The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk
Renehan, Andrew G
Kitchener, Henry C
Crosbie, Emma J
AffiliationDepartment of Obstetrics and Gynaecology, St Mary's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
MetadataShow full item record
AbstractObesity 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-induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III-IV obesity (body mass index ?40 and ?50 kg/m2 , respectively) immediately prior to gastric bypass or sleeve gastrectomy, and at two and 12 months' follow up. The endometrium underwent pathological examination and immunohistochemistry was used to quantify proliferation (Ki-67), 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-two women underwent bariatric surgery. At 12 months, the mean change in total and excess body weight was -32.7 and -62.8%, 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-67), 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-IR) and inflammation (hsCRP, IL-6), 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-regulation of PI3K-AKT-mTOR signaling with weight loss may have implications for screening, prevention and treatment of this disease.
CitationMacKintosh ML, Derbyshire AE, McVey RJ, Bolton J, Nickkho-Amiry M, Higgins CL, et al. The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk. International Journal of Cancer. 2018 Nov 20.
JournalInt J Cancer
- Women at extreme risk for obesity-related carcinogenesis: Baseline endometrial pathology and impact of bariatric surgery on weight, metabolic profiles and quality of life.
- Authors: Modesitt SC, Hallowell PT, Slack-Davis JK, Michalek RD, Atkins KA, Kelley SL, Arapovic S, Shupnik MA, Hoehn K
- Issue date: 2015 Aug
- Changes in inflammatory endometrial cancer risk biomarkers in individuals undergoing surgical weight loss.
- Authors: Linkov F, Goughnour SL, Ma T, Xu Z, Edwards RP, Lokshin AE, Ramanathan RC, Hamad GG, McCloskey C, Bovbjerg DH
- Issue date: 2017 Oct
- Bariatric surgery-induced weight loss changes immune markers in the endometrium of morbidly obese women.
- Authors: Linkov F, Elishaev E, Gloyeske N, Edwards R, Althouse AD, Geller MA, Svendsen C, Argenta PA
- Issue date: 2014 Sep-Oct
- Hormone receptor expression patterns in the endometrium of asymptomatic morbidly obese women before and after bariatric surgery.
- Authors: Argenta P, Svendsen C, Elishaev E, Gloyeske N, Geller MA, Edwards RP, Linkov F
- Issue date: 2014 Apr
- Obesity surgery and risk of cancer.
- Authors: Mackenzie H, Markar SR, Askari A, Faiz O, Hull M, Purkayastha S, Møller H, Lagergren J
- Issue date: 2018 Nov