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      World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project: IV. Tissue collection, processing, and storage in endometriosis research

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          Abstract

          Objective

          To harmonize standard operating procedures (SOPs) and standardize the recording of associated data for collection, processing, and storage of human tissues relevant to endometriosis.

          Design

          An international collaboration involving 34 clinical/academic centers and three industry collaborators from 16 countries on five continents.

          Setting

          In 2013, two workshops were conducted followed by global consultation, bringing together 54 leaders in endometriosis research and sample processing from around the world.

          Patient(s)

          None.

          Intervention(s)

          Consensus SOPs were based on: 1) systematic comparison of SOPs from 24 global centers collecting tissue samples from women with and without endometriosis on a medium or large scale (publication on >100 cases); 2) literature evidence where available, or consultation with laboratory experts otherwise; and 3) several global consultation rounds.

          Main Outcome Measure(s)

          Standard recommended and minimum required SOPs for tissue collection, processing, and storage in endometriosis research.

          Result(s)

          We developed “recommended standard” and “minimum required” SOPs for the collection, processing, and storage of ectopic and eutopic endometrium, peritoneum, and myometrium, and a biospecimen data collection form necessary for interpretation of sample-derived results.

          Conclusion(s)

          The EPHect SOPs allow endometriosis research centers to decrease variability in tissue-based results, facilitating between-center comparisons and collaborations. The procedures are also relevant to research into other gynecologic conditions involving endometrium, myometrium, and peritoneum. The consensus SOPs are based on the best available evidence; areas with limited evidence are identified as requiring further pilot studies. The SOPs will be reviewed based on investigator feedback and through systematic triannual follow-up. Updated versions will be made available at: http://endometriosisfoundation.org/ephect.

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          Most cited references67

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          Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

          The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.
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            Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field.

            Colorectal cancer is a complex disease resulting from somatic genetic and epigenetic alterations, including locus-specific CpG island methylation and global DNA or LINE-1 hypomethylation. Global molecular characteristics such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), global DNA hypomethylation, and chromosomal instability cause alterations of gene function on a genome-wide scale. Activation of oncogenes including KRAS, BRAF and PIK3CA affects intracellular signalling pathways and has been associated with CIMP and MSI. Traditional epidemiology research has investigated various factors in relation to an overall risk of colon and/or rectal cancer. However, colorectal cancers comprise a heterogeneous group of diseases with different sets of genetic and epigenetic alterations. To better understand how a particular exposure influences the carcinogenic and pathologic process, somatic molecular changes and tumour biomarkers have been studied in relation to the exposure of interest. Moreover, an investigation of interactive effects of tumour molecular changes and the exposures of interest on tumour behaviour (prognosis or clinical outcome) can lead to a better understanding of tumour molecular changes, which may be prognostic or predictive tissue biomarkers. These new research efforts represent 'molecular pathologic epidemiology', which is a multidisciplinary field of investigations of the inter-relationship between exogenous and endogenous (eg, genetic) factors, tumoural molecular signatures and tumour progression. Furthermore, integrating genome-wide association studies (GWAS) with molecular pathological investigation is a promising area (GWAS-MPE approach). Examining the relationship between susceptibility alleles identified by GWAS and specific molecular alterations can help elucidate the function of these alleles and provide insights into whether susceptibility alleles are truly causal. Although there are challenges, molecular pathological epidemiology has unique strengths, and can provide insights into the pathogenic process and help optimise personalised prevention and therapy. In this review, we overview this relatively new field of research and discuss measures to overcome challenges and move this field forward.
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              Laser capture microdissection.

              Laser capture microdissection (LCM) under direct microscopic visualization permits rapid one-step procurement of selected human cell populations from a section of complex, heterogeneous tissue. In this technique, a transparent thermoplastic film (ethylene vinyl acetate polymer) is applied to the surface of the tissue section on a standard glass histopathology slide; a carbon dioxide laser pulse then specifically activates the film above the cells of interest. Strong focal adhesion allows selective procurement of the targeted cells. Multiple examples of LCM transfer and tissue analysis, including polymerase chain reaction amplification of DNA and RNA, and enzyme recovery from transferred tissue are demonstrated.
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                Author and article information

                Contributors
                Journal
                Fertil Steril
                Fertil. Steril
                Fertility and Sterility
                Elsevier for the American Society for Reproductive Medicine
                0015-0282
                1556-5653
                1 November 2014
                November 2014
                : 102
                : 5
                : 1244-1253
                Affiliations
                [a ]Organ Systems, Department of Development and Regeneration, KU Leuven, Leuven, Belgium
                [b ]Department of Obstetrics and Gynecology, Leuven University Fertility Center, University Hospital Leuven, Leuven, Belgium
                [c ]Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
                [d ]Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
                [e ]Boston Center for Endometriosis, Boston Children's Hospital and Brigham and Women's Hospital, Boston, Massachusetts
                [f ]Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milano, Italy
                [g ]University of California San Francisco, San Francisco, California
                [h ]World Endometriosis Research Foundation (WERF), London, United Kingdom
                [i ]Palo Alto Medical Foundation Fertility Physicians of Northern California, Palo Alto, California
                [j ]Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, United Kingdom
                [k ]Endometriosis Care Centre Oxford, University of Oxford, Oxford, United Kingdom
                [l ]Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
                [m ]Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
                Author notes
                []Reprint requests: Krina T. Zondervan, D.Phil., Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, Roosevelt Drive, Oxford OX3 9DU, United Kingdom. krinaz@ 123456well.ox.ac.uk
                Article
                S0015-0282(14)01836-6
                10.1016/j.fertnstert.2014.07.1209
                4230778
                25256928
                fd52b412-9b43-40b5-ae40-b0e07e9f0171
                © 2014 The Authors
                History
                : 23 April 2014
                : 9 July 2014
                : 9 July 2014
                Categories
                Views and Reviews

                Obstetrics & Gynecology
                endometriosis,standardization,standard operating procedures,tissue,ephect
                Obstetrics & Gynecology
                endometriosis, standardization, standard operating procedures, tissue, ephect

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