National Cancer Institute®
Last Modified: March 1, 2002
UI - 10995813
AU - Vergote I; Rustin GJ; Eisenhauer EA; Kristensen GB; Pujade-Lauraine E;
TI - Parmar MK; Friedlander M; Jakobsen A; Vermorken JB Re: new guidelines to evaluate the response to treatment in solid tumors [ovarian cancer]. Gynecologic Cancer Intergroup.
SO - J Natl Cancer Inst 2000 Sep 20;92(18):1534-5
UI - 11805587
AU - Harlap S; Olson SH; Curtin JP; Caputo TA; Nakraseive C; Sanchez D; Xue X
TI - Epithelial ovarian carcinoma and fertility of parents.
SO - Epidemiology 2002 Jan;13(1):59-65
AD - Department of Obstetrics and Gynecology, New York University School of Medicine, NY 10016, USA email@example.com.
We studied the fertility of the parents of 163 women with epithelial ovarian carcinoma in two hospitals in New York City, compared with the parents of 159 controls from similar neighborhoods. We used unconditional logistic regression to control for covariates, including parity, oral contraceptive use, age at menarche, and Jewish ancestry. Compared with women with zero or one sibling, those with two, three or four or more siblings had adjusted odds ratios (95% confidence intervals) of 0.91 (0.47-1.77), 0.61 (0.28-1.37), and 0.50 (0.26-0.98). On average, each additional sibling was associated with a risk reduction to 0.80 (0.66-0.98). These findings support the hypothesis that heritable conditions associated with reduced fertility of the subjects' parents may contribute to risk and may explain some of the effects of parity on the risk of this carcinoma. Alternatively, they may reflect some unidentified aspect of the environment experienced by girls growing up in small families. If confirmed in other data sets, these findings imply that sibship size might have confounded previous estimates of risk associated with a family history of cancer or with Jewish ethnicity.
UI - 11805588
AU - Vachon CM; Mink PJ; Janney CA; Sellers TA; Cerhan JR; Hartmann L; Folsom
TI - AR Association of parity and ovarian cancer risk by family history of breast or ovarian cancer in a population-based study of postmenopausal women.
SO - Epidemiology 2002 Jan;13(1):66-71
AD - Department of Health Sciences Research, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. firstname.lastname@example.org
Although parity is associated with a decreased risk of ovarian cancer in the general population, this association among women with a family history is less clear. We examined this question in a prospective cohort of 31,377 Iowa women 55-69 years of age at baseline. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated through Cox regression. We identified 181 incident epithelial ovarian cancers through 13 years of follow-up. At baseline, 14% of the women reported breast or ovarian cancer in a first-degree relative, and an additional 12% reported a family history in a second-degree relative. Among women without a family history of breast or ovarian cancer in a first-degree relative, nulliparous women were at slightly increased risk of ovarian cancer (RR = 1.4, 95% CI = 0.9-2.4) compared with parous women, whereas among women with a family history, nulliparous women were at a much higher risk (RR = 2.7, 95% CI = 1.1-6.6) than parous women. Similar results were seen when family history included first- or second-degree relatives with breast or ovarian cancer or a first- or second-degree relative with ovarian cancer only. Nulliparity may be more strongly associated with an increased risk of ovarian cancer among women with a family history of breast or ovarian cancer, compared with women who do not have a family history of those cancers.
UI - 11830553
AU - Liu JR; Opipari AW; Tan L; Jiang Y; Zhang Y; Tang H; Nunez G
TI - Dysfunctional apoptosome activation in ovarian cancer: implications for chemoresistance.
SO - Cancer Res 2002 Feb 1;62(3):924-31
AD - Department of Obstetrics and Gynecology, University of Michigan Medical School, L4000 Women's Hospital, 1500 East Medical Center Drive, Ann Arbor, MI 48109, USA. email@example.com
Alterations in the regulation of apoptosis may contribute to the pathogenesis of cancer and resistance of tumor cells to chemotherapy. In mammalian cells, nonreceptor-mediated apoptosis occurs predominantly via assembly of a cytochrome c-dependent apoptosome complex containing caspase-9 and apoptotic protease-activating factor-1 (Apaf-1). We show here that cytosolic extracts from human ovarian carcinoma cell lines and primary ovarian tumor samples are deficient in their ability to activate procaspase-9 in the presence of cytochrome c and dATP when compared with control extracts. SKOV3, a human ovarian carcinoma cell line with diminished apoptosome activity, was significantly more resistant to chemotherapy-induced apoptosis than cell lines with functional Apaf-1 activity. This dysfunctional apoptosome activity was not explained by reduced expression levels of caspase-9 or Apaf-1. Moreover, expression levels of known inhibitors of the apoptosome, including heat shock protein 70, heat shock protein 90, or X-linked inhibitor of apoptosis, did not correlate with functional activity of the apoptosome. SKOV3, an ovarian cancer cell line with dysfunctional apoptosome activity, retains the ability to form the Apaf-1 oligomer; however, there is a diminished amount of caspase-9 in the apoptosome. The reduction in the amount of caspase-9 in the apoptosome in the SKOV3 cell line was associated with diminished caspase-3 activity. Dysfunctional apoptosome activation may contribute both to the pathogenesis of ovarian carcinoma and to chemoresistance.
UI - 11748848
AU - Machackova E; Damborsky J; Valik D; Foretova L
TI - Novel germline BRCA1 and BRCA2 mutations in breast and breast/ovarian cancer families from the Czech Republic.
