European Federation for Colposcopy and Institut national du Cancer (INCA).

Endometrial cancer is the most common malignancy of the lower female reproductive tract. The tumor suppressor FOXO1 is downregulated in endometrial cancer compared with normal endometrium but the underlying mechanisms are not well understood. Using microRNA (miR) target prediction algorithms, we identified several miRs that potentially bind the 3′-untranslated region of FOXO1 transcripts. Expression profiling of normal and malignant endometrial samples by quantitative real-time PCR and Northern blot analysis revealed an inverse correlation between the levels of FOXO1 protein and the abundance of several of the in silico-predicted miRs, suggesting that loss of FOXO1 expression in endometrial cancer may be mediated by miRs. To determine the role of candidate miRs, we used the endometrial cancer cell lines HEC-1B and Ishikawa, which express FOXO1 at high and low levels, respectively. Expression of miR-9, miR-27, miR-96, miR-153, miR-182, miR-183, or miR-186, but not miR-29a, miR-128, miR-152, or miR-486 mimetics in HEC-1B cells was sufficient to significantly reduce the abundance of FOXO1. Conversely, FOXO1 expression was efficiently restored in the Ishikawa cell line upon simultaneous inhibition of miR-9, miR-27, miR-96, miR-153, miR-183, and miR-186. Moreover, induction of FOXO1 in Ishikawa cells by miR inhibitors was accompanied by G 1 cell cycle arrest and cell death, and was attenuated by the small interfering RNA-mediated downregulation of FOXO1 expression. Our findings identify several miRs overexpressed in endometrial cancer that function in concert to repress FOXO1 expression. Further, aberrant miR expression results in deregulated cell cycle control and impaired apoptotic responses, and thus, may be central to endometrial tumorigenesis.

PurposeThere are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best to manage the risk of gynecological cancer in women with Lynch syndrome. The Manchester International Consensus Group was convened in April 2017 to address this unmet need. The aim of the Group was to develop clear and comprehensive clinical guidance regarding the management of the gynecological sequelae of Lynch syndrome based on existing evidence and expert opinion from medical professionals and patients.MethodsStakeholders from Europe and North America worked together over a two-day workshop to achieve consensus on best practice.ResultsGuidance was developed in four key areas: (1) whether women with gynecological cancer should be screened for Lynch syndrome and (2) how this should be done, (3) whether there was a role for gynecological surveillance in women at risk of Lynch syndrome, and (4) what preventive measures should be recommended for women with Lynch syndrome to reduce their risk of gynecological cancer.ConclusionThis document provides comprehensive clinical guidance that can be referenced by both patients and clinicians so that women with Lynch syndrome can expect and receive appropriate standards of care.

No abstract

Uterine transplantation restores reproductive anatomy in women with absolute uterine factor infertility and allows the opportunity to conceive, experience gestation, and acquire motherhood. The number of cases being performed is increasing exponentially, with detailed outcomes from 45 cases, including nine live births, now available. In light of the data presented herein, including detailed surgical, immunosuppressive and obstetric outcomes, the feasibility of uterine transplantation is now difficult to refute. However, it is associated with significant risk with more than one-quarter of grafts removed because of complications, and one in ten donors suffering complications requiring surgical repair.Tweetable abstract Uterine transplantation is feasible in women with uterine factor infertility, but is associated with significant risk of complication.

BACKGROUND Characterizing ovarian pathology is fundamental to optimizing management in both pre- and post-menopausal women. Inappropriate referral to oncology services can lead to unnecessary surgery or overly radical interventions compromising fertility in young women, whilst the consequences of failing to recognize cancer significantly impact on prognosis. By reflecting on recent developments of new diagnostic tests for preoperative identification of malignant disease in women with adnexal masses, we aimed to update a previous systematic review and meta-analysis. METHODS An extended search was performed in MEDLINE (PubMed) and EMBASE (OvidSp) from March 2008 to October 2013. Eligible studies provided information on diagnostic test performance of models, designed to predict ovarian cancer in a preoperative setting, that contained at least two variables. Study selection and extraction of study characteristics, types of bias, and test performance was performed independently by two reviewers. Quality was assessed using a modified version of the QUADAS assessment tool. A bivariate hierarchical random effects model was used to produce summary estimates of sensitivity and specificity with 95% confidence intervals or plot summary ROC curves for all models considered. RESULTS Our extended search identified a total of 1542 new primary articles. In total, 195 studies were eligible for qualitative data synthesis, and 96 validation studies reporting on 19 different prediction models met the predefined criteria for quantitative data synthesis. These models were tested on 26 438 adnexal masses, including 7199 (27%) malignant and 19 239 (73%) benign masses. The Risk of Malignancy Index (RMI) was the most frequently validated model. The logistic regression model LR2 with a risk cut-off of 10% and Simple Rules (SR), both developed by the International Ovarian Tumor Analysis (IOTA) study, performed better than all other included models with a pooled sensitivity and specificity, respectively, of 0.92 [95% CI 0.88-0.95] and 0.83 [95% CI 0.77-0.88] for LR2 and 0.93 [95% CI 0.89-0.95] and 0.81 [95% CI 0.76-0.85] for SR. A meta-analysis of centre-specific results stratified for menopausal status of two multicentre cohorts comparing LR2, SR and RMI-1 (using a cut-off of 200) showed a pooled sensitivity and specificity in premenopausal women for LR2 of 0.85 [95% CI 0.75-0.91] and 0.91 [95% CI 0.83-0.96] compared with 0.93 [95% CI 0.84-0.97] and 0.83 [95% CI 0.73-0.90] for SR and 0.44 [95% CI 0.28-0.62] and 0.95 [95% CI 0.90-0.97] for RMI-1. In post-menopausal women, sensitivity and specificity of LR2, SR and RMI-1 were 0.94 [95% CI 0.89-0.97] and 0.70 [95% CI 0.62-0.77], 0.93 [95% CI 0.88-0.96] and 0.76 [95% CI 0.69-0.82], and 0.79 [95% CI 0.72-0.85] and 0.90 [95% CI 0.84-0.94], respectively. CONCLUSIONS An evidence-based approach to the preoperative characterization of any adnexal mass should incorporate the use of IOTA Simple Rules or the LR2 model, particularly for women of reproductive age.

Incomplete healing of the scar is a recognized sequel of Cesarean section (CS) and may be associated with

RNA-binding proteins (RBPs) are increasingly identified as post-transcriptional drivers of cancer progression. The RBP LARP1 is an mRNA stability regulator, and elevated expression of the protein in hepatocellular and lung cancers is correlated with adverse prognosis. LARP1 associates with an mRNA interactome that is enriched for oncogenic transcripts. Here we explore the role of LARP1 in epithelial ovarian cancer, a disease characterized by the rapid acquisition of resistance to chemotherapy through the induction of pro-survival signalling. We show, using ovarian cell lines and xenografts, that LARP1 is required for cancer cell survival and chemotherapy resistance. LARP1 promotes tumour formation in vivo and maintains cancer stem cell-like populations. Using transcriptomic analysis following LARP1 knockdown, cross-referenced against the LARP1 interactome, we identify BCL2 and BIK as LARP1 mRNA targets. We demonstrate that, through an interaction with the 3′ untranslated regions (3′ UTRs) of BCL2 and BIK, LARP1 stabilizes BCL2 but destabilizes BIK with the net effect of resisting apoptosis. Together, our data indicate that by differentially regulating the stability of a selection of mRNAs, LARP1 promotes ovarian cancer progression and chemotherapy resistance.