The behavior of endometrial hyperplasia: A long-term study of “untreated” hyperplasia in 170 patients

Kurman, Robert J.; Kaminski, Paul F.; Norris, Henry J.

doi:10.1016/0090-8258(85)90152-0

Cited by 65 publications

(90 citation statements)

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“…Standard management of postmenopausal AH is hysterectomy because not only is there a risk of coexisting EC, but also the risk of progression to EC over 10 years is around 20%. [32][33][34] With rising rates of AH observed among young women, there is a need for fertility sparing treatment. Weight loss is associated with a reduced risk of EC in epidemiological studies 35,36 and our results demonstrate for the first time that bariatric surgery is capable of not only reversing AH but also sustaining normal morphology.…”

Section: Discussionmentioning

confidence: 99%

The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk

MacKintosh

Derbyshire

McVey

et al. 2018

Intl Journal of Cancer

102

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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‐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/m 2 , 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.

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Section: Discussionmentioning

confidence: 99%

The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk

MacKintosh

Derbyshire

McVey

et al. 2018

Intl Journal of Cancer

102

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“…The relationship between claudins expression and cancer initiation or progression is unclear. Atypical endometrial hyperplasia is thought to be a precursor of EEC, with the potential to progress to invasive endometrial cancer in approximately 29% of cases (16) . Surveillance of hyperplastic endometrium is presently limited by the inability to predict which is at risk of progression.…”

Section: Discussionmentioning

confidence: 99%

Expression of claudin-3 and claudin-4 in normal, hyperplastic, and malignant endometrial tissue

Pan

Wang

Chi

et al. 2007

Int J Gynecol Cancer

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To clarify the roles of claudins in endometrial tumorigenesis, we determined levels of protein and messengerRNA (mRNA) expression of claudin-3 and claudin-4 in human endometrial tissue (proliferative phase [PE, n= 25]; secretory phase [SE, n= 25]; simple hyperplasia [SH, n= 20]; complex hyperplasia [CH, n= 12]; atypical hyperplasia [AH, n= 15]; endometrioid adenocarcinoma [EEC, n= 30]) using immunohistochemistry, western blotting, and real-time polymerase chain reaction, respectively. Morphologic changes of tight junctions (TJs) were also observed in normal, hyperplastic, and malignant endometrial tissue. Absence or weak staining for claudin-3 and claudin-4 was observed in PE, SE, SH, and CH, while medium to intense staining was detected in AH and EEC. Staining of claudin-3 and claudin-4 was predominantly localized to the glandular epithelial cell membrane. Expression of claudin-3 and claudin-4 was significantly increased in the groups of AH and EEC in comparison with the groups of CH, SH, and normal cyclic endometrium at both protein and mRNA levels. The highest expression was observed in EEC. Although no relevance was found with regard to FIGO stage and histologic grade, overexpression of claudin-3 and claudin-4, especially claudin-4, significantly correlated with myometrial invasion. Transmission electron microscopy analysis indicated morphologic disruptions of TJs may lag behind the increase of claudins expression. These results demonstrate that claudin-3 and claudin-4 are strongly expressed in AH and EEC, but less frequently in normal endometrium. The upregulation of claudins expression during endometrial carcinogenesis suggests their potential utility as diagnostic and prognostic biomarkers.

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“…7 It is well known that less than 2% of endometrial hyperplasias without cytological atypia and 23% of hyperplasias with cytological atypia progress to carcinoma if left untreated. 8 Furthermore, the incidence of carcinoma arising in a polyp is thought to be less than 1% and the prognosis in these cases is excellent. However, it would seem prudent to remove all polyps and examine them carefully as well as to scrutinize the hyperplastic endometrium in postmenopausal women with abnormal uterine bleeding.…”

Section: Discussionmentioning

confidence: 99%

Endometrial resection: a diagnostic tool in postmenopausal women

Franchini

Cianferoni

1999

Gynaecol Endoscopy

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Objective To determine the diagnostic role of hysteroscopic endometrial resection in symptomatic postmenopausal women. Design Retrospective study. Setting Gynaecology department at a general hospital. Patients 150 postmenopausal women with abnormal uterine bleeding. Interventions Hysteroscopic transcervical resection of endometrium under general or spinal anaesthesia. Results Eight endometrial carcinomas were detected in endometrial chips and were managed with simple hysterectomy. A benign organic cause was noted in 131 cases, and 11 women had atrophic endometrium. All 142 postmenopausal women with a benign lesion were satisfied with their treatment and had no recurrence of abnormal bleeding during a mean follow up of 28 months. Conclusion Endometrial transcervical resection is a reasonable clinical strategy for single‐procedure evaluation and treatment in postmenopausal women with abnormal uterine bleeding.

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The behavior of endometrial hyperplasia: A long-term study of “untreated” hyperplasia in 170 patients

Cited by 65 publications

References 0 publications

The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk

The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk

Expression of claudin-3 and claudin-4 in normal, hyperplastic, and malignant endometrial tissue

Endometrial resection: a diagnostic tool in postmenopausal women

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