SO - Hum Mutat 2001 Dec;18(6):545
AD - Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno 656 53, Czech Republic.
Germline mutations in breast cancer susceptibility genes, BRCA1 and BRCA2, are responsible for a substantial proportion of high-risk breast and breast/ovarian cancer families. To characterize the spectrum of BRCA1 and BRCA2 mutations, we screened Czech families with breast/ovarian cancer using the non-radioactive protein truncation test, heteroduplex analysis and direct sequencing. In a group of 100 high-risk breast and breast/ovarian cancer families, four novel frame shift mutations were identified in BRCA1 and BRCA2 genes. In BRCA1, two novel frame shift mutations were identified as 3761-3762delGA and 2616-2617ins10; in BRCA2, two novel frame shift mutations were identified as 5073-5074delCT and 6866delC. Furthermore, a novel missense substitution M18K in BRCA1 gene in a breast/ovarian cancer family was identified which lies adjacent just upstream of the most highly conserved C3HC4 RING zinc finger motif. To examine the tertiary structure of the RING zinc finger domain and possible effects of M18K substitution on its stability, we used threading techniques according to the crystal structure of RAG1 dimerization domain of the DNA-binding protein. Copyright 2000 Wiley-Liss, Inc.
UI - 11773280
AU - Schildkraut JM; Calingaert B; Marchbanks PA; Moorman PG; Rodriguez GC
TI - Impact of progestin and estrogen potency in oral contraceptives on ovarian cancer risk.
SO - J Natl Cancer Inst 2002 Jan 2;94(1):32-8
AD - Department of Community and Family Medicine, Duke Comprehensive Cancer Center, Duke University Medical Center, Durham, NC 27710, USA. firstname.lastname@example.org
BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of developing ovarian cancer, but the mechanism for the risk reduction has not been well defined. In this study, we investigate the relationship between the progestin and estrogen potency in combination OCs and the risk of developing ovarian cancer. METHODS: The study included 390 case subjects with epithelial ovarian cancer and 2865 control subjects, between 20 and 54 years of age, identified from the Cancer and Steroid Hormone Study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between ovarian cancer risk and combination OC formulations while controlling for potential confounders. All statistical tests were two-sided. RESULTS: With users of high-progestin/high-estrogen potency OC as the referent group, users of low-progestin/high-estrogen potency formulations (adjusted OR = 2.1; 95% CI = 1.2 to 3.7) and low-progestin/low-estrogen potency formulations (adjusted OR = 1.6; 95% CI = 0.9 to 3.0) had a higher risk of ovarian cancer than users of high-progestin/high-estrogen potency formulation. Low-progestin potency OC formulations were associated with a statistically significant higher risk than high-progestin potency formulations (adjusted OR = 2.2; 95% CI = 1.3 to 3.9). This association was seen even among users of short duration. CONCLUSION: The combination OC formulations with high-progestin potency appear to be associated with a greater reduction in ovarian cancer risk than those with low-progestin potency. Mechanisms underlying this reduction may include inhibition of ovulation and/or some direct biologic effects of the progestin.
UI - 11773283
AU - Geisler JP; Hatterman-Zogg MA; Rathe JA; Buller RE
TI - Frequency of BRCA1 dysfunction in ovarian cancer.
SO - J Natl Cancer Inst 2002 Jan 2;94(1):61-7
AD - Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Holden Comprehensive Cancer Center, University of Iowa, Iowa City 52242, USA.
BACKGROUND: Ovarian cancer is one of the most common hereditary cancers in women. Mutations in the BRCA1 gene increase a woman's risk of ovarian cancer. Testing for BRCA1 mutations is cumbersome and impractical for large populations. Therefore, we developed an efficient strategy to detect various types of BRCA1 dysfunction and also determined the relative frequency of BRCA1 dysfunction in ovarian cancer. METHODS: Tumors from 221 patients with epithelial ovarian cancer were screened for loss of heterozygosity (LOH) at the BRCA1 locus. BRCA1 complementary DNA (cDNA) and genomic DNA from all cancers with BRCA1 LOH (106 tumors) or noninformative status (15 tumors) were polymerase chain reaction (PCR) amplified and analyzed for protein truncation in a coupled transcription/translation test. When truncated BRCA1 protein was detected, the BRCA1 gene from both the tumor and a paired blood sample was sequenced. When BRCA1 expression in tumor cDNA was not detected with a protein truncation test, a methylation-specific PCR was used to determine whether the promoter region of BRCA1 was methylated and thus inactivated. All statistical tests were two-sided. RESULTS: Fifty-one (23.1%) of 221 tumors had BRCA1 dysfunction, including 18 with germline mutations, 15 with somatic mutations, and 18 with monoallelic or biallelic hypermethylated promoters. By the consideration of only tumors with LOH or that were noninformative, the efficiency for detecting BRCA1 dysfunction improved to 45 (37.2%) of 121 tumors. Therefore, LOH/noninformative was a strong predictor of mutation status (Fisher's exact test, P<.001). However, this subset of tumors did not include those with BRCA1 missense mutations (estimated at six [2.7%] of 221 not detected by our method) or biallelic promoter methylation (estimated at six [2.7%] of 221). CONCLUSIONS: BRCA1 dysfunction in ovarian cancer is common and occurs via multiple mechanisms. The use of LOH, rather than a family history of ovarian cancer, as a first step in a screening strategy, followed by protein truncation testing, appears to increase the chance of identifying tumors with BRCA1 dysfunction.
