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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Ovarian Cancer - August 2002
National Cancer Institute®
Last Modified: August 1, 2002
- BRCA1 and BRCA2 mutations in Turkish familial and non-familial ovarian cancer patients: a high incidence of mutations in non-familial cases.
- Predicting response of ovarian cancer to paclitaxel treatment based on trend analysis of serum CA125.
- Expression of MUC1 splice variants in benign and malignant ovarian tumours.
- BRCA2 mutation analysis of 87 Spanish breast/ovarian cancer families.
- What do we expect from imaging?
- Staging ovarian cancer: role of imaging.
- Usefulness of FDG PET for assessment of early recurrent epithelial ovarian cancer.
- Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor
- Analysis of chemokines and chemokine receptor expression in ovarian cancer ascites.
- The Department of Defense Congressionally Directed Medical Research Program: innovations in the federal funding of biomedical research.
- The search for predictive patterns in ovarian cancer: proteomics meets bioinformatics.
- Novel target antigens for dendritic cell-based immunotherapy against ovarian cancer.
- Transcriptional profiling reveals that several common fragile-site genes are downregulated in ovarian cancer.
- Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic ovarian cancer.
- Common polymorphisms and somatic mutations in human base excision repair genes in ovarian and endometrial cancers.
- Is well-differentiated endometrioid carcinoma of the ovary indeed an invasive carcinoma?
- Immunohistochemical evaluation of a new epithelial antigen, Ber-EP4, in ovarian cancer: preliminary results.
- [Treatment of ovarian cancer]
- Cigarette smoking and the risk of mucinous and nonmucinous epithelial ovarian cancer.
- Clustering of cancer-related mutations in a subset of BRCA1 alleles: a study in the Spanish population.
- Identification of the primary site of metastatic adenocarcinoma in serous effusions. Value of an immunocytochemical panel added to the
- FDG positron emission tomography for the detection of ovarian cancer.
- Proteomic patterns in serum and identification of ovarian cancer.
- Ovarian carcinoma and serous effusions. Changing views regarding tumor progression and review of current literature.
- BRCA mutations in Italian breast/ovarian cancer families.
- [Peritoneal glioblastoma: recurrence of ovarian immature teratoma (report of a case)]
- Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma.
- CYP1A1 gene polymorphism and risk of epithelial ovarian neoplasm.
- Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer.
- Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer.
- Treatment preferences in recurrent ovarian cancer.
- Psychological impact of prophylactic oophorectomy in women at increased risk of developing ovarian cancer: a prospective study.
- Low proliferation activity may be associated with chemoresistance in clear cell carcinoma of the ovary.
- Obesity, weight gain, and ovarian cancer.
- Transitional cell ovarian carcinoma in a BRCA1 mutation carrier.
- Expression of angiopoietin-1, angiopoietin-2, and Tie2 genes in normal ovary with corpus luteum and in ovarian cancer.
- Hormone replacement therapy and the risk of ovarian cancer.
- Genetic alterations in epithelial ovarian tumors analyzed by comparative genomic hybridization.
- Risk factors for invasive epithelial ovarian cancer: results from a Swedish case-control study.
- Risk of epithelial ovarian cancer in relation to use of antidepressants, benzodiazepines, and other centrally acting medications.
- Effects of genetic consultation on perception of a family risk of breast/ovarian cancer and determinants of inaccurate perception after
- A BRCA1 mutation in Native North American families.
- Adherence to repeat screening flexible sigmoidoscopy in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
- The ovarian tumor index predicts risk for malignancy.
Table of Contents
1
UI - 12112655
AU - Yazici H; Glendon G; Yazici H; Burnie SJ; Saip P; Buyru F; Bengisu E;
TI -
Andrulis IL; Dalay N; Ozcelik H
BRCA1 and BRCA2 mutations in Turkish familial and non-familial ovarian
cancer patients: a high incidence of mutations in non-familial cases.
SO - Hum Mutat 2002 Jul;20(1):28-34
AD - Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, and
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital,
Toronto, Canada.
Ovarian cancer is a clinically important cancer in Turkey. The
contribution of BRCA1 and BRCA2 to ovarian cancer in Turkish patients
has not previously been described. In this study we investigated the
presence of BRCA1 and BRCA2 mutations in 102 consecutively ascertained,
hospital-based, ovarian cancer cases. Four out of 15 (26.7%, 95%
confidence interval (CI), 7.8%-55.1%) familial cases were found to carry
mutations in BRCA1. Thirteen of the 87 (14.9%, 95% CI, 7.5%-22.4%)
non-familial cases had BRCA1 and BRCA2 mutations, six in BRCA1, and
seven in BRCA2. We have further studied the non-familial ovarian cancer
cases to determine which subgroups have a likelihood of carrying
clinically important mutations. Our study shows that those Turkish
ovarian cancer patients with serous histopathology harbor a high
proportion of mutations (12/58, 20.7%, 95% CI, 10.3%-31.1%) compared to
all non-familial cases (14.9%) regardless of pathology. Within the
serous sub-group, those that were also diagnosed below age 50 have an
even greater percentage of mutations (8/28, 28.6%, 95% CI, 11.8%-45.3%).
Our findings demonstrate that a substantial proportion of Turkish
ovarian cancer patients, both with and without a family history, carry
BRCA1 and BRCA2 mutations, demonstrating the importance of BRCA1 and
BRCA2 in the development of ovarian cancer in this population. Copyright
2002 Wiley-Liss, Inc.
2
UI - 12142397
AU - Nekulova M; Pecen L; Kalabova R; Simickova M; Topolcan O; Pikner R;
TI -
Vondracek V; Valik D
Predicting response of ovarian cancer to paclitaxel treatment based on
trend analysis of serum CA125.
SO - Clin Chem 2002 Aug;48(8):1364-7
AD - Department of Laboratory Medicine, Masaryk Memorial Cancer Institute,
Zluty kopec 7, 656 65 Brno, The Czech Republic.
3
UI - 12115565
AU - Obermair A; Schmid BC; Packer LM; Leodolter S; Birner P; Ward BG;
TI -
Crandon AJ; McGuckin MA; Zeillinger R
Expression of MUC1 splice variants in benign and malignant ovarian
tumours.
