National Cancer Institute®
Last Modified: February 1, 2002
UI - 11745676
AU - Evans MF; Herrington CS
TI - Allelic imbalance is not restricted to numerically abnormal chromosomes in epithelial ovarian tumours.
SO - J Pathol 2001 Nov;195(4):443-50
AD - Department of Pathology, Duncan Building, Royal Liverpool University Hospital, Daulby Street, Liverpool L69 3GA, Merseyside, UK.
In this study, 23 low malignant potential (LMP) and 27 invasive epithelial ovarian tumours have been examined by microdissection and microsatellite polymerase chain reaction (PCR) for allelic imbalance (AI) at loci on the p and q arms of chromosomes 1, 11, 17, and X, and the data have been compared with interphase cytogenetics for numerical abnormalities (aneusomy) of these chromosomes. AI was uncommon in LMP tumours (5 of 23 at 9 of 146 informative loci) but was significantly more common (p<0.001) in invasive carcinomas (21 of 27 at 47 of 168 informative loci). This difference remained when LMP tumours were compared specifically with stage I carcinomas (p<0.001). A greater number of loci were involved in AI amongst serous than amongst mucinous carcinomas (p=0.015). AI was present at significantly more loci in carcinomas showing aneusomy by interphase cytogenetics than in those showing no numerical chromosome abnormalities (p<0.001). However, amongst the carcinomas showing aneusomy, AI was as frequent at loci on chromosomes with no numerical abnormality as at those with the numerical changes. These data demonstrate that aneusomy and AI are interrelated phenomena but that AI does not occur simply as a consequence of numerical chromosome changes. Copyright 2001 John Wiley & Sons, Ltd.
UI - 11745677
AU - Piek JM; van Diest PJ; Zweemer RP; Jansen JW; Poort-Keesom RJ; Menko FH;
TI - Gille JJ; Jongsma AP; Pals G; Kenemans P; Verheijen RH Dysplastic changes in prophylactically removed Fallopian tubes of women predisposed to developing ovarian cancer.
SO - J Pathol 2001 Nov;195(4):451-6
AD - Department of Obstetrics and Gynaecology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
The aim of this study was to investigate the occurrence of (pre)neoplastic lesions in overtly normal Fallopian tubes from women predisposed to developing ovarian carcinoma. The presence of (pre)neoplastic lesions was scored in histological specimens from 12 women with a genetically determined predisposition for ovarian cancer, of whom seven tested positive for a germline BRCA1 mutation. A control group included 13 women. Immunohistochemistry was used to determine the expression of p21, p27, p53, cyclin A, cyclin D1, bcl-2, Ki67, HER-2/neu, and the oestrogen and progesterone receptors. Loss of heterozygosity (LOH) analysis on the BRCA1 locus was also assessed on dysplastic tissue by PCR studies. Of the 12 women with a predisposition for ovarian cancer, six showed dysplasia, including one case of severe dysplasia. Five harboured hyperplastic lesions and in one woman no histological aberrations were found in the Fallopian tube. No hyperplastic, dysplastic or neoplastic lesions were detected in the Fallopian tubes of control subjects. In the cases studied, morphologically normal tubal epithelium contained a higher proportion of Ki67-expressing cells (p=0.005) and lower fractions of cells expressing p21 (p<0.0001) and p27 (p=0.006) than in the control group. Even higher fractions of proliferating cells were found in dysplastic areas (p=0.07) and accumulation of p53 was observed in the severely dysplastic lesion. Expression patterns of other proteins studied, including the hormone receptors, were similar in cases and controls. One subject, a germline BRCA1 mutation carrier, showed loss of the wild-type BRCA1 allele in the severely dysplastic lesion. In conclusion, the Fallopian tubes of women predisposed to developing ovarian cancer frequently harbour dysplastic changes, accompanied by changes in cell-cycle and apoptosis-related proteins, indicating an increased risk of developing tubal cancer. Copyright 2001 John Wiley & Sons, Ltd.
UI - 11751427
AU - Riva F; Zuco V; Vink AA; Supino R; Prosperi E
TI - UV-induced DNA incision and proliferating cell nuclear antigen recruitment to repair sites occur independently of p53-replication protein A interaction in p53 wild type and mutant ovarian carcinoma cells.
SO - Carcinogenesis 2001 Dec;22(12):1971-8
AD - Centro di Studio per l'Istochimica del CNR, Piazza Botta 10, 27100 Pavia, Italy.
