Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis, MN, USA.
Department of Surgery, Park Nicollet Health System, St. Louis Park, MN, USA.
Gynecol Oncol. 2014 Apr;133(1):78-82. doi: 10.1016/j.ygyno.2013.12.005.
Obesity increases risk for endometrial neoplasia, but neither the pathophysiology nor the effects of weight loss on the risk are well established. We attempted to characterize the molecular profile of the endometrium of asymptomatic women with morbid obesity before and following bariatric surgery-induced weight loss.
59 asymptomatic, morbidly obese women underwent endometrial sampling before bariatric surgery; 46 (78%) of these returned one year later for re-biopsy (median weight loss of 41kg). Duplicate samples from these specimens were scored for expression of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), and Ki-67 by two independent, blinded pathologists using an H-score [staining intensity (0-3)×(percent of tissue involved)].
The prevalence of hyperplasia pre-operatively was 7% overall and 10% among patients not on an anti-estrogen. ER H-scores were similar before and after surgery overall (median 190 and 196 respectively, p=0.82), but patients with hyperplasia had higher pre-operative H-scores (median 256, p<0.001) and experienced greater H-score drops, than those without hyperplasia (-112 vs +50, p=0.028). In two patients with persistent hyperplasia at one year, ER H-scores fell to levels that were similar to those without pathology. One patient who developed hyperplasia during the study period had a rising ER H-score. Patients with hyperplasia had higher median PR H-scores pre-operatively (284 vs 188, p=0.01), which normalized through greater drops (75 vs 0, p=0.053). AR H-scores dropped significantly after surgery (13 vs 2, p=0.015), but were similar between patients with and without hyperplasia (p=0.33). Weight loss did not affect Ki-67 proliferation index.
Asymptomatic morbidly obese patients have a high prevalence of occult hyperplasia, characterized by relatively high hormone receptor expression. These profiles appear to normalize with weight loss and in advance of pathologically identifiable changes. These data suggest a potential role for screening this population as well as the possibility that weight loss may be a valid treatment strategy for risk reduction.
肥胖会增加子宫内膜肿瘤的风险,但发病机制和减肥对风险的影响尚不清楚。我们试图描述无症状病态肥胖女性在接受减重手术后子宫内膜的分子特征。
59 名无症状的病态肥胖女性在接受减重手术前进行子宫内膜取样;其中 46 名(78%)一年后返回进行再次活检(中位体重减轻 41kg)。两位独立的、盲法病理学家使用 H 评分(染色强度(0-3)×(组织受累百分比))对来自这些标本的重复样本进行雌激素受体(ER)、孕激素受体(PR)、雄激素受体(AR)和 Ki-67 的表达评分。
术前增生的总患病率为 7%,未服用抗雌激素药物的患者为 10%。总体而言,手术前后 ER H 评分相似(中位数分别为 190 和 196,p=0.82),但增生患者术前 H 评分较高(中位数为 256,p<0.001),且 H 评分下降幅度较大(-112 比+50,p=0.028),而非增生患者则较大。在两名一年后持续增生的患者中,ER H 评分降至无病变水平。在研究期间发生增生的一名患者 ER H 评分升高。增生患者术前 PR H 评分中位数较高(284 比 188,p=0.01),下降幅度较大(75 比 0,p=0.053)。手术后 AR H 评分显著下降(13 比 2,p=0.015),但增生患者与非增生患者之间无差异(p=0.33)。体重减轻并未影响 Ki-67 增殖指数。
无症状病态肥胖患者隐匿性增生的患病率较高,其特征为相对较高的激素受体表达。这些特征似乎随着体重减轻而正常化,并早于病理可识别的变化。这些数据表明对该人群进行筛查可能具有潜在作用,并且体重减轻可能是降低风险的有效治疗策略。