SO - Int J Cancer 2002 Jul 10;100(2):166-71
AD - Queensland Centre for Gynaecological Cancer, Royal Brisbane Hospital,
Brisbane, Australia. a_obermair@hotmail.com
MUC1 is expressed on the surface of ovarian cancer cells. Nine different
splice variants of MUC1 have been described, but no study has reported
on the expression of MUC1 isoforms in human ovarian cancer. Our study
compares patterns of expression of MUC1 splice variants of malignant and
benign ovarian tumours. Ovarian tissue samples were taken from patients
with benign ovarian tumours (n = 34) and from patients who had surgery
for primary (n = 47) or recurrent (n = 8) ovarian cancer. RT-PCR for
MUC1 splice variants A, B, C, D, X, Y, Z, REP and SEC was performed and
their expression compared to clinical and histopathologic parameters.
Variants A, D, X, Y and Z were more frequently expressed in malignant
than in benign tumours. All primary ovarian cancer cases were positive
for variant REP but negative for variant SEC. No significant association
of the expression of MUC1 splice variants with the response to
chemotherapy or patient survival could be demonstrated. Expression of
MUC1 splice variants A, D, X, Y, Z and REP is associated with the
presence of malignancy, whereas expression of MUC1/SEC is associated
with the absence of malignancy. Copyright 2002 Wiley-Liss, Inc.
4
UI - 11843247
AU - Campos B; Diez O; Domenech M; Baena M; Pericay C; Balmana J; del Rio E;
TI -
Sanz J; Alonso C; Baiget M
BRCA2 mutation analysis of 87 Spanish breast/ovarian cancer families.
SO - Ann Oncol 2001 Dec;12(12):1699-703
AD - Servei de Genetica, Hospital de la Santa Creu i Sant Pau, Barcelona,
Spain.
BACKGROUND: It is estimated that about 5% -10% of breast cancer (BC)
cases is due to inherited predisposition. Early works reported that
45%-50% of site-specific BC families had BRCA1 mutations and 25%-35%
BRCA2 mutations. However, these percentages could have been
overestimated and likely vary among the populations studied. PATIENTS
AND METHODS: We analysed the BRCA2 gene in 87 Spanish breast/ovarian
cancer families in which the BRCA1 mutation screening was negative.
RESULTS: We detected 15 (17.2%) disease-causing mutations and 11
polymorphisms and unclassified variants. Four mutations were recurrent,
and five were novel. Seven (47%) mutations were found in site-specific
female BC families, five (33%) in families with OC cases, and three
(20%) mutations in families with male BC cases. There was incomplete
penetrance of the mutations in some families, and considerable
phenotypic variations with respect to the age of diagnosis and cancer
types. CONCLUSIONS: The percentage of mutations detected reinforces the
possibility that some of these families have mutations in genes other
than BRCA1 or BRCA2 that confer lower BC risks.
5
UI - 12117191
AU - Barakat RR; Hricak H
TI -
What do we expect from imaging?
SO - Radiol Clin North Am 2002 May;40(3):521-6, vii
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York,
NY 10021, USA. barakatr@mskcc.org
The objectives of imaging in gynecologic cancer include tumor detection,
tumor diagnosis, staging, and follow-up. In addition, both monitoring
response to treatment and differentiating tumor recurrence from
post-treatment changes are important indications for imaging. In 2001 it
was estimated that there would be 38,300 cases of endometrial cancer,
23,400 cases of ovarian cancer, and 12,900 cases of cervical cancer.
This article reviews what information is required by the practicing
gynecologist or gynecologic oncologist prior to surgery and briefly
summarizes state-of-the-art imaging in answering clinically pertinent
questions.
6
UI - 12117196
AU - Coakley FV
TI -
Staging ovarian cancer: role of imaging.
SO - Radiol Clin North Am 2002 May;40(3):609-36
AD - Department of Radiology, University of California San Francisco, 94143,
USA. Fergus.Coakley@radiology.ucsf.edu
Ovarian cancer is relatively common, and often presents at an advanced
stage with widespread intraperitoneal metastases. The constellation of
complex pelvic masses, ascites, omental cake, and other peritoneal
implants is virtually diagnostic. All patients are potential surgical
candidates, since suspected early stage disease is treated by a
comprehensive staging laparotomy including total abdominal hysterectomy,
bilateral salpingo-oophorectomy, and omentectomy. Operable advanced
disease is treated by surgical debulking and adjuvant combination
chemotherapy. The role of imaging is to detect and characterize adnexal
masses as likely malignant, recognize unusual findings that may suggest
atypical pathology, demonstrate metastases in order to prevent
under-staging, and detect specific sites of disease that may be
unresectable. These aims are directly related to clinical management;
characterization of an adnexal mass as malignant guides appropriate
surgical referral, recognition of atypical pathology such as malignant
granulosa cell tumor in a young woman may be an indication for
fertility-preserving surgery. Demonstration of metastatic site-assists
surgical planning, and detection of unresectable disease may be an
indication for neoadjuvant (ie, preoperative) chemotherapy with interval
debulking rather than primary debulking with adjuvan (postoperative)
chemotherapy.
7
UI - 12130439
AU - Cho SM; Ha HK; Byun JY; Lee JM; Kim CJ; Nam-Koong SE; Lee JM
TI -
Usefulness of FDG PET for assessment of early recurrent epithelial
ovarian cancer.
SO - AJR Am J Roentgenol 2002 Aug;179(2):391-5
AD - Department of Radiology, College of Medicine, The Catholic University of
Korea, Seocho-Ku, Seoul, South Korea.
OBJECTIVE: The purpose of our study was to evaluate the diagnostic
accuracy of FDG positron emission tomography (PET) in comparison with CT
in detecting recurrent ovarian carcinoma and its ability to reveal small
tumor recurrence. MATERIALS AND METHODS: We reviewed the records of 31
consecutive patients with pathologically proven epithelial carcinoma who
underwent FDG PET 1 month before second-look surgery to assess recurrent
tumor. Of these 31 patients, 21 patients also underwent CT 1 month
before second-look surgery. The diagnostic accuracies of FDG PET (n =
31), CT (n = 21), and combined FDG PET and CT (n = 21) in detecting
recurrent tumor were calculated and compared with each other using the
Bennett's test in 21 patients who underwent both imaging studies.