The tumour suppressor gene TP53 plays an important role in the regulation of DNA repair, and particularly of nucleotide excision repair. The influence of p53 status on the efficiency of the principal steps of this repair pathway was investigated after UV-C irradiation in the human ovarian carcinoma cell line IGROV-1 (expressing wild-type p53) and in the derived clone IGROV-1/Pt1 (with p53 mutations at codons 270 and 282). Clonogenic survival after UV-C irradiation showed that IGROV-1/Pt1 cells were approximately 2-fold more resistant to DNA damage than parental cells. Modulation of p53 protein levels, cell cycle arrest and apoptosis were induced in UV-irradiated IGROV-1 cells, but not in the p53-mutant cell line. Exposure to UV or cisplatin induced down-regulation of p53-replication protein A (RPA) interaction in parental, but not in IGROV-1/Pt1 cells. However, persistent binding of p53 to RPA did not affect the early steps of DNA repair. In fact, both UV-induced DNA incision and the recruitment of proliferating cell nuclear antigen (PCNA) to DNA repair sites occurred to a comparable extent in p53-wild type and -mutant cell lines, although PCNA remained associated with chromatin for a longer period of time in IGROV-1/Pt1 cells. Global genome repair, as detected by immunoblot analysis of cyclobutane pyrimidine dimers, was not significantly different in the two cell lines at 3 h after UV irradiation. In contrast, lesion removal at 24 h was markedly reduced in IGROV-1/Pt1 cells, being approximately 25% of the initial amount of damage, as compared with approximately 50% repair in parental cells. These results indicate that the presence of mutant p53 protein and its persistent interaction with RPA do not affect the early steps of nucleotide excision repair in IGROV-1/Pt1 cells. Thus, repair defects in p53-mutant ovarian carcinoma cells may be attributed to late events, possibly related to a reduced removal/recycling of PCNA at repair sites.
UI - 11786728
AU - Hovig E; Rye PD; Warren DJ; Nustad K
TI - CA 125: the end of the beginning.
SO - Tumour Biol 2001 Nov-Dec;22(6):345-7
AD - Central Laboratory, Norwegian Radium Hospital, Oslo, Norway.
CA 125, a high-molecular-weight mucin, was first defined in 1981 by the monoclonal antibody OC125. Until recently, it has defied many attempts to purify it from a variety of sources, although many research groups have successfully raised antibodies that bind to CA 125. Nevertheless, CA 125 has demonstrated its considerable value as a marker in monitoring patients with ovarian cancer. This year, two research groups have succeeded in cloning the high-molecular-weight mucin CA 125. Their findings are summarized and the significance discussed in light of existing data from the human genome. Copyright 2001 S. Karger AG, Basel
UI - 11786729
AU - O'Brien TJ; Beard JB; Underwood LJ; Dennis RA; Santin AD; York L
TI - The CA 125 gene: an extracellular superstructure dominated by repeat sequences.
SO - Tumour Biol 2001 Nov-Dec;22(6):348-66
AD - Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. firstname.lastname@example.org
CA 125 has long presented problems to both clinicians and investigators because there was no definitive information on its structure and function. Here, we describe our work on cloning the CA 125 gene with the anticipation that such information will provide the basis for understanding its structure and its physiologic role in both normal and malignant tissues. The CA 125 protein core is composed of a short cytoplasmic tail, a transmembrane domain and an extraordinarily large glycosylated extracellular structure. This structure is dominated by a repeat domain composed of 156 amino acid repeat units which encompass the epitope binding sites. The molecule also includes an amino terminal domain of serine/threonine-rich sequences which would account for most of the O-glycosylation known to be present in CA 125. CA 125 is an unusually large transmembrane glycoprotein. Its release from the surface of the cell is most probably dependent on cytoplasmic phosphorylation followed by proteolytic cleavage. The extracellular domain is characterized by a large number of repeat units (probably 60+) which encompass an interactive disulfide bridged cysteine-loop and the site of OC125 and M11 binding. Sequencing the gene provides us with the ability to initiate the quest to understand the biological function of CA 125. Copyright 2001 S. Karger AG, Basel
UI - 11780384
AU - Pan L; Tong Y; Jin Y; Zhou S; Zhang Y; Yang X; Mao N
TI - Reversing drug resistance in the ovarian carcinoma cell line SKOV3/mdr1 in vitro by antisense oligodeoxynucleotides.
SO - Chin Med J (Engl) 2001 Sep;114(9):929-32
AD - Department of Obstetrics and Gynecology, Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing 100730, China.
OBJECTIVE: To investigate the effect of multidrug resistance gene 1 (mdr1) antisense oligodeoxynucleotides (ODNs) on reversing multidrug resistance in the drug resistant ovarian carcinoma cell line SKOV3/mdr1. METHODS: The ovarian carcinoma cell line SKOV3 transducted with a human multidrug resistance gene (mdr1) served as the drug resistant model (SKOV3/mdr1). The mdr1 antisense ODNs was transfected into SKOV3/mdr1 cells while mediated by lipofectamine. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression and the amount of the mdr1 mRNA in the cells. The positive rate and function of the mdr1 gene product P-glycoprotein (Pgp) in the mdr1 antisense ODNs treated SKOV3/mdr1 cells were determined by flow cytometry and rhodamine 123 efflux. Drug resistance in the SKOV3/mdr1 cell line was observed by MTT assay and cell colony culture. RESULTS: The mdr1 mRNA level was decreased to about 60% of that of beta-actin after mdr1 antisense ODNs treatment. The Pgp positive rate of mdr1 antisense ODNs treated SKOV3/mdr1 cells decreased from 100% to 52.6% (P < 0.01). The intracellular rhodamine 123 retention was increased from 9.1% to 33.8% (P < 0.01). The chemoresistance to taxol decreased to 58% of SKOV3/mdr1 with mdr1 antisense ODN treatment. Compared with SKOV3/mdr1 cells in the control group, under a certain range of drug concentrations, the number of drug resistance colonies in mdr1 antisense ODNs treated SKOV3/mdr1 cells for taxol and doxorubicin decreased by 8.6 +/- 0.8 fold and 3.1 +/- 0.6 fold, respectively. Some non-specific functions during oligodeoxyncleotide treatment was also detected. CONCLUSION: mdr1 expression in the SKOV1/mdr1 cell line was partially inhibited after mdr1 antisense ODNs treatment at the mRNA and protein level, increasing the chemotherapy sensitivity of this drug resistant ovarian carcinoma cell line.
