Functional OCT4-specific CD4 and CD8 T cells in healthy controls and ovarian cancer patients.

The identification of growth and differentiation pathways that are responsible for the proliferation and survival of cancer stem cells (CSCs) has opened avenues for the discovery of novel therapeutic targets. In the initial phase of an anticancer immune response, T cells specific for tumor-associated antigens develop in patients and, at least under selected circumstances, are able to eliminate malignant cells. However, it remains unknown whether CSC-specific T cells are also operational.

Cervical cytology in serous and endometrioid endometrial cancer.

The aim of this study was to determine the frequency of abnormal cervical cytology in preoperative cervical cytology of patients diagnosed with uterine papillary serous carcinoma (UPSC) and endometrioid endometrial carcinoma (EEC). In addition, associations between abnormal cervical cytology and clinicopathologic factors were evaluated. In this multicentre study, EEC patients diagnosed at two hospitals from 1999 to 2009 and UPSC patients diagnosed at five hospitals from 1992 to 2009, were included.

Linear regression of postevacuation serum human chorionic gonadotropin concentrations predicts postmolar gestational trophoblastic neoplasia.

Objective: Currently, human chorionic gonadotropin (hCG) follow-up after evacuation of hydatidiform moles is essential to identify patients requiring chemotherapeutic treatment for gestational trophoblastic neoplasia (GTN). We propose a model based on linear regression of postevacuation serum hCG concentrations for the prediction of GTN.

Methods: One hundred thirteen patients with at least 3 serum samples from days 7 to 28 after evacuation were selected from the Dutch Central Registry for Hydatidiform Moles (1994-2009).

Tubal ligation and risk of ovarian cancer subtypes: a pooled analysis of case-control studies.

Background: Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes.

Methods: We pooled primary data from 13 population-based case-control studies, including 10,157 patients with ovarian cancer (7942 invasive; 2215 borderline) and 13,904 control women.

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants.

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer.

Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array.

Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer.

HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.

Identification and molecular characterization of a new ovarian cancer susceptibility locus at 17q21.31.

Epithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility.

Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer.

Background: There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied.

Methods: Data from 14 ovarian cancer case-control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histologic subtypes.

Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case-control studies.

Purpose: The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology.

Methods: We used data from 21 case-control studies of ovarian cancer (19,066 controls, 11,972 invasive and 2,752 borderline cases).

Absolute depth of myometrial invasion in endometrial cancer is superior to the currently used cut-off value of 50%.

Objective: In endometrial carcinoma, myometrial invasion is a well known predictor of recurrence, and important in the decision making for adjuvant treatment. According to the FIGO staging system, myometrial invasion is expressed as invasion of <50%> of the myometrium (50%MI). It has been suggested to use the absolute depth of invasion (DOI), or the tumor free distance to the serosa (TFD).

Interobserver variability and the effect of education in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia.

No published data concerning intraobserver and interobserver variability in the histopathological diagnosis of differentiated vulvar intraepithelial neoplasia (DVIN) are available, although it is widely accepted to be a subtle and difficult histopathological diagnosis. In this study, the reproducibility of the histopathological diagnosis of DVIN is evaluated. Furthermore, we investigated the possible improvement of the reproducibility after providing guidelines with histological characteristics and tried to identify histological characteristics that are most important in the recognition of DVIN.

Prospective follow-up of 2,065 young unscreened women to study human papillomavirus incidence and clearance.

Human papillomavirus (HPV) is a necessary factor in the development of cervical intraepithelial neoplasia and cervical cancer. However, HPV is also a very common sexually transmitted virus and many women clear their infection. To study HPV incidence and clearance, 2,065 women, aged 18-29 years, were followed for 12 months and were asked to provide a self-collected cervico-vaginal sample and fill-out a questionnaire every 3 months.

Human papillomavirus detection in pregnant women: a prospective matched cohort study.

Objective: To study the prevalence, incidence, and clearance of human papillomavirus (HPV) in pregnant and nonpregnant women.

Methods: In this prospective matched cohort study, 51 women, became pregnant during follow-up of an HPV epidemiology study (n=2065), and 51 matched nonpregnant women were included. All women provided 3-monthly cervicovaginal self-samples and completed a questionnaire.

Pure compared with mixed serous endometrial carcinoma: two different entities?

Objective: To analyze whether mixed compared with pure uterine papillary serous carcinoma histology affects clinical outcome, and to assess uterine papillary serous carcinoma for its association with the precursor lesion endometrial intraepithelial carcinoma.

Methods: A multi-institution observational study of stage I-IV uterine papillary serous carcinoma patients was performed. Histopathologic slides were reviewed by four expert pathologists, with determination of the percentage serous histology within each tumor.