Detection rates of individual tumors relative to their sizes were
compared between FDG PET and CT using the McNemar test. RESULTS: The
sensitivity, specificity, and accuracy of FDG PET, CT, and combined FDG
PET and CT for revealing recurrent ovarian cancer were 45.3%, 99.7%,
91.0%; 54.5%, 99.6%, 91.7%; 58.2%, 99.6%, 92.4%, respectively. We found
no statistically significant difference in the diagnostic accuracy of
FDG PET, CT, and combined FDG PET and CT (chi(2) < 5.991). Detection
rates of tumor nodules found on CT were significantly greater than those
on FDG PET when nodule size was 0.3-0.7 cm (p < 0.05). CONCLUSION: FDG
PET did not improve the overall diagnostic accuracy in detecting
recurrent ovarian carcinoma compared with CT. Rather, FDG PET was
inferior to CT in its ability to reveal small-tumor recurrence.
8
UI - 11948120
AU - Oberst MD; Johnson MD; Dickson RB; Lin CY; Singh B; Stewart M; Williams
TI -
A; al-Nafussi A; Smyth JF; Gabra H; Sellar GC
Expression of the serine protease matriptase and its inhibitor HAI-1 in
epithelial ovarian cancer: correlation with clinical outcome and tumor
clinicopathological parameters.
SO - Clin Cancer Res 2002 Apr;8(4):1101-7
AD - Department of Oncology, Lombardi Cancer Center, Georgetown University
Medical Center, Washington, DC 20007, USA.
PURPOSE: Matriptase is a type II transmembrane serine protease expressed
by cells of surface epithelial origin, including epithelial ovarian
tumor cells. Matriptase cleaves and activates proteins implicated in the
progression of ovarian cancer and represents a potential prognostic and
therapeutic target. The aim of this study was to examine the expression
of matriptase, and its inhibitor, hepatocyte growth factor activator
inhibitor-1 (HAI-1), in epithelial ovarian cancer and to assign
clinicopathological correlations. EXPERIMENTAL DESIGN: We have
determined by immunohistochemistry the expression of matriptase and
HAI-1 in 54 epithelial ovarian cancers. Statistical analyses of
immunohistochemistry expression data with clinical outcome and
clinicopathological parameters were then performed. RESULTS: Of 54
tumors tested, 39 (72%) and 11 (20%) were positive for matriptase and
for HAI-1, respectively. All HAI-1-positive tumors were also matriptase
positive. Analysis of clinicopathological parameters demonstrated a loss
of matriptase associated with stage III/IV tumors as compared with stage
I/II tumors (P = 0.030). There was also a loss of HAI-1 expression
associated with stage III/IV tumors (P = 0.039). Of 34 stage I/II
tumors, 28 (82%) stained positive for matriptase, and 10 (29%) stained
positive for HAI-1; 10 (29%) tumors showed coexpression. Of 20 stage
III/IV tumors, however, 11 stained positive for matriptase (55%), only 1
of which coexpressed HAI-1 (P = 0.039). CONCLUSIONS: Advanced-stage
ovarian tumors that express matriptase are more likely to do so in the
absence of its inhibitor, HAI-1, indicating that an imbalance in the
matriptase:HAI-1 ratio could be important in the development of advanced
disease. Such an imbalance could promote the proteolytic activity of
matriptase and, consequently, a more invasive phenotype.
9
UI - 11948121
AU - Milliken D; Scotton C; Raju S; Balkwill F; Wilson J
TI -
Analysis of chemokines and chemokine receptor expression in ovarian
cancer ascites.
SO - Clin Cancer Res 2002 Apr;8(4):1108-14
AD - Cancer Research UK Translational Oncology Laboratory, St. Bartholomew's
and the London, Queen Mary's School of Medicine and Dentistry, John Vane
Science Centre London, United Kingdom.
PURPOSE: Ascitic disease is a common occurrence in human ovarian cancer,
but it is unclear how the cellular composition of ascitic fluid is
determined. Because chemokines can determine host cell infiltration in
solid ovarian cancer, we assessed CC chemokine protein and CC chemokine
receptor expression in ovarian cancer ascites. EXPERIMENTAL DESIGN: We
used reverse transcription-PCR and RNase protection assay to determine
CC chemokine and chemokine receptor mRNA expression and ELISA to measure
CC chemokine protein levels. Flow cytometry was used to identify cell
populations and their chemokine receptor protein expression. RESULTS:
mRNA for the CC chemokines CCL2, -3, -4, -5, -8, and -22 was expressed
in cell isolates from ascites samples, and the corresponding proteins
were detected in ascitic fluid. mRNA for CC chemokine receptors CCR1,
-2a, -2b, -3, -4, -5, and -8 was detected in cells from ascites.
Fluorescence-activated cell-sorting analysis showed variable numbers of
macrophages and CD3(+) T lymphocytes (predominantly CD4(+)) within
ovarian cancer ascites. CD14(+) macrophages within ascites consistently
expressed protein for CCR1, -2, and -5. CCR1 was expressed by >60% of
all T cells, but more CD4(+) than CD8(+) T cells expressed CCR2 and -5.
A direct correlation was found between the CCL5 concentration and CD3(+)
T-cell infiltration. CONCLUSIONS: We conclude that there is a complex
chemokine/chemokine receptor network in ovarian cancer ascites. However,
associations between chemokine receptor expression, chemokine levels,
and cell counts were limited.
10
UI - 11948100
AU - Young-McCaughan S; Rich IM; Lindsay GC; Bertram KA
TI -
The Department of Defense Congressionally Directed Medical Research
Program: innovations in the federal funding of biomedical research.
SO - Clin Cancer Res 2002 Apr;8(4):957-62
AD - United States Army Medical Research and Materiel Command,
Congressionally Directed Medical Research Programs, Fort Detrick,
Maryland 21702-5024, USA.
In response to the lobbying efforts of the women's advocacy movement, in
1993 Congress authorized funds for a substantial increase in support of
new and promising research aimed at the eradication of breast cancer.