UI - 11554664
AU - Young RH
TI - Guest editor's introduction. Ovarian tumors: perplexing patterns, perspicacious pathologists.
SO - Semin Diagn Pathol 2001 Aug;18(3):155-60
AD - James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, USA.
UI - 11554665
AU - Young RH; Scully RE
TI - Differential diagnosis of ovarian tumors based primarily on their patterns and cell types.
SO - Semin Diagn Pathol 2001 Aug;18(3):161-235
AD - James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Harvard Medical School, Boston, USA.
The differential diagnosis of ovarian tumors is reviewed based on their patterns and cell types. This approach, which differs from the standard textbook discussion of each neoplasm as an entity, has practical value as differential diagnosis depends largely on the pattern or patterns and cell type or types of tumors. Awareness of the broad range of lesions that may exhibit particular patterns or contain one or more cell types is crucial in formulating a differential diagnosis. The following patterns are considered: moderate-to-large-glandular and hollow-tubular; solid tubular and pseudotubular; cords and ribbons; insular; trabecular; slit-like and reticular spaces; microglandular and microfollicular; macrofollicular and pseudomacrofollicular; papillary; diffuse; fibromatous-thecomatous; and biphasic and pseudobiphasic. The following cell types are considered: small round cells; spindle cells; mucinous cells, comprising columnar, goblet cell and signet ring cell subtypes; clear cells; hobnail cells; oxyphil cells; and transitional cells. The morphologic diversity of ovarian tumors poses many challenges; knowledge of the occurrence and frequency of these patterns and cell types in various tumors and tumor-like lesions is of paramount diagnostic importance. A specific diagnosis can usually be made by evaluating routinely stained slides, but much less often, special staining, immunohistochemical staining or, very rarely, ultrastructural examination is also required. Finally, clinical data, operative findings, and gross features of the lesions may provide important, and at times decisive diagnostic clues.
UI - 10885351
AU - Meijers-Heijboer EJ; Verhoog LC; Brekelmans CT; Seynaeve C;
TI - Tilanus-Linthorst MM; Wagner A; Dukel L; Devilee P; van den Ouweland AM; van Geel AN; Klijn JG Presymptomatic DNA testing and prophylactic surgery in families with a BRCA1 or BRCA2 mutation.
SO - Lancet 2000 Jun 10;355(9220):2015-20
AD - Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes highly predispose to breast and ovarian cancer. In families with BRCA1 or BRCA2 mutations, identification of mutation carriers is clinically relevant in view of the options for surveillance and prevention. METHODS: We assessed presymptomatic DNA testing and prophylactic surgery in 53 consecutive families presenting to the Rotterdam Family Cancer Clinic with a known BRCA1 or BRCA2 mutation. We identified predictors for DNA testing and prophylactic surgery with univariate and multivariate analysis. FINDINGS: 682 unaffected individuals with a 50% risk (275 women and 271 men) or with a 25% risk (136 women) for carrying a mutation were identified and offered a DNA test. Presymptomatic DNA testing was requested by 48% (198 of 411) of women and 22% (59 of 271) of men (odds ratio for difference between sexes 3.21 [95% CI 2.27-4.51]; p<0.001). In women, DNA testing was significantly more frequent at young age, in the presence of children, and at high pre-test genetic risk for a mutation. Of the unaffected women with an identified mutation who were eligible for prophylactic surgery, 51% (35 of 68) opted for bilateral mastectomy and 64% (29 of 45) for oophorectomy. Parenthood was a predictor for prophylactic mastectomy but not for prophylactic oophorectomy. Age was significantly associated with prophylactic oophorectomy, but not with prophylactic mastectomy, although there was a tendency towards mastectomy at younger ages. INTERPRETATION: In a clinical setting, we show a high demand for BRCA1 and BRCA2 testing by unaffected women at risk, and of prophylactic surgery by unaffected women with the mutation. Young women with children especially opt for DNA testing and prophylactic mastectomy.
UI - 11499060
AU - Frank TS; Critchfield GC
TI - Identifying and managing hereditary risk of breast and ovarian cancer.
