphism (SNP) and loss of heterozygosity (LOH) can occur throughout the genome and be associated with different types of cancer. In the present study, we aimed at detecting molecular alterations within the mismatch DNA repair genes in ovarian cancer (OC), using a sensitive, accurate and reliable protocol we have developed. MATERIALS AND METHODS: A combination of high-resolution GeneScan software analysis and automated DNA cycle sequencing was used. RESULTS: Negligible coding MSI was observed in selected sequences of mismatch DNA repair genes in our series of sixty-two ovarian tumors and matched blood DNAs. Unlike MSI, loss of one hMLH1 allele was scored in almost half (47%) of the informative cases. In addition, an SNP in hMSH3/intron 5 was found to be highly variable in OC patients. CONCLUSION: 1) Coding DNA instability is likely to be a very rare event in OC and, therefore, may not significantly contribute to the development of OC, and 2) the high frequency of LOH at hMLH1 observed in our ovarian tumors suggests that further investigation is needed to determine if such a trend exists in other mismatch DNA repair and/or critical genes.
UI - 11881387
AU - Iakimova TP; Dudnichenko AS; Kartashov SM
TI - [Structural and functional features of the ovaries as a risk factor for ovarian cancer in infertile women]
SO - Lik Sprava 2001 Sep-Dec;(5-6):73-6
In examining 502 female patients with cancer of the ovaries (OC) infertility was identified in 21.9 percent of cases. The prevalent form of infertility was tubal infertility (92.7%), there were but a few instances of the endocrine form (1.8%). The infertile women were studied for their hormonal and receptorial status (receptors of estradiol and progesterone). It has been established that women with the endocrine variant of infertility present with more prominent hormonal inadequacies in the hypophysis-ovaries system and manifest changes in the receptorial status of the ovaries than those with tubal infertility; the findings in the latter have not been shown to be different from controls. In endocrine infertility OC is in fact not encountered, which fact can be related to morphological features of the ovaries giving origin to endocrine disturbances, and to a decline in the receptorial status and absence of ovulation.
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