This appropriation resulted in a major expansion of the United States
Army Medical Research and Materiel Command, Department of Defense Breast
Cancer Research Program. The Office of Congressionally Directed Medical
Research Programs was established within the United States Army Medical
Research and Materiel Command to facilitate the management of the
expanded extramural research program. Since that time, the programs have
grown to include not just breast cancer but also prostate cancer,
ovarian cancer, and neurofibromatosis. The unique appropriations to the
Office of Congressionally Directed Medical Research Programs has
resulted in a number of programmatic innovations. These include
development of unique mechanisms of grant support, inclusion of consumer
advocates on peer and programmatic review panels, and the introduction
of criteria-based evaluation and scoring in peer review. This article
describes these novel scientific management strategies and outlines
their success in meeting program visions and goals.
11
UI - 12086867
AU - Daly MB; Ozols RF
TI -
The search for predictive patterns in ovarian cancer: proteomics meets
bioinformatics.
SO - Cancer Cell 2002 Mar;1(2):111-2
AD - Division of Population Science, Fox Chase Cancer Center, 7701 Burholme
Avenue, Philadelphia, PA 19111, USA. mb_daly@fccc.edu
Proteomic patterns in serum that discriminate between malignant and
benign ovaries may provide a powerful tool for screening in high risk
women.
12
UI - 12113075
AU - Cannon MJ; O'Brien TJ; Underwood LJ; Crew MD; Bondurant KL; Santin AD
TI -
Novel target antigens for dendritic cell-based immunotherapy against
ovarian cancer.
SO - Expert Rev Anticancer Ther 2002 Feb;2(1):97-105
AD - Department of Obstetrics and Gynecology, University of Arkansas for
Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.
cannonmartin@uams.edu
Identification of tumor-specific target antigens has been a major hurdle
for the treatment of malignant disease by vaccination or immunotherapy.
A second challenge has been the induction of therapeutically effective
immune responses to these 'self' antigens. The recent recognition of
dendritic cells as powerful antigen-presenting cells capable of inducing
primary T-cell responses in vitro and in vivo--in combination with
identification of tumor-specific antigens--has generated widespread
interest in dendritic cell-based immunotherapy against a wide variety of
tumors. In this review, a series of recently identified novel ovarian
tumor antigens is discussed, and the potential for therapeutic dendritic
cell vaccination targeted against these antigens is assessed.
13
UI - 12112530
AU - Denison SR; Becker NA; Ferber MJ; Phillips LA; Kalli KR; Lee J; Lillie
TI -
J; Smith DI; Shridhar V
Transcriptional profiling reveals that several common fragile-site genes
are downregulated in ovarian cancer.
SO - Genes Chromosomes Cancer 2002 Aug;34(4):406-15
AD - Division of Experimental Pathology, Department of Laboratory Medicine
and Pathology, Mayo Foundation, 200 First Street SW, Rochester, MN
55905, USA.
Previous transcriptional profiling analysis of 14 primary ovarian tumors
identified approximately 12,000 genes as decreased in expression by at
least twofold in one or more of the tumors sampled. Among those genes
were several known to be mapped to common fragile sites (CFSs), some of
which had previously been shown to exhibit a loss of expression in
ovarian carcinoma. Therefore, we selected a subset of genes to determine
whether they localized within CFSs. Of the 262 genes that were
downregulated at least twofold in 13 of 14 tumors, 10 genes were
selected based on the following criteria: localization to a CFS band;
documented aberrations in at least one malignancy; and feasibility of
scoring breakage at the specific CFS. Fluorescence in situ hybridization
analysis was performed using bacterial artificial chromosome clones
encompassing portions of the genes to determine the position of the
genes relative to their corresponding CFSs. Nine genes were determined
to localize within seven previously uncloned CFSs. Semiquantitative
reverse-transcription/polymerase chain reaction analysis of the cell
lines and primary ovarian tumors validated the downregulation of seven
of the 10 genes. We identified portions of seven uncloned CFSs and
provide data to suggest that several of the genes mapping within CFSs
may be inactivated in ovarian cancer. Copyright 2002 Wiley-Liss, Inc.
14
UI - 12124354
AU - Chan KY; Ozcelik H; Cheung AN; Ngan HY; Khoo US
TI -
Epigenetic factors controlling the BRCA1 and BRCA2 genes in sporadic
ovarian cancer.
SO - Cancer Res 2002 Jul 15;62(14):4151-6
AD - Department of Pathology, Queen Mary Hospital and the University of Hong
Kong, Hong Kong.
Hypermethylation of the BRCA1 promoter has previously been shown to
cause reduced mRNA expression in both breast and ovarian cancers.
Nothing is yet known of the expression pattern or methylation status of
the promoter region of BRCA2 in sporadic ovarian cancer. Whereas our
analysis of 30 sporadic ovarian carcinomas showed a statistically
significant reduction of BRCA1 mRNA expression (P = 0.001), it also
showed, in contrast, overexpression of BRCA2 mRNA (P = 0.002) in tumor
compared with nontumor. Hypermethylation of the BRCA1 promoter highly
correlated with decreased BRCA1 expression (P = 0.017). Methylated CpGs
at the BRCA2 promoter were either absent or at very low levels in tumor
DNA, whereas they were present at high levels in nontumor DNA. Such
hypomethylation also correlated with elevated levels of BRCA2 mRNA (P =
0.043) and showed a statistically significant correlation with tumor
stage (P = 0.037). This supports the role of methylation in BRCA2
contributing to the pathogenesis of sporadic ovarian cancer.
Furthermore, 14 (58.2%) and 9 (56.3%) of all of the cases with aberrant
BRCA mRNA expression and methylation patterns, respectively,
demonstrated opposing mRNA expression and methylation patterns of the
BRCA1 and BRCA2 genes within the same cases. Our findings suggest that
both genes may be involved in the development of sporadic ovarian
cancer.
15
UI - 11465542
AU - Pieretti M; Khattar NH; Smith SA
TI -
Common polymorphisms and somatic mutations in human base excision repair
genes in ovarian and endometrial cancers.