SO - Clin Perinatol 2001 Jun;28(2):395-406
AD - Myriad Genetic Laboratories, Salt Lake City, Utah, USA. email@example.com
In the past, all women with a family history of breast or ovarian cancer were considered to be at increased risk of cancer themselves. The discovery of BRCA1 and BRCA2 demonstrated that susceptibility to breast and ovarian cancer can be inherited by women as a single-gene autosomal dominant disorder. For such women, evaluation of family history is an important screening tool to identify the possibility of hereditary cancer risk but only genetic testing can provide definitive, individualized risk assessment. Women who have inherited mutations in BRCA1 or BRCA2 now have several medical management options to address their increased risk of cancer. A well-educated community of health care providers and patients can use hereditary risk assessment, including genetic testing, to improve health care.
UI - 11775215
AU - Jiang C; Tan Y; Li E; Zhang D
TI - Neuroendocrine differentiation in ovarian mucinous tumors.
SO - Chin Med J (Engl) 2000 Jan;113(1):70-4
AD - Department of Pathology, Tianjin Medical University, Tianjin 300070, China.
OBJECTIVE: To investigate the relationship between neuroendocrine differentiation in ovarian mucinous tumors and its genesis. METHODS: A morphologic study of seventy-three cases of ovarian mucinous tumors (32 benign, 20 borderline, 21 malignant) using immunohistochemical and immunohistochemical/histochemical double staining techniques. RESULTS: The study showed that in tumors of benign, borderline and malignant types, the incidence of chromogranin A (CgA) positive cells was 62.5%, 75%, 76% and that of 5-hydroxytryptamine (5-HT) positive cells was 31.3%, 40% and 39%, respectively. Neuroendocrine cells (NEC) were not evenly distributed in any tumor. In four cases of the benign tumors, the number of CgA positive cells was more than 30 percent, localizing between the glandular basement membrane and the mucinous epithelial cells, with many intermediate cells containing both CgA and periodic acid-schiff (PAS) positive granules. CONCLUSION: The occurrence of both neuroendocrine and exocrine granules within the same cell has been previously described as "intermediate" in pancreatic hyperplasia, pancreatic tumors and lung signet-ring cell carcinoids. This has not previously been observed in benign ovarian mucinous tumors. Finding both endocrine and exocrine granules within a single cell seems to indicate a histogenetic relationship between the ovarian endocrine and exocrine cells. The four cases of the benign tumors might be originated from a common stem cell, such as the so-called amphocrine cell. The relationship between these four tumors and neuroendocrine differentiation in ovarian mucinous tumors needs to be further clarified.
UI - 11506467
AU - Tuxen MK; Soletormos G; Petersen PH; Dombernowsky P
TI - Interpretation of sequential measurements of cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) based on analytical imprecision and biological variation in the monitoring of ovarian cancer.
SO - Clin Chem Lab Med 2001 Jun;39(6):531-8
AD - Department of Oncology and Clinical Chemistry, Herlev Hospital, University of Copenhagen, Denmark.
The main objective with cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) monitoring of ovarian cancer patients is to detect an early change of disease activity with high reliability. We hypothesized that a monitoring scheme for ovarian cancer patients with serological tumor markers should take into account the stochastic variation, i.e. the probability that observed increases and decreases may solely be due to analytical imprecision and normal intra-individual biological variation. The aim of this study was to provide a detailed characteristic of the within-subject mean steady state concentrations and the associated variability in healthy individuals with an age distribution representative for ovarian cancer patients. Thirty-one healthy women with a median age of 55 years comprised the study population. Sixteen blood samples were collected from each subject in four series, with four samples per series, over a period of approximately 1 year. We found that, i) natural logarithmic-transformed concentrations were more homogeneously distributed between individuals than the original concentrations, ii) the within-subject mean steady state levels, the standard deviations, and the coefficients of variation differed among subjects, and iii) the steady state variability differed among the markers. In conclusion, our data indicate that the assessment of sequential CA 125, CEA, and TPA concentrations is more complex than hitherto recognized. We suggest that it is necessary to adjust the assessment criteria to the type of marker, and that assessment may be facilitated if based on natural logarithmic transformed concentrations.
UI - 11807777
AU - Buchholz TA; Wu X; Hussain A; Tucker SL; Mills GB; Haffty B; Bergh S;
TI - Story M; Geara FB; Brock WA Evidence of haplotype insufficiency in human cells containing a germline mutation in BRCA1 or BRCA2.