UI - 11848020
AU - Czupkallo G; Jakowicki JA; Baranowski W
TI - [Stromal leydig cell tumor coexisting with ascites]
SO - Ginekol Pol 2001 Oct;72(10):825-8
AD - Oddzial Ginekologiczno-Polozniczy Szpitala SP ZOZ w Belzycach.
The stromal Leydig cell tumour (SLCT), a very rare, benign neoplasm was described in 75-year old woman. The patient presented the typical signs of virilisation (hirsutism, masculine alopecia, moderate clitoris enlargement, deep voice) as well as hypertension and insulin independent type of diabetes mellitus (IIDM). Additionally, she had marked ascites (3400 ml as established during surgery). The serum concentration of testosterone before the surgery was elevated up to 7.6 ng/ml. FSH and LH were at very low range (2.5 mIU/ml, 3.4 mIU/ml, respectively) whereas 17 beta-oestradiol was elevated (56 pg/ml). Total abdominal hysterectomy with salpingo-oophorectomy (TAH/BSO) and omentectomy were performed. The histopathological findings revealed stromal Leydig cell tumour with Reinke crystalloids. The postoperative follow-up was complicated by venous thrombosis. Five weeks after the surgery only slight regression of the signs of virilisation was observed. Hormonal findings were adequate to the patient age range (FSH--16.7 mIU/ml, LH--21.1 mIU/ml, testosterone--0.19 ng/ml, 17 beta-oestradiol concentration below 10 pg/ml).
UI - 11852993
AU - Pieretti M; Hopenhayn-Rich C; Khattar NH; Cao Y; Huang B; Tucker TC
TI - Heterogeneity of ovarian cancer: relationships among histological group, stage of disease, tumor markers, patient characteristics, and survival.
SO - Cancer Invest 2002;20(1):11-23
AD - Department of Pathology and Laboratory Medicine, University of Kentucky Medical Center, Lexington, USA. email@example.com
Epidemiological studies have established associations between various reproductive factors and risk of ovarian cancer; it has also been observed that some of these risk factors are only associated with specific histological subgroups. To investigate the correlation of genetic alterations with these risk factors, we examined a consecutive series of 158 ovarian cancer cases treated at the University of Kentucky (1990-96). Common molecular genetic alterations (LOH on chromosome 17, P53 alterations, K-RAS mutations), histological and clinical characteristics of the disease, demographic patient information and survival were evaluated. These latter data were from the Kentucky Cancer Registry. Univariate analysis showed higher frequencies of chromosome 17 loss and P53 mutations in tumors of advanced stage and grade, and in older and post-menopausal women. Non-mucinous tumors were more likely to be classified as late stage, high-grade cancers, and to have chromosome 17 loss and P53 mutations. Survival analysis indicated that stage was the only independent significant variable. When stage was the outcome variable in multiple logistic regression analysis, histology and chromosome 17 loss were significantly associated with poor survival. This case-case study provides evidence that ovarian cancers of mucinous and non-mucinous histology are significantly different with respect to clinical characteristics, survival and molecular alterations. It also lends support to the hypothesis that ovarian cancer is a heterogeneous disease with distinct etiological factors and clinical outcomes, which may require different approaches to treatment.
UI - 11857303
AU - Marth C; Kisic J; Kaern J; Trope C; Fodstad O
TI - Circulating tumor cells in the peripheral blood and bone marrow of patients with ovarian carcinoma do not predict prognosis.
SO - Cancer 2002 Feb 1;94(3):707-12
AD - Department of Obstetrics and Gynecology, Innsbruck University Hospital, Innsbruck, Austria. firstname.lastname@example.org
BACKGROUND: Ovarian carcinoma is apparently restricted for a long time to the peritoneal cavity. However, about 50% of patients with a surgically documented complete intraabdominal response experience later recurrence. Occult hematogenous micrometastases are common to most epithelial malignancies and have recently been found in 30% of bone marrow samples of ovarian carcinoma patients, as examined by immunocytochemistry. Moreover, these findings were associated with poor progression-free and overall survival. The aim of the current study was to evaluate the possible prognostic significance of tumor cells detected in the peripheral blood and bone marrow of ovarian carcinoma patients by an immunomagnetic method. METHODS: In a total of 90 patients with histologically proven epithelial ovarian carcinoma, blood and (in 73 cases) bone marrow samples were taken. Tumor cells were identified by a microbead coated with the antibody MOC-31, which recognizes an epitope regularly expressed on ovarian carcinoma cells. RESULTS: The authors detected carcinoma cells in the bone marrow in 21% of ovarian carcinoma patients, and in the peripheral blood in 12% of patients. Mean overall survival was 25 and 28 months for patients with or without circulating tumor cells, respectively. CONCLUSIONS: Ovarian carcinoma cells seem to reach peripheral circulation more frequently than expected. However, in contrast to an earlier report, detection of tumor cells in the bone marrow and/or blood was not associated with poor prognosis in ovarian carcinoma patients. This discrepancy remains unexplained, but characterization of circulating ovarian carcinoma cells for their malignant and metastatic capacity is clearly warranted. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10250
UI - 11859985
AU - Mogren I; Stenlund H; Hogberg U
TI - Long-term impact of reproductive factors on the risk of cervical, endometrial, ovarian and breast cancer.