SO - Mutat Res 2001 Jan;432(3-4):53-9
AD - Department of Pathology, University of Kentucky, Lexington 40536, USA.
mpieretti@usamail.usouthal.edu
The purpose of this study was to determine whether the human APEX and
OGG1 genes, encoding proteins important in base excision repair (BER) of
DNA, contain nucleotide sequence polymorphisms or are mutated
somatically in tumors from women diagnosed with ovarian or endometrial
cancer. Based upon the analysis of germline DNA from 83 individuals, 63
with ovarian cancer and 20 with endometrial cancer, we found two
missense polymorphisms in APEX (Q51H and D 148E) and two missense (A3P
and S326C) and one intronic (Exon 5-15 bp) polymorphism in OGG1. The
frequencies of the various alleles (in the ovarian and endometrial
cancer patients combined) were 4.8% for 51-His and 56.2% for 148-Glu in
APEX, and 1.0% for 3-Pro and 20.0% for 326-Cys in OGG1. Somatic
mutations in APEX (P112L, W188X and R237C) were identified in three of
20 endometrial tumors, but no mutations were identified in APEX in 43
ovarian tumors, or in OGG1 at either tumor site. Given the crucial role
of the APEX and OGG1 proteins in BER of oxidative DNA damage, the
identified polymorphisms are good candidates for genetic epidemiologic
studies of cancer susceptibility, while the finding that three of 20
(15%) endometrial tumors have somatic mutations in APEX suggests that
inactivation of the BER pathway is important for the development of
endometrial cancer in at least a subset of cases.
16
UI - 11688473
AU - Zamecnik M
TI -
Is well-differentiated endometrioid carcinoma of the ovary indeed an
invasive carcinoma?
SO - Am J Surg Pathol 2001 Oct;25(10):1341-2
17
UI - 11874075
AU - Cherchi PL; Marras V; Capobianco G; Ambrosini G; Piga M; Fadda GM;
TI -
Dessole S
Immunohistochemical evaluation of a new epithelial antigen, Ber-EP4, in
ovarian cancer: preliminary results.
SO - Eur J Gynaecol Oncol 2001;22(6):433-5
AD - Department of Pharmacology, Gynaecology and Obstetrics, University of
Sassari, Italy.
OBJECTIVE: To assess the immunohistochemical expression of Ber-EP4, a
new epithelial antigen in ovarian cancer. METHODS: We studied 25 cases
of ovarian cancer in which Ber-EP4, CEA and CA 125 were investigated by
an immunohistochemical method. We evaluated the correlations between
immunohistochemical positivity and grading, histotype and stage of
disease. RESULTS: CEA was positive in 5 out of 25 cases (20%), CA-125 in
17 out of 25 cases (68%) and Ber-EP4 in 14 out of 25 cases (56%).
Ber-EP4 was mainly present in mucinous tumors in comparison to serous
tumors (78.6% vs. 50%). Ber-EP4, as well as CA-125, were directly
proportional to tumor differentation (70% of positivity in G1 vs 37.5%
in G3 for the former and 80% in G1 vs 50% in G3 for the latter,
respectively), whereas CEA showed no relevant difference regarding the
grading. There were no differences among the three antigens studied with
regard to clinical stage. CONCLUSIONS: In our study Ber-EP4 was positive
in 14 out of 22 cases (63.6%) of the primary epithelial ovarian cancers
studied. The presence of this antigen seems to be related to histotype
and grading but not to clinical stage.
18
UI - 12078339
AU - Cianti C
TI -
[Treatment of ovarian cancer]
SO - Clin Ter 2002 Mar-Apr;153(2):135-44
AD - Ospedale S. Spirito in Sassia, Roma, Italia.
PURPOSE: To present an approach to the treatment of epithelial ovarian
cancer. DESIGN: A large number of studies in ovarian cancer have been
reviewed. RESULTS: Ovarian cancer is the most common fatal malignancy of
the female genital tract. The high mortality is due to the fact that the
most part of patients are diagnosed with advanced disease. Cytoreductive
surgery followed by platinum-based chemotherapy is the standard
therapeutic strategy for patients with advanced ovarian cancer.
Postsurgical residual disease is the most important prognostic factor.
The combination of Paclitaxel and Cisplatin or Carboplatin is currently
accepted as the standard chemotherapy for advanced ovarian cancer.
Second- look laparatomy should be reserved to patients enrolled in
clinical trial. Resistant disease remain the major cause of relapse and
death. Several drugs have been employed in second-line therapy; however,
the responses are generally short and survival is poor. CONCLUSIONS:
Future research should include new drugs or new combination regimens to
improve clinical outcomes and overall survival.
19
UI - 12094103
AU - Modugno F; Ness RB; Cottreau CM
TI -
Cigarette smoking and the risk of mucinous and nonmucinous epithelial
ovarian cancer.
SO - Epidemiology 2002 Jul;13(4):467-71
AD - Department of Epidemiology, Graduate School of Public Health, University
of Pittsburgh, 516A Parran Hall, 130 DeSoto Street, Pittsburgh, PA
15261, USA. fm@cs.cmu.edu
BACKGROUND: The association between cigarette smoking and ovarian cancer
may vary according to the histologic type of tumor. METHODS: We examined
cigarette smoking as a risk factor for both mucinous and nonmucinous
tumors in a population-based case-control study comparing 767 incident
cases of epithelial ovarian cancer with 1,367 community controls
frequency matched to cases by age and race. RESULTS: Smoking was
associated with mucinous tumors (odds ratio [OR] = 1.9; 95% confidence
interval [CI] = 1.3-2.9) but not with nonmucinous tumors (OR = 1.1; CI =
0.9-1.3). Furthermore, the odds ratios for smokers with mucinous tumors
increased with increasing pack-years of smoking (OR = 1.0, 1.9, and 2.7
for <5, 5-24, and > 24+ pack-years, respectively; P for trend = 0.01)
CONCLUSIONS: Cigarette smoking appears to be a risk factor for mucinous
but not for nonmucinous tumors.
20
UI - 12124814
AU - de la Hoya M; Sulleiro S; Osorio A; Diez O; Baiget M; Benitez J;
TI -
Diaz-Rubio E; Caldes T
Clustering of cancer-related mutations in a subset of BRCA1 alleles: a
study in the Spanish population.
SO - Int J Cancer 2002 Aug 10;100(5):618-9
AD - Laboratory of Molecular Oncology, Hospital Universitario San Carlos,
Madrid, Spain.