SO - Int J Cancer 2002 Feb 10;97(5):557-61
AD - Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. firstname.lastname@example.org
The BRCA1 and BRCA2 gene products are thought to play important roles in the processing of DNA damage. To assess whether heterozygous mutations in these genes are associated with cellular radiosensitivity, we performed an in vitro radiation clonogenic survival assay on dermal fibroblasts obtained from 8 sequence-proven BRCA heterozygotes (6 BRCA1, 2 BRCA2). These data were compared to results obtained from a previous set of 17 prospectively studied cancer patients who had a negligible risk for a BRCA mutation. In addition, results from radiation-induced chromatid break assay performed on lymphocytes obtained from 9 BRCA heterozygotes (8 BRCA1, 1 BRCA2) were compared to results from a control group of 18 women with no cancer history. Results from both assays suggested that cells containing a heterozygous mutation in BRCA1 or BRCA2 were more radiosensitive than controls. For the fibroblast studies, the mean surviving fraction at 2 Gy (SF2) for carriers was 0.279 vs. 0.348 for the control set (p = 0.007). For the lymphocyte studies, the mean number of chromatid breaks after 125 cGy of radiation was 0.79 breaks per cell for the carriers vs. 0.45 for the controls (p = 0.0005). There was no apparent difference in the radiosensitivity between cells with BRCA1 vs. BRCA2 mutations (p = 0.769), although the small sample size minimizes the certainty of this observation. These preliminary results are consistent with a relationship between a germline mutation in BRCA1 or BRCA2 and a hypersensitivity to radiation. This phenotype could possibly predispose to an increased risk of radiation-induced mutagenesis and carcinogenesis. Copyright 2001 Wiley-Liss, Inc.
UI - 11782386
AU - Shridhar V; Sen A; Chien J; Staub J; Avula R; Kovats S; Lee J; Lillie J;
TI - Smith DI Identification of underexpressed genes in early- and late-stage primary ovarian tumors by suppression subtraction hybridization.
SO - Cancer Res 2002 Jan 1;62(1):262-70
AD - Department of Experimental Pathology, Division of Laboratory Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. email@example.com
To identify novel tumor suppressor genes involved in ovarian carcinogenesis, we generated four down-regulated suppression subtraction cDNA libraries from two early-stage (stage I/II) and two late-stage (stage III) primary ovarian tumors, each subtracted against cDNAs derived from normal ovarian epithelial cell brushings. Approximately 600-700 distinct clones were sequenced from each library. Comparison of down-regulated clones obtained from early- and late-stage tumors revealed genes that were unique to each library which suggested tumor-specific differences. We found 45 down-regulated genes that were common in all four libraries. We also identified several genes, the role of which in tumor development has yet to be elucidated, in addition to several under expressed genes, the potential role of which in carcinogenesis has been described previously (Bagnoli et al., Oncogene, 19: 4754-4763, 2000; Yu et al., Proc. Natl. Acad. Sci. USA, 96: 214-219, 1999; Mok et al., Oncogene, 12: 1895-1901, 1996). The differential expression of a subset of these genes was confirmed by semiquantitative reverse transcription-PCR using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as control in a panel of 15 stage I and 15 stage III tumors of mixed histological subtypes. Chromosomal sorting of library sequences revealed that several of the genes mapped to known regions of deletion in ovarian cancer. Loss of heterozygosity (LOH) analysis revealed multiple genomic regions with a high frequency of loss in both early- and late-stage tumors. To determine whether loss of expression of some of the genes corresponds to loss of an allele by LOH, we used a microsatellite marker for one of the novel genes on 8q and have shown that loss of expression of this novel gene correlates with loss of an allele by LOH. In conclusion, our analysis has identified down-regulated genes, which map to known as well as novel regions of deletions and may represent potential candidate tumor suppressor genes involved in ovarian cancer.
UI - 11826460
AU - Levin T; Reichelt J; Heimdal K; Moller P
TI - [Information to families with hereditary breast and ovarian cancer]
SO - Tidsskr Nor Laegeforen 2001 Nov 20;121(28):3292-4
AD - Seksjon for genetisk veiledning Avdeling for kreftgenetikk Det Norske Radiumhospital 0310 Oslo. firstname.lastname@example.org
BACKGROUND: Under Norwegian legislation, persons at risk should make the initial contact with the proper health personnel, and not vice versa. It may be argued that the physician should be allowed to make contact with persons at risk of preventable or curable disorders. MATERIAL AND METHODS: We identified all first-degree relatives of all 75 BRCA1 mutation carriers diagnosed within a given period of time and asked them whether or not they had been informed by their relatives. RESULTS: After two years, 60/63 (95%) adult sisters and daughters had made contact with us; the remaining three (5%) had been informed. In comparison, 18/45 (40%) adult brothers and sons had contacted us. INTERPRETATION: The legislation constituted no barrier to offering health services to the target group. Information on our services had reached all close relatives who could benefit from them. This may be representative for curable inherited disorders. We examined inherited cancer limited to females; similar studies on inherited cancers in males and on other curable inherited disorders should be performed. Outside the framework of the present study, we are aware of rare examples of distant cousins who have not been properly informed through their families. One legally acceptable way of identifying mutation carrier families is to test all patients with breast or ovarian cancer for causative mutations. Health services should be monitored to make future decisions based on empirical evidence.
UI - 11810077
AU - Walker GR; Schlesselman JJ; Ness RB
TI - Family history of cancer, oral contraceptive use, and ovarian cancer risk.
SO - Am J Obstet Gynecol 2002 Jan;186(1):8-14
AD - Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, Florida, USA.
