Biomarkers of endometriosis REPLY

Department of Development and Regeneration, Sexual, Pelvic, Reproductive, and Family Studies, University Hospital Gasthuisberg, Leuven, Belgium.
Fertility and sterility (Impact Factor: 4.59). 02/2013; 100(4). DOI: 10.1016/j.fertnstert.2013.01.097
Source: PubMed


A noninvasive test for endometriosis would be useful for the early detection of endometriosis in symptomatic women who have pelvic pain and/or subfertility with normal ultrasound results. This would include nearly all cases of minimal-to-mild endometriosis, some cases of moderate-to-severe endometriosis without a clearly visible ovarian endometrioma, and cases with pelvic adhesions and/or other pelvic pathology that might benefit from surgery to improve pelvic pain and/or subfertility. This overview discusses the diagnostic performance of noninvasive or semi-invasive tests for endometriosis, including panels of known peripheral blood biomarkers, protein/peptide markers discovered by proteomics, miRNA, and endometrial nerve fiber density. Tests with high sensitivity and acceptable specificity have been developed; some have been validated in independent populations and are therefore promising. To make real progress, international agreement on biobank development is needed for standard operating procedures for the collection, treatment, storage, and analysis of tissue samples and for detailed clinical phenotyping of these samples. Furthermore, it is necessary to validate the diagnostic accuracy of any promising test prospectively in an independent symptomatic patient population with subfertility and/or pain without clear ultrasound evidence of endometriosis and with a clinical indication for surgery, divided into cases with laparoscopically and histologically confirmed endometriosis and controls with laparoscopically confirmed absence of endometriosis.

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Available from: Philippa T K Saunders, Feb 19, 2014
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    • "A plethora of biochemical differences in the peripheral circulation , peritoneal fluid, and endometrial tissues of women with endometriosis versus healthy controls has been demonstrated [40] [41] [42] many of which are related to a chronic inflammatory reaction [43] [44] [45] [46] [47] [48] [49] [50]. Other biomarkers that have been examined include vascular endothelial growth factor (VEGF) [51] [52] [53], glycodelin [54] [55] [56], different biomarkers in the apoptosis pathway including the annexin family [57– 59], and soluble intracellular adhesion molecule-1 [60] [61] [62] [63]. "
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    ABSTRACT: In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women’s health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research vigor into the identification of novel biomarkers of disease and therapeutic options. Herein we propose a number of opportunities for research and development of new therapeutics to address the unmet needs in the treatment of endometriosis per se and its ancillary risks for other diseases in women across the lifespan.
    Full-text · Article · May 2015 · BioMed Research International
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    • "Several studies investigating potential biomarkers for endometriosis have included inflammatory markers or immunological cells in the peritoneal fluid (PF) and/or peripheral blood samples of patients with and without endometriosis (Seeber et al., 2008; May et al., 2010; Fassbender et al., 2013; Toor et al., 2014; Ejzenberg et al., 2013; Podgaec et al., 2012). Many cytokines have been used as putative markers of endometriosis, especially the chemokines, a family of small chemotactic cytokines or signaling proteins (Borrelli et al., 2013). "
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    ABSTRACT: Chemokines have been associated with endometriosis. Our study was aimed at evaluating the levels of six chemokines - CXCL8 (IL-8), CXCL12 (SDF-1), CCL2 (MCP-1), CCL5 (RANTES), CCL19 (MIP-3β), and CCL21 (6-Ckine) - in the peritoneal fluid (PF) of patients with and controls without endometriosis by multiplexed cytokine assay. In this retrospective case-control study conducted at the Charité University Hospital, patients (n=36) and controls (n=27) were enrolled. The patients were separated into groups according to stage of the disease: I-II (n=21), III-IV (n=15), and according to clinical findings: peritoneal endometriosis (PE; n=7), deep-infiltrating endometriosis (DIE) affecting the retrocervical area (n=13) or the bowel/rectovaginal site (n=14). The subjects were also separated according to the cycle phase: follicular (n=14) or luteal (n=8) and the previous use (n=25) or not (n=38) of hormones. PF was collected from all subjects (n=63) consecutively during laparoscopy. The concentration of chemokines in the PF was assessed using Luminex(®) x-MAP(®) technology. Sensitivity and specificity were calculated. A model of multiple logistic regressions estimated the odds of endometriosis for each combination of the chemokines detected. We observed significantly higher concentrations of IL-8 (p<0.001), MCP-1 (p=0.014), and MIP-3β (p=0.022) in the PF of women with endometriosis than in the controls. A joint evaluation revealed that elevated levels of the three chemokines had a positive endometriosis prediction value of 89.1%. The combined assessment of MCP-1, MIP-3β, and IL-8 concentration in PF improved the likelihood of identifying patients with endometriosis. Future studies should investigate this panel in peripheral blood samples. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Full-text · Article · Feb 2015 · Journal of Reproductive Immunology
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    • "A biomarker that is simple to measure could help clinicians to diagnose or exclude endometriosis ; it might also allow the effects of treatment to be monitored. If effective, such a marker or panel of markers could prevent unnecessary diagnostic procedures and/or recognize treatment failure at an early stage [4] [5] [6] [7]. A biomarker is a measurable ''biologic marker'' that correlates with a specific outcome or state of the disease [17]. "
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    ABSTRACT: Objectives: Endometriosis is a common disorder amongst women of reproductive age. Despite extensive research, no reliable blood tests currently exist for the diagnosis of endometriosis Study design: We report several new approaches enabling study of cell specific characteristic of endometrial cells, introducing enrichment and culturing of viable circulating endometrial cells (CECs) isolated from peripheral blood (PB) and peritoneal endometrial cells (PECs) from peritoneal washing (PW). Size-based enrichment method (MetaCell(®), Czech Republic) has been used for the filtration of PB and PW in patients with diagnosed endometriosis. Results: The PECs were found in the PW in all of the tested patients (n=17), but CECs) only in 23.5% (4/17) cases. Their endometrial origin has been proved by immunohistochemistry. PECs were successfully cultured in vitro directly on the separating membrane (9/17) exhibiting both endometrial cell phenotypes: stromal and glandular within the culture. CECs were successfully cultured in the two of the four positive cases, but in none of them confluence has been reached. The occurrence in CECs in PB is clear and very specific evidence of an active endometrial disease. Conclusions: We demonstrated efficient, quick and user friendly endometrial cells capture platform based on a cell size. Furthermore, we demonstrated an ability to culture the captured cells, a critical requirement for post-isolation cellular analysis directed to better understanding of endometriosis pathogenesis.
    Full-text · Article · Aug 2014 · European Journal of Obstetrics & Gynecology and Reproductive Biology
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