SO - Acta Oncol 2001;40(7):849-54
AD - Department of Clinical Science, Umea University, Sweden. email@example.com
The influence of maternal age, parity, low or high birthweight, multiple births, and pre-eclampsia on the risk of cervical, endometrial, ovarian and breast cancers was studied. Data on 40951 women and the outcomes of their deliveries between 1955 and 1995 were obtained from birth registers. For the mothers, data from the Swedish Cancer Registry and the Cause of Death Register were added. The sample was evaluated using Cox's regression in univariate and bivariate analyses where the relative risk and its 95% confidence interval were calculated. Increasing maternal age at first birth was associated with an increasing relative risk of endometrial, ovarian, and breast cancers, and with a decreased risk of cervical cancer. Multiparity was a protective factor for all gynaecological cancers, including cervical and breast cancers. Multiple births were associated with an increased risk of endometrial cancer.
UI - 11812079
AU - Bao R; Selvakumaran M; Hamilton TC
TI - Targeted gene therapy of ovarian cancer using an ovarian-specific promoter.
SO - Gynecol Oncol 2002 Feb;84(2):228-34
AD - Ovarian Cancer Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
OBJECTIVES: The "suicide" gene therapy of cancer using promoters such as cytomegalovirus could cause severe toxicity to normal tissues due to a lack of specificity of prodrug activation. Therefore, we investigated gene therapy of ovarian cancer using ovarian-specific promoter (OSP1) to limit the synthesis of the prodrug activating enzyme HSVtk to ovarian cancer cells. METHODS: The HSVtk expressing plasmid pOSP1-HSVtk was created and transfected into an ovarian cancer cell line OVCAR3. The ganciclovir (GCV) sensitivity of the stable transfectants was evaluated with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tissue specificity of this promoter was evaluated by comparing the sensitivity to GCV between ovarian and nonovarian cancer cell lines after they were transfected with pOSP1-HSVtk. One transfectant sensitive to GCV was implanted intraperitoneally to immunocompromised mice which were treated subsequently with GCV. Furthermore, this ovarian cancer survival model was used to evaluate the in vivo efficacy of cationic lipid mediated pOSP1-HSVtk gene delivery followed by GCV treatment. RESULTS: Stable transfectants of OVCAR3 cells bearing OSP1-HSVtk became more sensitive to GCV treatment compared to the parental cell line and vector transfected OVCAR3 cell line. OSP1-HSVtk could specifically sensitize the OVCAR3 ovarian cancer cell line to GCV. SCID mice transplanted with the OVCAR3 transfectant and treated with GCV survived longer than the mice without GCV treatment (P = 0.032). In vivo gene delivery mediated by a cationic lipid (GL67) followed by GCV treatment yielded a longer survival in the OVCAR3 survival model (P = 0.016). CONCLUSIONS: The OSP1 promoter can selectively direct suicide gene therapy of ovarian cancer and the in vivo efficacy is improved by using a cationic lipid GL67 as delivery vehicle as opposed to the direct injection of plasmid. B)2001 Elsevier Science.
UI - 11812090
AU - Schiffenbauer YS; Meir G; Maoz M; Even-Ram SC; Bar-Shavit R; Neeman M
TI - Gonadotropin stimulation of MLS human epithelial ovarian carcinoma cells augments cell adhesion mediated by CD44 and by alpha(v)-integrin.
SO - Gynecol Oncol 2002 Feb;84(2):296-302
AD - Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
OBJECTIVE: The goal of this work was to evaluate the involvement of gonadotropins in the regulation of adhesion of human epithelial ovarian carcinoma. We studied two pathways that were previously implicated in the metastatic implantation of ovarian carcinoma to the peritoneum, namely hyaluronan-CD44 and RGD-integrin mediated adhesion. METHODS: Two cell lines derived from human epithelial ovarian carcinoma (MLS and OC238) were stimulated with luteinizing hormone (LH) and/or follicle stimulating hormone (FSH). Expression of CD44 was evaluated by Western blotting. Expression of alpha(v)-integrins was studied by RT-PCR and Northern blot. Integrin and CD44 mediated adhesion of the cells was analyzed using culture plates coated either with a thrombin derived RGD containing peptide or fibronectin for integrin mediated adhesion or with hyaluronan for CD44 mediated adhesion. RESULTS: MLS cells stimulated with either LH or FSH showed increased adhesion to culture plates coated with hyaluronan, as well as to culture plates coated with fibronectin or with a thrombin derived RGD containing peptide. In these cells, gonadotropin stimulation led to induced expression of the integrin subunit alpha(v) and CD44, the cell surface hyaluronan receptor. On the other hand, OC238 cells showed no expression of the integrin subunit alpha(v) and no hormonal effect on the expression of CD44. Accordingly, adhesion of OC238 cells on either RGD or CD44 was not affected by hormonal stimulation. CONCLUSION: Elevated levels of gonadotropins may in some cases facilitate peritoneal metastatic dissemination of ovarian cancer by increasing cell adhesion, the first essential step in the invasion process. B)2002 Elsevier Science.
UI - 11812093
AU - Eisenkop SM
TI - Thoracoscopy for the management of advanced epithelial ovarian cancer--a preliminary report.