OBJECTIVE: The purpose of this study was to determine whether women with a family history of ovarian cancer are at reduced risk of ovarian cancer from the use of oral contraceptives and to compare their risk with that of women with no family history of ovarian cancer. STUDY DESIGN: A diagnosis of epithelial ovarian cancer were ascertained from 39 hospitals in 3 northeastern states. Personal interviews with the women and 1367 control subjects provided data that allowed us to estimate the relative risk of ovarian cancer in relation to a family history of cancer and total duration of oral contraception. RESULTS: Among the 33 case patients and 24 control subjects with a first-degree family history of ovarian cancer, risk of ovarian cancer declined with increasing duration of oral contraception (P =.01). Risk reduction from short-term use of oral contraceptives (< or = 48 months) did not differ significantly by family history (combined estimate of odds ratio, 0.72; 90% CI, 0.59%-0.87%). Risk reduction from long-term use of oral contraceptives (>48 months) was greater in women with a positive family history of ovarian cancer (odds ratio, 0.12) than in women with a negative family history of ovarian cancer (odds ratio, 0.51; test of interaction, P =.04; 692 case patients, 1279 control subjects). CONCLUSION: Four to 8 years of oral contraception may substantially reduce the risk of ovarian cancer by age 70 years in women with a family history of the disease, from approximately 4 women per 100 women who did not use oral contraceptives to only 2 women per 100 women who did use oral contraceptives.
UI - 11526704
AU - Rampone B; Rampone A; Tirabasso S; Panariello S; Rampone N
TI - Immunological variations in women suffering from ovarian cancer. Influence of radical surgical treatment.
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):116-9
AD - Institute of Obstetrics and Gynaecology, Second University of Naples, Italy.
BACKGROUND: The immune system includes all the innate or acquired mechanisms, that the organism uses for protecting itself from the aggression of external pathogens or neoplasia. About the control of the tumor growth, the immune mechanisms implicated are quite a lot: the cytotoxicity against the tumor cells by cytotoxic T lymphocyte, macrophages, NK cells; simil-NK cells (ADCC). Tumors have generally antigenic marked potential, for which numerous antigens have been identified, but none of these has revealed a correlated specificity to the neoplasia. Only a glycoprotein at elevated molecular weight, the CA125, presents an elevated specificity and sensibility. The objective of this study was to examine immunological variations in the peripheral blood of patients with ovarian carcinoma before and after radical surgical treatment. METHODS: In the Institute of Obstetrics and Gynaecology of Second University of Studies of Naples the immunological variations in 8 women (mean age: 59.5; range: 49-70 years) suffering from ovarian cancer, have been evaluated before and after radical surgical treatment (when the stage of the tumor made possible the surgery) and compared to 8 normal volunteers of comparable age (control in average for two years and subjected to a immunological screening with blood drawings effected at the hospitalisation and later 1, 6, 12, 18, 24 months from surgical treatment. The immune evaluation were effected with: proliferation tests on the monocytes of the peripheral blood, evaluation of the production of Interleukin 1 and 2 with the leukocyte phenotyping, evaluation of NK cells activity. The patients were followed in average for two years. RESULTS: The radical surgery decidedly improves the immune response. The ability to produce IL-1 by the lymphocytes of the patients object of our study, appeared constantly falling (with reduction of about 50%) before the surgery and it meaningfully increases in the post-surgery period. The surgery doesn't modify the lymphocytes T helper and T inducer. The surgery delays the diminution of the NK cells in a little meaningful way. The periodic dosage of the CA125 does not give the same results: in the 60% a progressive increase was realised and in the 40% it remained constant. CONCLUSIONS: The surgery constantly improved the physical state of the patient, determining an increase of the immune response toward the neoplasia, and therefore achieving a meaningful increase of survival.
UI - 11526705
AU - Catizone FA; Gesmundo G; Catizone C; Sena T; Mastrantonio P
TI - [Limitations and expectations of Doppler color in the diagnosis of ovarian cancer]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):12-7
AD - Istituto di Scienze Ginecologiche e Pediatriche, Universita Magna Grecia, Catanzaro.
UI - 11526707
AU - Rampone B; Rampone A; Tirabasso S; Panariello S; Rampone N
TI - Ovarian cancer screening by transvaginal color Doppler ultrasonography.
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):125-8
AD - Institute of Obstetrics and Gynaecology, Second University of Naples, Italy.