Comparing cisplatin-based combination chemotherapy with EMA/CO chemotherapy for the treatment of high risk gestational trophoblastic neoplasia.

Background: Cisplatin-based chemotherapy (etoposide 100 mg/m(2) days 1-5, methotrexate 300 mg/m(2) day 1, cyclophosphamide 600 mg/m(2) day 1, actinomycin D 0.6 mg/m(2) day 2 and cisplatin 60 mg/m(2) day 4, EMACP) was compared to EMA/CO (etoposide 100 mg/m(2) days 1-2, methotrexate 300 mg/m(2) day 1 and actinomycin D 0.5 mg i.

Endometrioid endometrial carcinoma with atrophic endometrium and poor prognosis.

Objective: Type I endometrial carcinomas are characterized by endometrioid histology, develop from hyper-plastic endometrium, and have a good prognosis. Type II, nonendometrioid carcinomas, arise in atrophic endometrium and have a poor prognosis. However, approximately 20% of cases do not fit within this dualistic model and include endometrioid carcinomas associated with recurrence and possibly with atrophy.

Fatal cases of gestational trophoblastic neoplasia over four decades in the Netherlands: a retrospective cohort study.

Objective: To describe fatal cases of gestational trophoblastic neoplasia (GTN) over four decades and evaluate whether treatment was given according to the protocol and reveal possible implications for future management.

Design: Retrospective cohort study.

Setting: The Netherlands.

Preoperative CA-125 predicts extra-uterine disease and survival in uterine papillary serous carcinoma patients.

Objective: We determined the clinical utility of preoperative serum CA-125 as predictor of extra-uterine disease and as prognosticator for survival in patients with uterine papillary serous carcinoma (UPSC).

Methods: Patients diagnosed with UPSC, identified between 1992 and 2009, and with preoperative CA-125 measurement were included. A receiver operator characteristic (ROC) curve was used to quantify marker performance.

Impact of routine follow-up examinations on life expectancy in ovarian cancer patients: a simulation study.

Objective: The clinical benefit of routine follow-up in patients treated for ovarian cancer is subject to debate. In this study, the magnitude of the potential survival benefit of routine examinations was evaluated by Markov modeling.

Methods: The clinical course of ovarian cancer was simulated using a 4-state nonstationary Markov model.

Genome-wide association study for ovarian cancer susceptibility using pooled DNA.

Recent Genome-Wide Association Studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate- or low-penetrance variants exist among the subset of single-nucleotide polymorphisms (SNPs) not well tagged by the genotyping arrays used in the previous studies, which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high-density Illumina 1M-Duo array.

Highly sulfated chondroitin sulfates, a novel class of prognostic biomarkers in ovarian cancer tissue.

Objective: Clinical decision making in ovarian cancer needs new (prognostic) biomarkers. Although the search for biomarkers has traditionally focused on tumor cells, their surrounding contains important information as well. Glycosaminoglycans, heterogeneous polysaccharides which are abundantly present in the stromal compartment, are indicated in several pathological processes including cancer.

Human chorionic gonadotropin (hCG) regression normograms for patients with high-risk gestational trophoblastic neoplasia treated with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) chemotherapy.

Background: We present normograms for human chorionic gonadotropin (hCG) regression in patients with high-risk gestational trophoblastic neoplasia (GTN) successfully treated with multiagent chemotherapy in order to predict treatment resistance.

Patients And Methods: We collected data for 46 patients with high-risk GTN treated with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine) who had hCG values available. Patients were classified as having methotrexate (MTX)-resistant disease (n = 22) or primary high-risk disease (n = 24).

Tubal epithelial lesions in salpingo-oophorectomy specimens of BRCA-mutation carriers and controls.

Objective: A precursor lesion for ovarian carcinoma, tubal intraepithelial carcinoma (TIC), has been identified in BRCA-mutation carriers undergoing prophylactic bilateral salpingo-oophorectomy (pBSO). Other lesions were also identified in fallopian tubes, but different terminology, interpretation, and lack of knowledge of normal epithelium, have hampered to unravel their possible role in carcinogenesis. The aim of this study is to classify tubal epithelial lesions in BRCA-mutation carriers and controls to enable comparison of prevalence, area of localization, and possible malignant potential.

Patients' experience of psoriasis in the genital area.

Background: Psoriasis in the genital area is often neglected, although it bothers a substantial number of patients.

Objective: To study both the role of the physician in the treatment of genital psoriasis and the symptom intensity of these lesions as experienced by the patients.

Methods: A detailed self-administered questionnaire (containing items on the role of the physician and genital symptom intensity, range 0-10) was filled in by members of the Dutch Psoriasis Society.