SO - Gynecol Oncol 2002 Feb;84(2):315-20
AD - Women's Cancer Center, Encino-Tarzana, 5525 Etiwanda Ave., Suite 311, Tarzana, California 91356, USA. firstname.lastname@example.org
OBJECTIVE: To determine possible benefits of thoracoscopy for the management of patients with Stage IIIC and IV epithelial ovarian cancer. METHODS: Thirty patients underwent thoracoscopy at the time of primary cytoreduction to determine the presence and extent of intrathoracic disease and the feasibility of cytoreduction. Survival of patients with Stage IV disease undergoing thoracoscopy was compared to that of historical controls (Stage IV on the basis of positive pleural effusion cytology and/or pleural involvement by contiguous diaphragmatic metastases) who did not undergo thoracoscopy (log-rank analysis). RESULTS: Among the 24 patients with Stage IV disease having thoracoscopy, 11 (45.8%) did not have macroscopic intrathoracic disease, 10 (41.7%) underwent pleural implant ablation and/or excision as well as nodal excision that influenced the final cytoreductive outcome, and 3 (12.5%) had efforts to achieve complete intra-abdominal cytoreduction abbreviated after unresectable intrathoracic disease was found. The 24 patients who had thoracoscopy and the historical controls were not significantly different with respect to median age, performance status, extent of intra-abdominal disease, amount of ascites, and intra-abdominal cytoreductive outcome. The median and estimated 5-year survival for the entire cohort were 28.9 months and 42%, respectively. Log-rank analysis revealed the probability of survival to be improved by the performance of thoracoscopy (performed vs not performed, P = 0.05). CONCLUSIONS: Thoracoscopy quantifies the volume of intrathoracic disease, may allow abbreviation of the abdominal phase of cytoreduction for patients with unresectable pleural disease, and permits complete cytoreduction for some patients who might otherwise have unrecognized macroscopic residual intrathoracic disease. A multi-institutional prospective study may better define the role of this procedure in clinical practice. B)2002 Elsevier Science.
UI - 11848544
AU - Yen RF; Sun SS; Shen YY; Changlai SP; Kao A
TI - Whole body positron emission tomography with 18F-fluoro-2-deoxyglucose for the detection of recurrent ovarian cancer.
SO - Anticancer Res 2001 Sep-Oct;21(5):3691-4
AD - Department of Nuclear Medicine and PET Center National Taiwan University Hospital, Taipei.
Although many cancers can be detected by whole-body positron emission tomography (PET) with 18F-fluoro-2-deoxyglucose (FDG), there has been limited clinical experience with FDG-PET for the detection of recurrent ovarian cancers. Therefore, the aim of this study was to evaluate the clinical value of FDG-PET in the detection of recurrent ovarian cancer. Whole body FDG-PET scans were performed on 24 women who had previous histories of ovarian cancer and treatment with surgery and chemotherapy. All patients also underwent physical examination, laboratory testing of serum CA-125 level and pelvic-abdominal-chest computed tomography (CT) or magnetic resonance imaging (MRI). The results of FDG-PET scans were correlated with serum CA-125 level, CT/MRI and operative pathology results. The diagnostic sensitivity was 90.9%, 90.9% and 90.9%, specificity was 92.3%, 76.9% and 46.2% and accuracy was 91.7%, 83.3% and 66.7% for FDG-PET, serum tumor marker of CA-125 level and CT/MRI in detecting recurrent ovarian cancer, respectively. FDG-PET is a useful diagnostic tool in detecting recurrent ovarian cancers with high specificity as compared with the serum tumor marker CA-125 level and the conventional CT/MRI morphological imaging methods.
UI - 11848553
AU - Scholz HS; Benedicic C; Haas J; Tamussino K; Petru E
TI - Stage IV ovarian cancer: prognostic factors and survival beyond 5 years.
SO - Anticancer Res 2001 Sep-Oct;21(5):3729-32
AD - Department of Obstetrics and Gynecology, University of Graz, Austria. email@example.com
BACKGROUND: Ovarian cancer continues to be the leading cause of death due to gynecologic malignancies and most patients still present with advanced disease. In the present study we evaluated long-term survival and prognostic factors in patients with stage IV ovarian cancer. PATIENTS AND METHODS: The charts of 62 consecutive women with FIGO stage IV epithelial ovarian cancer were reviewed. RESULTS: Chemotherapy was the only factor associated with longer survival. Three patients (5%) survived for longer than 5 years. One died of disease at 6.3 years and two are alive without evidence of disease at 12.4 and 14.9 years, respectively. CONCLUSION: Survival seemed to correlate with the possibility of administering chemotherapy. Patients with verified stage IV ovarian cancer, in whom due to the initial tumor load, operative extent and concomitant illness, the possibility of postoperative chemotherapy administration seems questionable, might be considered for primary chemotherapy followed by surgery.
UI - 11870520
AU - O'Doherty AM; Church SW; Russell SE; Nelson J; Hickey I
TI - Methylation status of oestrogen receptor-alpha gene promoter sequences in human ovarian epithelial cell lines.
SO - Br J Cancer 2002 Jan 21;86(2):282-4
AD - School of Biology and Biochemistry, The Queen's University of Belfast, Lisburn Road, Belfast, Northern Ireland, UK.