BACKGROUND: The need for the early detection of ovarian cancer continues to be one of the most important issue in women's health care. The ovarian neoplasia characteristically have a scarce symptomatology for which it tries to create a sensitive and specific screening test so that the diagnosis could precociously be made and, consequently, improve the prognosis with a timely therapy. Our purpose was to assess the performance of transvaginal color Doppler ultrasonography in ovarian cancer screening. METHODS: In the Institute of Obstetrics and Gynaecology of Second University of Studies of Naples, in the period groups (the 1st group included 30 women in fertile age with standard uterine dimensions, the 2nd group included 30 menopausal women), were submitted to transvaginal color Doppler ultrasonography. Color Doppler ultrasonography was performed with an ESAOTE ANSALDO AU5 HARMONIC ultrasound machine provided with a 6.5 MHz real-time sector electronic array endovaginal probe with a 5 MHz pulsed Doppler system and equipped with the color velocity imaging system for the color blood flow codification. The score used in the evaluation of the ovary are us follows: volume of the adnexa (from 1 to 5); presence of papillas and septa (from 1 to 5); wall thickness (from 1 to 5). An high score (> 12) corresponds to probability of presence of neoplasia. For the flow modifications the following parameters were considered: RI (Index of resistance); PI (Pulse Index); Vmax (Maximum Speed). CD was considered as suspicious when flow was detected and the lowest RI found was < or = 0.45, PI < or = 0.58 Vmax < or = 60. RESULTS: Sonographic morphology evaluation and CD were suspicious in 11 cases and 9 of these were positive on histopathological analysis (true positive = 15%, false positive = 5%). All the women that had morphologically normal ovaries observed on ultrasound examination and were not suspicious on CD analysis, were also negative on histopathological analysis (true negative = 80%). CONCLUSIONS: The color Doppler ultrasonography revealed a decidedly valid method of screening of the first level, being non-invasive examination, painless, therefore well accepted by the patients, even if in some women, especially if in fertile age, the physiological modifications calls for repeated investigations and compare its parameters.
UI - 11526715
AU - Greggi S; Legge F; Mancuso S
TI - [Familial ovarian carcinoma]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):3-5
AD - Istituto di Clinica Ostetrica e Ginecologica, Universita Cattolica del Sacro Cuore, Roma.
UI - 11526717
AU - Amunni G; Susini T; Villanucci A; Massi GB
TI - [Recurrence of malignant epithelial tumors of the ovary]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):37-9
AD - I Clinica Ginecologica e Ostetrica, Universita degli Studi, Firenze.
UI - 11526718
AU - Ferrandina G; Legge F; Fagotti A; Fanfani F; Mancuso S; Scambia G
TI - [Biological factors with prognostic significance in ovarian cancer]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):40-5
AD - Istituto di Clinica Ostetrica e Ginecologica, Universita Cattolica del Sacro Cuore, Roma.
UI - 11526719
AU - Imparato E; Parodi M
TI - [Treatment of intestinal and urinary tract obstruction in patients with advanced ovarian disease]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):46-7
AD - Divisione di Ginecologia e Ostetricia, E.O. Ospedali Galliera, Genova.
UI - 11526723
AU - Bolis PF; Zanaboni F; Crotti S
TI - [Borderline ovarian tumors]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):6-9
AD - Clinica Ostetrica e Ginecologica, Universita dell'Insubria, Sede vi Varese.
UI - 11526726
AU - Saponara R; Menditto A; Russo G; Musone R; Balbi GC; Balbi C
TI - [Review of the literature on BRCA 1 and BRCA 2]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):72-4
AD - Istituto di Clinica Ostetrica e Ginecologica, Seconda Universita degli Studi, Napoli.
UI - 11526732
AU - Iervolino P; Palmieri M; Rotondi M; D'Alessandro P; Iuliano R
TI - [Borderline ovarian tumors. Retrospective analysis of 20 cases]
SO - Minerva Ginecol 2001 Feb;53(1 Suppl 1):97-9
AD - Divisione di Ostetricia e Ginecologia, Ospedale S. Maria di Loreto Nuovo, Napoli.
BACKGROUND: To evaluate the clinical features, the surgical management and outcome of 20 patients with stage-I borderline ovarian tumors. METHODS: Twenty cases of FIGO stage-I ovarian tumors, aged from 31 to 58 years (mean 37 years) have been reviewed. All informations of clinical stage, surgical intervention and prognosis were achieved by reviewing hospital records. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour. RESULTS: Eleven of the 20 patients (55%) were at stage IA, 6 cases (30%) were at stage IB, 3 cases (15%) were at stage IC. Thirteen (65%) were with mucinous cystadenoma of borderline malignancy, 7 cases (35%) were of serous type. Thirteen patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO). Seven patients were treated with unilateral oophorectomy or unilateral salpingo-oophorectomy (USO). One patient underwent enucleation of ovarian tumor and biopsy of contralateral ovary. Any patient were treated with chemotherapy after operation. With a median follow up of two years, we observed no recurrence of carcinoma in women treated conservatively or in those treated more radically. CONCLUSIONS: Conservative surgery remains a therapeutic option in selected patients with borderline ovarian tumors. Prolonged intensive follow-up is required for women treated conservatively for borderline malignant ovarian tumours.
UI - 11714114
AU - Purdie DM; Bain CJ; Webb PM; Whiteman DC; Pirozzo S; Green AC
TI - Body size and ovarian cancer: case-control study and systematic review (Australia).
