Fluorescence in situ hybridization test for detection of endometrial carcinoma cells by non-invasive vaginal swab.

Endometrial cancer (EC) is the most common gynaecological malignancy with increasing incidence in developed countries. As gold standard, hysteroscopy confirms only 30% of suspected ECs. The detection of EC cells in the vagina by fluorescence in situ hybridization (FISH) after a smear test could reduce invasive procedures in the future. Using array-based comparative genome hybridization (aCGH) on 65 endometrial carcinomas, most frequently imbalanced regions of the tumour genome were identified. Bacterial artificial chromosomes were used to generate FISH-probes homologue to these human regions. The FISH test was hybridized on swabs specimens collected from the vaginal cavity. Samples from six patients without EC were selected as a negative control and on 13 patients with known EC as a positive control. To distinguish between benign and EC cases, the cut-off value has been defined. A first validation of this EC-FISH Test was performed with swabs from 41 patients with suspected EC. The most common genomic imbalances in EC are around the CTNNB1, FBXW7 and APC genes. The cut-off is defined at 32% of analysed cells without diploid signal pattern. This differs significantly between the positive and negative controls (p < 0.001). In a first validation cohort of 41 patients with suspected EC, the EC-FISH Test distinguishes patients with and without EC with a sensitivity of 91% and a specificity of 83%. The negative predictive value is 96%. This is the first report of a non-invasive EC-FISH Test to predict EC in women with suspected EC.

Challenges and Controversies in the Surgical Treatment of Cervical Cancer: Open Radical Hysterectomy versus Minimally Invasive Radical Hysterectomy.

OBJECTIVE: The aim of the study was to perform a systematic assessment of disease-free survival (DFS), overall survival, and morbidity rates after open radical hysterectomy (ORH) and minimally invasive surgery (MIS) for early-stage cervical cancer and discuss with experts the consequences of the LACC trial (published by Ramirez et al. in 2018) on clinical routine. METHODS: A total of 5428 records were retrieved. After exclusion based on text screening, four records were identified for inclusion. Five experts from three independent large-volume medical centers in Europe were interviewed for their interpretation of the LACC trial. RESULTS: The LACC trial showed a significantly higher risk of disease progression with MIS compared to ORH (HR 3.74, 95% CI 1.63 to 8.58). This was not seen in one epidemiological study and was contradicted by one prospective cohort study reported by Greggi et al. A systematic review by Zhang et al. mentioned a similar DFS for robot-assisted radical hysterectomy (RRH) and LRH. Recurrence rates were significantly higher with MIS compared to ORH in the LACC trial (HR 4.26, 95% CI 1.44 to 12.60). In contrast, four studies presented by Greggi reported no significant difference in recurrence rates between LRH/RRH and ORH, which concurred with the systematic reviews of Zhang and Zhao. The experts mentioned various limitations of the LACC trial and stated that clinicians were obliged to provide patients with detailed information and ensure a shared decision-making process. CONCLUSIONS: The surgical treatment of early-stage cervical cancer remains a debated issue. More randomized controlled trials (RCT) will be needed to establish the most suitable treatment for this condition.

Extracellular Juxtamembrane Segment of ADAM17 Interacts with Membranes and Is Essential for Its Shedding Activity.

A wide variety of biological processes including differentiation, regeneration, and cancer progression are regulated by shedding of membrane-anchored proteins. One of the major sheddases is A Disintegrin And Metalloprotease-17 (ADAM17) whose extracellular region consists of a pro-, a catalytic, a disintegrin-, and a membrane-proximal domain (MPD) as well as a short juxtamembrane segment of 17 amino acid residues that has been named "Conserved ADAM-seventeeN Dynamic Interaction Sequence" (CANDIS). This segment is involved in substrate recognition. Key mediators of inflammation including interleukin-6 receptor (IL-6R) and tumor necrosis factor (TNF-α) are substrates of ADAM17. The shedding activity of ADAM17 is regulated by the conformation of the membrane-proximal domain preceding the CANDIS segment. Here, we show that CANDIS, besides being involved in substrate recognition, is able to interact with lipid bilayers in vitro and that this property could be involved in regulating ADAM17 shedding activity.