We have determined the methylation status of the CpG island of the oestrogen receptor alpha gene in seven human ovarian cell lines. Cell lines expressing oestrogen receptor alpha showed no evidence of hypermethylation. In three of four cell lines that produced no detectable oestrogen receptor alpha protein, hypermethylation was observed at the NotI site of the CpG island. These results indicate that aberrant hypermethylation may be responsible for a significant proportion of epithelial ovarian tumours in which oestrogen receptor alpha expression is lost. Copyright 2002 The Cancer Research Campaign
UI - 11845216
AU - Dibble SL; Roberts SA; Robertson PA; Paul SM
TI - Risk factors for ovarian cancer: lesbian and heterosexual women.
SO - Oncol Nurs Forum 2002 Jan-Feb;29(1):E1-7
AD - Institute for Health and Aging in the School of Nursing, University of California, San Francisco, CA, USA. firstname.lastname@example.org
PURPOSE/OBJECTIVES: To compare the distribution of risk factors for developing ovarian cancer in lesbian and heterosexual women. DESIGN: Secondary analysis of a retrospective medical record review. SETTING: Urban health clinic with special outreach to lesbians. SAMPLE: Typical participant (N = 1,019) was 42.9 years old and white (70%). Most were without health insurance, and 99% were poor (< $15,780 annual income). The majority (58%, n = 586) described themselves as heterosexual; 42% (n = 433) said they were lesbian. METHODS: Data were collected from medical records and analyzed using analysis of covariance and logistic regression techniques. MAIN RESEARCH VARIABLES: Ovarian cancer risk factors (parity, exogenous hormone use, smoking, body mass index [BMI], and tubal ligation/hysterectomy). FINDINGS: Lesbians had a higher BMI; heterosexual women had higher rates of current smoking and a higher incidence of the protective factors of pregnancy, children, miscarriages, abortions, and use of birth control pills. CONCLUSIONS: The results of this study indicate that lesbians may have an increased risk for developing ovarian cancer. A study designed specifically to explore the risk factors of lesbian and heterosexual women for developing ovarian cancer must be undertaken to confirm these findings. IMPLICATIONS FOR NURSING PRACTICE: Differences in risk levels may exist for lesbians; therefore, healthcare providers must become comfortable asking questions about sexual orientation and behavior.
UI - 11815406
AU - Bonadona V; Saltel P; Desseigne F; Mignotte H; Saurin JC; Wang Q;
TI - Sinilnikova O; Giraud S; Freyer G; Plauchu H; Puisieux A; Lasset C Cancer patients who experienced diagnostic genetic testing for cancer susceptibility: reactions and behavior after the disclosure of a positive test result.
SO - Cancer Epidemiol Biomarkers Prev 2002 Jan;11(1):97-104
AD - Unit of Prevention and Genetic Epidemiology, Comprehensive Cancer Center Leon Berard, 28 rue Laennec, 69008 Lyon, France.
The aim of this prospective study was to evaluate the consequences of the disclosure of a positive genetic test result to patients affected with cancer. Personal repercussions and patients' behavior with the transmission of their results to relatives were considered. We conducted semistructured interviews with 23 cancer patients identified as carriers of a cancer-predisposing mutation for hereditary breast ovarian or nonpolyposis colorectal cancers, 1 month after the disclosure of the test result. Eight patients spontaneously expressed distressed reactions ("you no longer feel cured"), and 14 patients reported at least one negative feeling (dissatisfied, discouraged, unhappy, or worried), despite expecting to be a carrier. Sixteen patients expressed concerns about the risk of developing another cancer, and 18 were concerned for their children's future, in that they may carry the mutation and develop a cancer. Although 8 patients found that disadvantages of knowing their genetic status outweighed the advantages, all but 1 did not regret having undergone genetic testing. All of the patients transmitted their results to at least one close relative. Although 6 of them expressed difficulties in being the only person who could transmit the information and 9 said it was a heavy responsibility, all except 1 did not want someone else to have to inform their families. Our results illustrate the potential negative impact of diagnostic genetic testing in patients with cancer. This includes distressed reactions and difficulties in transmitting their results to relatives. Future large-scale studies are warranted to confirm our findings.
UI - 11821091
AU - Dor J; Lerner-Geva L; Rabinovici J; Chetrit A; Levran D; Lunenfeld B;
TI - Mashiach S; Modan B Cancer incidence in a cohort of infertile women who underwent in vitro fertilization.
SO - Fertil Steril 2002 Feb;77(2):324-7
AD - Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer 52621, Israel.
OBJECTIVE: To assess whether ovarian hyperstimulation and IVF increase the risk for cancer. DESIGN: Historical cohort analysis. SETTING; IVF units of two medical centers in Israel. PATIENT(S): Five thousand twenty-six women who underwent IVF between 1981 and 1992. INTERVENTION(S); Cancer incidence rates were determined through linkage to the National Cancer Registry and were compared with expected rates with respect to age, sex, and place of birth. MAIN OUTCOME MEASURE(S): Development of cancer. RESULT(S): Twenty-seven cases of cancer were observed, and 35.6 were expected (standardized incidence ratio, 0.76 [95% CI, 0.50-1.10]). Eleven cases of breast cancer were observed, whereas 15.86 were expected (standardized incidence ratio, 0.69 [95% CI, 0.46-1.66]). One case of ovarian cancer and 1 case of cervical cancer were observed, compared with 1.74 and 1.73 cases expected, respectively. The type of infertility, number of IVF cycles, and treatment outcome did not significantly affect risk for cancer. CONCLUSION(S): In a cohort of women treated with IVF, no excess risk for cancer was noted.