We have observed that the frequency of D17S855 short alleles (139 bp and
141 bp) in individuals carrying BRCA1 germline mutations is higher than
in controls (54% vs. 31%, p = 0.0004). By unambiguously establishing
mutation/D17S855 phase in 18 BRCA1-positive families, we find that most
(11 of 15 different mutations) BRCA1 defects are linked to chromosomes
with short alleles (OR = 8.21, 95% CI 1.97-39.32, p = 0.0007). We
suggest that BRCA1 mutations are not randomly distributed but clustered
in a subset of BRCA1 alleles that can be identified by D17S855
genotyping. Further analysis involving a larger set of mutations and
different populations are needed to clarify the relevance of this
unexpected finding. Copyright 2002 Wiley-Liss, Inc.
21
UI - 12146025
AU - Longatto Filho A; Alves VA; Kanamura CT; Nonogaki S; Bortolan J;
TI -
Lombardo V; Bisi H
Identification of the primary site of metastatic adenocarcinoma in
serous effusions. Value of an immunocytochemical panel added to the
clinical arsenal.
SO - Acta Cytol 2002 Jul-Aug;46(4):651-8
AD - Pathology Division, Alfredo Lutz Institute. longatto16@hotmail.com
OBJECTIVE: To use an immunocytochemical panel as ancillary method to
identify the origin of adenocarcinomas in serous effusions. STUDY
DESIGN: Serous effusion samples examined cytologically in the Department
of Surgical Pathology, A. C. Camargo Hospital, between 1966 and 1990,
were investigated. Of 4,297 cases, 2,317 were associated with
adenocarcinoma, and 1,099 were positive for adenocarcinoma by cytologic
examination. We selected a total of 248 cases of different origins to
subject to immunoreactions. A panel composed of CA-125, CA-19.9, HBME-1,
lactoferrin and BRST 2 was tested for the efficiency of these antibodies
under two conditions: the panel alone and associated with clinical data,
such as anatomic localization of the effusion (pleural or ascitic) and
patient sex and age. RESULTS: BRST 2 and lactoferrin were both positive
in 29.9% of cases of adenocarcinoma of breast origin; CA-125 and HBME-1
were 28.6% and 25.0% positive in cases of adenocarcinoma of the ovaries,
respectively. These immunoreactivities were highly specific when
compared to the others. The statistical significance of the results was
improved by information on the anatomic location of the effusions and
patient sex. CONCLUSION: Our data strongly indicate that BRST 2 and
lactoferrin are important components of an immunocytochemical panel used
to identify carcinomas of breast origin. Similarly, CA-125 and HBME-1
may be useful in suggesting the ovaries as possible primary sites.
22
UI - 12166471
AU - Anonymous
TI -
FDG positron emission tomography for the detection of ovarian cancer.
SO - TEC Bull (Online) 2002 Jul 8;19(2):10-3
23
UI - 12126844
AU - Elwood M
TI -
Proteomic patterns in serum and identification of ovarian cancer.
SO - Lancet 2002 Jul 13;360(9327):170; discussion 170-1
24
UI - 12082292
AU - Davidson B
TI -
Ovarian carcinoma and serous effusions. Changing views regarding tumor
progression and review of current literature.
SO - Anal Cell Pathol 2001;23(3-4):107-28
AD - Department of Pathology, The Norwegian Radium Hospital University of
Oslo, Montebello, N-0310 Oslo, Norway. bend@ulrik.uio.no
Carcinoma of the ovary is the leading cause of death from gynecological
cancer in western countries. Ovarian carcinoma is commonly associated
with the accumulation of fluid containing malignant cells in the
peritoneal, and not infrequently in the pleural cavity. The
differentiation of these cells from reactive mesothelial cells is at
times difficult. In addition, tumor progression in ovarian carcinoma and
the biological characteristics of carcinoma cells in effusions compared
to their counterparts in solid tumors are poorly understood. This review
details the current knowledge regarding diagnostic and biologic aspects
of effusion cytology, with emphasis on ovarian carcinoma. Results from
our first studies of effusions are subsequently presented. These attempt
to address several issues. First, to improve the diagnostic ability to
detect cancer cells in effusions using antibodies designed for the
differentiation of epithelial cells from mesothelial cells. Secondly, to
study genotypic and phenotypic differences between ovarian carcinoma
cells in effusions, solid primary tumors and metastatic lesions, as well
as to compare malignant cells in peritoneal and pleural effusions. These
studies of carbohydrate antigens, E-cadherin complex and matrix
metalloproteinases (MMP) attempted to evaluate whether ovarian carcinoma
cells in effusions possess true metastatic properties, or are similar to
the cells in primary tumors, thereby merely representing the result of a
shedding process. Finally, the prognostic role of these molecules was
studied in solid tumors from a patient cohort consisting of long- and
short-term survivors, followed for up to 20 years. Figure 1 on
http://www.esacp.org/acp/2001/23-3,4/davidson.htm.
25
UI - 11938448
AU - Nedelcu R; Liede A; Aube J; Finch A; Kwan E; Jack E; Narod SA; Randall
TI -
S; Hugel L; Clark K
BRCA mutations in Italian breast/ovarian cancer families.
SO - Eur J Hum Genet 2002 Feb;10(2):150-2
26
UI - 12124496
AU - Trabelsi A; Conan-Charlet V; Lhomme C; Morice P; Duvillard P; Sabourin
TI -
JC
[Peritoneal glioblastoma: recurrence of ovarian immature teratoma
(report of a case)]
SO - Ann Pathol 2002 Apr;22(2):130-3
AD - Service d'Anatomie et Cytologie pathologiques, Institut Gustave Roussy,
39 rue Camille Desmoulins, 94805 Villejuif Cedex, France.
Immature teratomas of the ovary represent less than 1% of all ovarian
teratomas. They contain several tissues that derive from the three
embryological layers: ectoderm, mesoderm and endoderm. They are rarely
associated with peritoneal implants that are essentially composed of
mature glial tissue, and of benign evolution. We report the case of a
37-year- old woman who presented an immature teratoma of the right ovary
that recurred seven years later as a malignant neuroepithelial
peritoneal tumor resembling a glioblastoma. Glioblastoma was diagnosed
at a second recurrence six months later. We discuss the
histopathogenesis of peritoneal implants secondary to immature
teratomas.
