{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:50:52Z","timestamp":1787068252703,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,11,20]],"date-time":"2018-11-20T00:00:00Z","timestamp":1542672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["NIHR\u2010CS\u2010012\u2010009"],"award-info":[{"award-number":["NIHR\u2010CS\u2010012\u2010009"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>\n                    Obesity is the strongest risk factor for endometrial cancer (EC). To inform targeted screening and prevention strategies, we assessed the impact of obesity and subsequent bariatric surgery\u2010induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III\u2013IV obesity (body mass index \u226540 and \u226550 kg\/m\n                    <jats:sup>2<\/jats:sup>\n                    , respectively) immediately prior to gastric bypass or sleeve gastrectomy, and at two and 12 months\u2019 follow up. The endometrium underwent pathological examination and immunohistochemistry was used to quantify proliferation (Ki\u201067), oncogenic signaling (PTEN, pAKT, pERK) and hormone receptor (ER, PR) expression status. Circulating biomarkers of insulin resistance, reproductive function and inflammation were also measured at each time point. Seventy\u2010two women underwent bariatric surgery. At 12 months, the mean change in total and excess body weight was \u221232.7 and \u221262.8%, respectively. Baseline endometrial biopsies revealed neoplastic change in 10 women (14%): four had EC, six had atypical hyperplasia (AH). After bariatric surgery, most cases of AH resolved (5\/6) without intervention (3\/6) or with intrauterine progestin (2\/6). Biomarkers of endometrial proliferation (Ki\u201067), oncogenic signaling (pAKT) and hormone receptor status (ER, PR) were significantly reduced, with restoration of glandular PTEN expression, at 2 and 12 months. There were reductions in circulating biomarkers of insulin resistance (HbA1c, HOMA\u2010IR) and inflammation (hsCRP, IL\u20106), and increases in reproductive biomarkers (LH, FSH, SHBG). We found an unexpectedly high prevalence of occult neoplastic changes in the endometrium of women undergoing bariatric surgery. Their spontaneous reversal and accompanying down\u2010regulation of PI3K\u2010AKT\u2013mTOR signaling with weight loss may have implications for screening, prevention and treatment of this disease.\n                  <\/jats:p>","DOI":"10.1002\/ijc.31913","type":"journal-article","created":{"date-parts":[[2018,10,6]],"date-time":"2018-10-06T06:07:48Z","timestamp":1538806068000},"page":"641-650","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk"],"prefix":"10.1002","volume":"144","author":[{"given":"Michelle L.","family":"MacKintosh","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail E.","family":"Derbyshire","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhona J.","family":"McVey","sequence":"additional","affiliation":[{"name":"Department of Histopathology Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Bolton","sequence":"additional","affiliation":[{"name":"Department of Histopathology Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahshid","family":"Nickkho\u2010Amiry","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine L.","family":"Higgins","sequence":"additional","affiliation":[{"name":"Department of Histopathology Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyna","family":"Kamieniorz","sequence":"additional","affiliation":[{"name":"Department of Histopathology Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip W.","family":"Pemberton","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bilal H.","family":"Kirmani","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Liverpool Heart and Chest Hospital  Liverpool United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babur","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Obesity Medicine, Diabetes &amp; Endocrinology Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre  Salford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akheel A.","family":"Syed","sequence":"additional","affiliation":[{"name":"Department of Obesity Medicine, Diabetes &amp; Endocrinology Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre  Salford United Kingdom"},{"name":"Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine &amp; Health University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil J.","family":"Ammori","sequence":"additional","affiliation":[{"name":"Department of Obesity Medicine, Diabetes &amp; Endocrinology Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre  Salford United Kingdom"},{"name":"Division of Diabetes, Endocrinology and Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine &amp; Health University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Renehan","sequence":"additional","affiliation":[{"name":"Obesity and Cancer Research Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health Manchester Cancer Research Centre, NIHR Manchester Biomedical Research Centre, University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry C.","family":"Kitchener","sequence":"additional","affiliation":[{"name":"Gynaecological Oncology Research Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0284-8630","authenticated-orcid":false,"given":"Emma J.","family":"Crosbie","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester United Kingdom"},{"name":"Gynaecological Oncology Research Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,20]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"Uterine cancer statistics [Internet]. 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