UI - 11786575
AU - Ben David Y; Chetrit A; Hirsh-Yechezkel G; Friedman E; Beck BD; Beller
TI - U; Ben-Baruch G; Fishman A; Levavi H; Lubin F; Menczer J; Piura B; Struewing JP; Modan B; National Israeli Study of Ovarian Cancer Effect of BRCA mutations on the length of survival in epithelial ovarian tumors.
SO - J Clin Oncol 2002 Jan 15;20(2):463-6
AD - Department of Gynecology, Haemek Medical Center, Afula.
PURPOSE: To study the role of BRCA mutations in ovarian cancer survival. PATIENTS AND METHODS: Blood samples and specimens of ovarian tumors (whenever blood samples were not available) at the time of the primary surgery were obtained in the course of a nationwide case-control study of women with ovarian cancer in Israel. The three common BRCA mutations in Israel (185delAG, 5382insC, and 6174delT) were analyzed with a multiplex polymerase chain reaction to amplify the exons containing the three mutations using fluor-labeled primers in a single reaction. Because each mutation is a small insertion or deletion, they can be detected as length polymorphisms. Patients were followed for up to 5 years (range, 20 to 64 months). Statistical analysis was performed using the Kaplan-Meier method and the log-rank test. Stepwise Cox regression analysis was used for determination of independent prognostic factors. RESULTS: This report is based on 896 blood or tumor specimens analyzed for the presence of the BRCA mutations. Of these, 234 women (26.1%) were found to be positive. A significant difference in survival pattern was found between BRCA1/BRCA2 carriers and noncarriers among the women with invasive ovarian cancer (median survival, 53.4 months v. 37.8 months; 3-year survival, 65.8% v. 51.9%, respectively). These differences were independent of age at diagnosis or stage of the disease. CONCLUSION: Our data indicate that the survival of patients with ovarian cancer is affected by BRCA germline mutation, at least in the early years after diagnosis.
UI - 11829379
AU - Leeson S; Iredale R; Stansfield K; Evans A; Gray J
TI - Developing a cancer genetics service in Wales: opinions of gynaecologists on the management of women at risk of familial ovarian cancer.
SO - Eur J Cancer Care (Engl) 2001 Sep;10(3):172-8
AD - Department of Obstetrics and Gynaecology, Ysbyty Gwynedd, North Wales, UK.
In Wales, a cancer genetics service has been developing since 1998. Gynaecologists play an integral role in the management of women with a family history of ovarian cancer and we were interested in investigating referral practice and management for relatives of patients with ovarian cancer among gynaecologists in Wales. In 1999, a postal questionnaire was sent to all gynaecologists. The response rate was 51%. The questionnaire contained structured questions about current provision and a number of hypothetical scenarios to explore referral patterns to the cancer genetics service. The results of this study showed that referrals varied widely among specialists, as did the numbers who required onward referral to cancer genetics. The offer of screening to women at high risk of ovarian cancer was consistent, although there were variations in how often it was offered and the age at which it was offered. Most gynaecologists were easily able to establish when it was appropriate to refer onwards to cancer genetics, differentiating between women at high or low risk. There was some confusion about women at moderate risk of ovarian cancer. This study demonstrated the need for clear referral guidelines in Wales. Guidelines have since been distributed to all general practitioners and specialists; however, continued monitoring and further evaluation of referral practices will be necessary.
UI - 11844820
AU - Kolomainen DF; Larkin JM; Badran M; A'Hern RP; King DM; Fisher C;
TI - Bridges JE; Blake PR; Barton DP; Shepherd JH; Kaye SB; Gore ME Epithelial ovarian cancer metastasizing to the brain: a late manifestation of the disease with an increasing incidence.
SO - J Clin Oncol 2002 Feb 15;20(4):982-6
AD - Gynaecology Unit, Royal Marsden Hospital, London, United Kingdom.
PURPOSE: We present the Royal Marsden Hospital experience of cerebral metastases from primary epithelial ovarian carcinoma (EOC) over the last 20 years and examine the evidence for an increasing incidence of EOC metastasizing to this site. PATIENTS AND METHODS: A total of 3,690 women with EOC were seen at the Royal Marsden Hospital from 1980 to 2000. Eighteen of these patients developed cerebral metastases. RESULTS: Median age at diagnosis of EOC was 52 years (range, 39 to 67). All patients received at least one line of platinum-based chemotherapy; 56% (10 of 18) received more than one line of treatment; 17% (three of 18), two lines; 11% (two of 18), three lines; and 28% (five of 18), four lines. The median treatment interval between each line of chemotherapy was 12, 18, and 4 months. The median interval between diagnosis and CNS relapse was 46 months (range, 12 to 113), in comparison with 5 and 7.5 months for hematogenous relapse in lung or liver, respectively (P <.001). The incidence of CNS metastases in our population from 1980 to 1984 was 0.2%; from 1985 to 1989, 0%; from 1990 to 1994, 0.3%; and from 1995 to 1999, 1.3% (P <.001). An analysis of data from the literature also suggests that the incidence of cerebral metastases from EOC has increased over time. CONCLUSION: CNS metastases in EOC are a rare and late manifestation of the disease, occurring in patients with a prolonged survival caused by repeated chemosensitive relapses. An analysis of our data and the data from the literature suggests that the incidence of metastasis at this site in patients with EOC is increasing.