27
UI - 12144815
AU - Sit AS; Modugno F; Weissfeld JL; Berga SL; Ness RB
TI -
Hormone replacement therapy formulations and risk of epithelial ovarian
carcinoma.
SO - Gynecol Oncol 2002 Aug;86(2):118-23
AD - Graduate School of Public Health, University of Pittsburgh, Pennsylvania
15213, USA.
OBJECTIVE: Hormone replacement therapy (HRT) has been inconsistently
linked to ovarian cancer. Estrogen formulations in HRT vary in their
effects on estrogen-sensitive target tissues, such as the ovary. The aim
of the study is to evaluate the impact of various HRT formulations and
their characteristics of use on the risk of epithelial ovarian carcinoma
(EOC). METHODS: We assessed the association between the use of HRT and
the risk of invasive EOC in women participating in a population-based,
case-control study conducted in the Delaware Valley from 1994 to 1998.
Cases aged 45 or above at diagnosis (n = 484) were compared to community
controls (n = 926) frequency matched by age and area of residence.
Information on HRT formulation, timing, and duration were obtained by
in-person interview by trained interviewers. HRT formulations were
classified as opposed (estrogen + progestin) or unopposed (estrogen
alone). They were further categorized according to the estrogen
component as either conjugated equine estrogen (CEE), the most common
formulation, or non-CEE. Multivariate unconditional logistic regression
analyses were used to adjust for age at diagnosis, number of live
births, use of oral contraceptives, family history of ovarian carcinoma,
and history of tubal ligation. RESULTS: Overall, no association was
found between any use of HRT and EOC. Although use of unopposed non-CEE
was associated with a significant decrease in risk among hysterectomized
women (OR = 0.17, 95% CI = 0.04,0.82), this was not true for women with
an intact uterus (OR = 1.14, 95% CI = 0.44,2.98; P for interaction =
0.049). No significant differences in EOC risk were observed for other
HRT formulations. CONCLUSIONS: Our results did not suggest any
consistent pattern of altered risk for EOC and the overall use of HRT by
specific formulations of HRT.
28
UI - 12144816
AU - Aktas D; Guney I; Alikasifoglu M; Yuce K; Tuncbilek E; Ayhan A
TI -
CYP1A1 gene polymorphism and risk of epithelial ovarian neoplasm.
SO - Gynecol Oncol 2002 Aug;86(2):124-8
AD - Department of Genetics, Hacettepe University Medical School, 06100,
Sihhiye, Ankara, Turkey. dilekaktas6@hotmail.com
OBJECTIVE: Gene-environment interactions have been the focus of a number
of recent studies of the occurrence of human cancers, and an association
between the risk and the CYP1A1*3 polymorphism has been noticed for
several cancers. Previous studies suggest that estrogens are involved in
the etiology of ovarian cancer. The cytochrome P450 1A1 (CYP1A1) gene
polymorphism may play role in the development of epithelial ovarian
neoplasm by detoxification of polycyclic hydrocarbons and other
compounds and the concentration of estrogens and their metabolites.
Therefore, we assessed the association of CYP1A1 gene polymorphism in
patients with epithelial ovarian neoplasm in the Turkish populations
through a case-control study. METHODS: Using an allele-specific
polymerase chain reaction (PCR)-based method, CYP1A1*3 polymorphism, in
exon 7 of the gene, was analyzed in 117 epithelial ovarian neoplasm
patients and 202 control subjects. RESULTS: The CYP1A1 Ile/Val genotype
significantly increased the risk for patients with epithelial ovarian
neoplasm (OR 5.7, 95% CI 3.34-9.76). Furthermore, there were statistical
differences in the distribution of CYP1A1 Val/Val genotype among all
patients (OR 5.85, 95% CI 2.40-14.25). In other words, the presence of
the Val allele significantly increased the risk of epithelial ovarian
neoplasm. Among benign tumors, the frequency of Ile/Val and Val/Val
genotypes was found to be statistically significant with an ORs of 6.01
and 4.38 (95% CI 2.61-13.84 and 1.04-18.38, respectively). In the benign
serous ovarian tumors, patients with Ile/Val and Val/Val revealed a 7.2-
and 10.5-fold higher risk of having ovarian carcinoma (95% CI 2.22-23.40
and 2.16-51.19), respectively. In the benign mucinous ovarian carcinoma
patients, the frequency of Ile/Val was found to be statistically
significant with an OR of 5.15 (95% CI 1.75-15.16). However, no patient
with Val/Val genotype was observed in this group and no statistical
distribution was performed. Among borderline tumors, CYP1A1 Ile/Val
genotype significantly increased the risk for patients (OR 5.15, 95% CI
1.75-15.16). However, only one patient was observed with the Val/Val
allele and the frequency of this genotype was not found to be
statistically different with an OR of 2.50 (95% CI 0.27-22.64). Among
ovarian cancer patients, there were statistically differences in the
distribution of CYP1A1 Ile/Val and Val/Val genotypes (OR 5.73, 95% CI
3.04-10.76; and OR 7.42, 95% CI 2.80-19.66), suggesting that patients
carrying these genotypes were at increased risk for ovarian carcinoma.
In serous carcinoma, patients with CYP1A1 Ile/Val and Val/Val revealed a
6.5- and 10-fold higher risk of having ovarian cancer (OR 7.09, 95% CI
3.30-15.22; and OR 8.77, 95% CI 2.83-27.14). In mucinous carcinoma,
patients with CYP1A1 Ile/Val and Val/Val also revealed a 5.4 and 10.5
times higher risk of having ovarian cancer. There were no statistical
significance in the distribution of Val allele among endometroid-type
cancer patients. CONCLUSIONS: Our data, although based on a small number
of subjects, suggest that variant alleles of CYP1A1 gene in ovarian
epithelial cells, directly or through other components, may contribute
to initiation of ovarian carcinogenesis.
29
UI - 12144818
AU - Hefler LA; Ludwig E; Lampe D; Zeillinger R; Leodolter S; Gitsch G;
TI -
Koelbl H; Tempfer CB
Polymorphisms of the endothelial nitric oxide synthase gene in ovarian
cancer.
SO - Gynecol Oncol 2002 Aug;86(2):134-7
AD - Department of Obstetrics and Gynecology, University of Vienna Medical
School, Vienna, Austria.