SO - Cancer Causes Control 2001 Nov;12(9):855-63
AD - Queensland Institute of Medical Research, Herston, Australia. davidP@qimr.edu.au
OBJECTIVE: Although increased body mass is an established risk factor for a variety of cancers, its relation with cancer of the ovary is unclear. We therefore investigated the association between measures of body mass index (BMI) and ovarian cancer risk. METHODS: Data from an Australian case-control study of 775 ovarian cancer cases and 846 controls were used to examine the association with BMI. We have also summarized the results from a number of other studies that have examined this association. RESULTS: There was a significant increased risk of ovarian cancer with increasing BMI, with women in the top 15% of the BMI range having an odds ratio (OR) of 1.9 (95% confidence interval (CI), 1.3-2.6) compared with those in the middle 30%. Stratifying by physical activity showed a stronger effect among inactive women (OR = 3.0, 95% CI 1.3-6.9). The overall effect was consistent with the findings of most prior population-based case-control studies, while cohort studies reported positive effects closer to the null. Hospital-based studies gave variable results. CONCLUSIONS: Taken together, the evidence is in favor of a small to moderate positive relation between high BMI and occurrence of ovarian cancer.
UI - 11780319
AU - Ye D; Xie X; Lu W; Chen H; Cheng B
TI - Growth inhibition of interleukin-2 receptor gene-transduced peripheral blood lymphocytes on human ovarian cancer cells.
SO - Chin Med J (Engl) 2001 Mar;114(3):303-7
AD - Department of Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
OBJECTIVE: To investigate the growth inhibition of interleukin-2 receptor (IL-2R) gene-transduced peripheral blood lymphocytes (PBLs) on human ovarian cancer cells. METHODS: Interleukin-2 (IL-2) and IL-2R genes were transfected into human ovarian cancer cell line 3AO and PBLs, respectively, using the same Fugene vector. Twenty-four hours later transfected and nontransfected PBLs were cocultured with transfected and nontransfected 3AO for 48 hours. cytotoxicity of PBLs on 3AO was detected by the MTT assay. RESULTS: The morphology of IL-2-transduced 3AO and IL-2R-transduced PBLs remained unchanged. 3AO cells could be transfected with the IL-2 gene and expressed IL-2 mRNA, and PBLs could be transfected with the IL-2R gene and expressed IL-2R mRNA. IL-2 transduced 3AO cells enhanced their response to the cytotoxicity of PBLs. Furthermore, growth inhibition of PBLs to 3AO cells increased significantly when the IL-2R was transfected into PBLs and when the IL-2 gene was transfected into 3AO cells and the two were combined. CONCLUSIONS: IL-2R gene transduced PBLs are able to enhance their cytotoxicity on IL-2 gene transduced ovarian cancer cells. This method may be a new way to investigate IL-2 gene therapy for ovarian cancer.
UI - 11780192
AU - Wei F; Jiang Z; Yan C
TI - Analysis of 20 mature ovarian cystic teratoma cases in postmenopausal women.
SO - Chin Med J (Engl) 2001 Feb;114(2):137-8
AD - Department of Obstetrics and Gynecology, Beijing Hospital, Beijing 100730, China. email@example.com
OBJECTIVE: To study the incidence of malignant change, diagnosis and management of mature cystic teratomas in postmenopausal women. METHODS: Twenty cases of mature cystic teratoma in postmenopausal women admitted retrospectively reviewed and evaluated. RESULTS: The number of postmenopausal patients with mature cystic teratoma (20) accounted for 7.6% of the total number of patients with benign ovarian teratomas (263). There were 3 cases of malignant change, which were squamous carcinoma, carcinosarcoma, and digestive gland epithelial carcinoma. The incidence of malignant change was 15%. CONCLUSION: In postmenopausal women, mature ovarian cystic teratoma should be treated as lowly malignant and should be paid much attention.
UI - 11779836
AU - Manderson EN; Mes-Masson AM; Novak J; Lee PD; Provencher D; Hudson TJ;
TI - Tonin PN Expression profiles of 290 ESTs mapped to chromosome 3 in human epithelial ovarian cancer cell lines using DNA expression oligonucleotide microarrays.
SO - Genome Res 2002 Jan;12(1):112-21
AD - Department of Human Genetics, McGill University, Montreal, Quebec H3A 1B1, Canada.
We have investigated previously the utility of oligonucleotide expression microarray technology in an analysis of four spontaneously transformed epithelial ovarian cancer (EOC) cell lines, TOV-21G, TOV-81D, OV-90, and TOV-112D. Here, we examine the expression of 290 expressed sequence tags (ESTs) that map to human chromosome 3 in a primary culture derived from normal ovarian surface epithelium (NOSE), NOV-31, and the four spontaneously transformed EOC cell lines. One of these cell lines, OV-90, harbors a deletion of an entire chromosome 3p arm. Whereas the most aggressive cell lines (OV-90, TOV-112D, and TOV-21G) exhibited the highest levels of expression, assessed by the mean of expression values of all ESTs, OV-90 showed the lowest mean of expression of ESTs that map to the 3p arm in comparison with TOV-112D and TOV-21G. This difference in expression profile of 3p ESTs in OV-90 is also reflected in the ratio of expression of ESTs on 3p versus the 3q arm and in that the expression values of ESTs that map to 3p were more often lower than higher in OV-90 in two-way comparisons with NOV-31, TOV-21G, and TOV-112D