UI - 11855877
AU - McGuire V; Jesser CA; Whittemore AS
TI - Survival among U.S. women with invasive epithelial ovarian cancer.
SO - Gynecol Oncol 2002 Mar;84(3):399-403
AD - Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California 94305-5405, USA. email@example.com
OBJECTIVE: Invasive epithelial ovarian cancer is a highly fatal disease, diagnosed at advanced stages when survival is poor. Relatively little is known about the variation in survival across U.S. women of different race/ethnicities. To investigate this issue, we evaluated pathological characteristics and death rates due to invasive epithelial ovarian cancer in a population-based sample of patients from six racial/ethnic groups. METHODS: The analysis included 38,012 women diagnosed with primary invasive epithelial ovarian cancer between 1973 and 1997 in the Surveillance, Epidemiology and End Results Program of the National Cancer Institute. RESULTS: Filipina patients were younger at diagnosis, more likely to have localized disease, and had more mucinous cancers than whites. African-Americans were more likely than whites to be diagnosed at older ages, with distant disease and with undifferentiated/unclassified cancers. After adjusting for age at diagnosis, stage of disease at diagnosis, and cancer histology, we found that, compared to whites, death rates were significantly elevated among African-Americans and significantly reduced among Hispanics and Filipina. We also found that death rates declined significantly with time since diagnosis among women with advanced disease. CONCLUSION: The declining death rates in women with advanced disease suggest the presence of considerable prognostic heterogeneity among these women, which could reflect differences in quality of care. This issue, as well as the survival disadvantage for African-American women and survival advantages for Hispanic and Filipina women, needs investigation.
UI - 11855878
AU - Kolfschoten GM; Hulscher TM; Schrier SM; van Houten VM; Pinedo HM; Boven
TI - E Time-dependent changes in factors involved in the apoptotic process in human ovarian cancer cells as a response to cisplatin.
SO - Gynecol Oncol 2002 Mar;84(3):404-12
AD - Department of Medical Oncology, Vrije Universiteit Medical Centre, Amsterdam, the Netherlands.
OBJECTIVES: Apoptosis is believed to be a major mechanism of cisplatin-induced cell death. We investigated the kinetics of apoptosis in four human ovarian cancer cell lines treated with cisplatin to obtain insight into the role and the behavior of a variety of factors involved in this process. METHODS: The cell lines A2780, H134, and IGROV-1 (all wild-type p53) and OVCAR-3 (mutant p53) were exposed to cisplatin for 1 h and the antiproliferative effects were measured after 96 h. At various time points up to 96 h after the 1-h exposure to the individual 90% growth-inhibiting cisplatin concentrations, FACS analysis and May-Grunwald Giemsa staining were carried out to determine the extent of apoptosis. At the same time points protein expression levels of p53, p21/WAF1, Bax, and Bcl-2 and the activity of caspase-3 were measured. FACS analysis was also carried out to determine changes in cell cycle distribution as a response to cisplatin. RESULTS: The four cell lines differed in sensitivity to cisplatin. A2780 was the most sensitive and IGROV-1 was the least sensitive. In contrast, IGROV-1 cells showed the highest percentage of apoptosis (30-40%), while A2780 had the lowest percentage (6-14%) (r = 0.99). The occurrence of apoptosis was not dependent on functional p53. Of interest, caspase-3 activity was in line with the percentage of apoptosis and preceded DNA fragmentation and the visualization of condensed nuclei. Wild-type p53 cells accumulated in the S phase, while OVCAR-3 arrested in the G2/M phase. The protein expression levels of p53, p21/WAF1, Bax, and Bcl-2 varied in time, but were not related to the apoptotic behavior of the cells. Upregulation of p53 was already evident before activation of caspase-3. CONCLUSIONS: Time-dependent changes in the various factors involved in the apoptotic process induced by equitoxic doses of cisplatin vary strongly among the cell lines. Caspase-3 activation plays an important role in cisplatin-induced apoptosis and this precedes morphological changes. The ability of cells to enter apoptosis, however, does not seem to predict sensitivity to cisplatin.
UI - 11855879
AU - Leitao M; Boyd J
TI - Preoperative CA-125 levels in patients with hereditary compared to sporadic epithelial ovarian carcinoma.
SO - Gynecol Oncol 2002 Mar;84(3):413-5
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
OBJECTIVE: The aim of this study was to determine whether a significant difference in preoperative CA-125 levels exists between patients with BRCA-associated hereditary ovarian carcinoma and those with sporadic ovarian carcinoma and whether the CA-125 level predicts the probability of optimal cytoreductive surgery. METHODS: From a retrospective cohort of 189 consecutive ovarian cancer patients genotyped for BRCA mutation status, data on preoperative CA-125 levels were available for 49/88 (56%) hereditary cases and 43/101 (43%) sporadic cases. Data on the extent of surgical cytoreduction were obtained for all 92 patients with available CA-125 data. Comparison of preoperative CA-125 levels between hereditary and sporadic groups was assessed using the Kruskal-Wallis chi(2) test. Correlation of surgical cytoreduction with preoperative CA-125 level was assessed using Fisher's exact test. RESULTS: Mean preoperative CA-125 levels were not significantly different among BRCA1 (2289 U/ml), BRCA2 (2586 U/ml), and sporadic (3307 U/ml) cases (P = 0.5). For hereditary cases, optimal cytoreduction was achieved in 59% of patients with preoperative CA-125 levels of <500 U/ml