OBJECTIVE: The free radical nitric oxide is known to be critically
involved in ovarian carcinogenesis by inducing apoptosis and by
mediating various cytostatic and cytotoxic effects, but also by
promoting growth, invasion, and metastasis. METHODS: We investigated two
polymorphisms (exon 7 Glu298Asp and a 27-bp repeat in intron 4) of the
gene encoding endothelial nitric oxide synthase (Nos3) in 130 patients
with ovarian cancer, 26 patients with borderline ovarian cancer, and 133
healthy age-matched Caucasian women using PCR and pyrosequencing,
respectively. RESULTS: Genotypes and allelic frequencies did not differ
between patients with ovarian cancer and controls. Within the ovarian
cancer group, however, the presence of at least one mutant allele of
intron 4 was associated with advanced tumor stage and positive lymph
node involvement, but not with tumor grading. The presence of the mutant
allele of exon 7 was not associated with the investigated
clinicopathological parameters. No correlation with patients' overall
and disease-free survival was ascertained. CONCLUSIONS: We are the first
to report on Nos3 polymorphisms in ovarian cancer. Allelic variation
within intron 4 of Nos3 is associated with an advanced tumor stage and
positive lymph node involvement in ovarian cancer.
30
UI - 12144824
AU - Kamazawa S; Kigawa J; Kanamori Y; Itamochi H; Sato S; Iba T; Terakawa N
TI -
Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based
chemotherapy for patients with ovarian cancer.
SO - Gynecol Oncol 2002 Aug;86(2):171-6
AD - Department of Obstetrics and Gynecology, Tottori University School of
Medicine, Yonago, 683-8504, Japan.
OBJECTIVE: The objective of this study was to determine the relationship
between multidrug resistance and sensitivity to paclitaxel (PTX) in
ovarian cancer. METHODS: We used human ovarian adenocarcinoma cell
lines, KF, a PTX-resistant cell line (KFTx), SK-OV-3, and KOC7c.
Additionally, 27 patients with ovarian cancer who had residual disease
were examined. All patients underwent postoperative chemotherapy
consisting of 175 mg/m(2) PTX and area under curve (AUC) 5 carboplatin.
The sensitivity of the cells to PTX or cisplatin (CDDP) was determined
by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
assay. mRNA expression of multidrug resistance gene-1 (MDR-1) and
multidrug resistance-associated protein-1 (MRP-1) and MRP-2 was
determined by reverse transcription-polymerase chain reaction.
beta-Tubulin polymerization and Bcl-2 phosphorylation were examined by
Western blot analysis. RESULTS: Compared with KF, the IC(50) to PTX was
5.5-fold higher for KFTx, 0.3-fold for SK-OV-3, and 52.1-fold for KOC7c.
The IC(50) to CDDP was 0.7-, 4.2-, and 5.8-fold, respectively.
Expression of the MDR-1 gene was clearly observed in KFTx and KOC7c.
Expression of MRP-1 was observed in SK-OV-3 and KOC7c. Expression of
MRP-2 was detected only in KOC7c. CDDP enhanced beta-tubulin
polymerization induced by PTX in CDDP-sensitive cells. Bcl-2
phosphorylation appeared after exposure to IC(50) PTX in all cells.
Twenty-one patients responded to chemotherapy and six did not.
Expression of the MDR-1 gene for nonresponders was significantly higher
than that for responders (260.0 +/- 191.6 vs 9.3 +/- 21.8). With the
cutoff value of MDR-1 expression at 100, the predictive value for
chemoresponse was 96%. Expression of the MRP-1 and MRP-2 genes did not
differ between nonresponders and responders. CONCLUSION: MDR-1 gene
expression may be a useful predictor for PTX-based chemotherapy.
31
UI - 12144829
AU - Donovan KA; Greene PG; Shuster JL; Partridge EE; Tucker DC
TI -
Treatment preferences in recurrent ovarian cancer.
SO - Gynecol Oncol 2002 Aug;86(2):200-11
AD - Department of Psychology, University of Alabama at Birmingham, 35294,
USA.
OBJECTIVES: In the case of recurrent ovarian cancer, salvage therapy
represents the potential to trade off between quality and quantity of
life. Patient and physician face a choice between chemotherapy directed
at slowing disease progression and supportive or palliative care that
focuses on symptom management. To date, no studies have investigated the
effects of best supportive care on ovarian cancer patients' quality of
life and length of life as compared to salvage therapy. In other
cancers, both quantity and quality of life considerations have been
shown to affect treatment preferences. METHODS: Using a decision board,
we assessed preferences for salvage therapy or palliative care in the
case of recurrent ovarian cancer among 81 ovarian cancer patients
receiving first-line chemotherapy and 75 Noncancer Controls. RESULTS:
Compared to Noncancer Controls, ovarian cancer patients overwhelmingly
preferred salvage therapy; quantity of life was of primary importance.
In both groups, preference was not related to age, marital status,
number of children, or employment status. On average, patients indicated
they would switch from salvage therapy to palliative care when the
median survival associated with salvage therapy was reduced to 5 months.
Noncancer Controls would switch significantly sooner, when the median
increment in survival period was reduced to 8 months. Switchpoint was
not associated with life satisfaction, quality of life, or psychological
or spiritual well-being in either group. CONCLUSIONS: The majority of
women, independent of a cancer diagnosis, indicated a desire for
continuing aggressive treatment, despite poor outcomes. Quality of life
was of secondary importance, especially among ovarian cancer patients.
32
UI - 12144830
AU - Tiller K; Meiser B; Butow P; Clifton M; Thewes B; Friedlander M; Tucker
TI -
K
Psychological impact of prophylactic oophorectomy in women at increased
risk of developing ovarian cancer: a prospective study.
SO - Gynecol Oncol 2002 Aug;86(2):212-9
AD - Department of Medical Oncology, Prince of Wales Hospital, Sydney,
Australia. k.tiller@unsw.edu.au
OBJECTIVES: The objectives of this study were twofold: to prospectively
assess whether expressed intention to undergo prophylactic oophorectomy
translated into uptake and to evaluate the psychological impact of the
procedure in a sample of unaffected women with a strong family
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