Skip to main content
Download PDF

Risk factors of endometrial cancer in patients with endometrial hyperplasia: implication for clinical treatments

BMC Women's Health volume 21, Article number: 312 (2021) Cite this article

Abstract

Background

Endometrial hyperplasia (EH) is commonly-seen in the patients with endometrial cancer (EC), we aimed to evaluated the risk factors of EC in patients with EH, to provide evidence to the clinical prevention and treatment of EC.

Methods

This study was a retrospective study design. EH patients confirmed by pathological examinations and treated with hysterectomy in our hospital from June 1, 2018 to February 28, 2021 were included. The clinical characteristics of EC and no-EC patients were compared and analyzed. Logistics regression analyses were conducted to evaluate the risk factors of EC in patients with EH.

Results

A total of 228 EH patients were included, the incidence of EC in the EH patients was 31.58%. There were significant differences in the age, BMI, diabetes, hypertension and pathology of EH between EC and no EC groups (all P < 0.05), no significant differences in the hyperlipidemia, preoperative CA125, number of deliveries, menopause and endometrial thickness between EC and no EC groups were found (all P > 0.05). Logistic regression analyses indicated that age > 50 y (OR 3.064, 95% CI 1.945–5.931), BMI ≥ 25 kg/m2 (OR 2.705, 95% CI 1.121–3.889), diabetes (OR 3.049, 95% CI 1.781–5.114), hypertension (OR 2.725, 95% CI 1.108–3.431) and severe hyperplasia (OR 3.181, 95% CI 1.496–4.228) were the risk factors of EC in patients with EH (all P < 0.05).

Conclusions

The risk of EC in EH patients is high, especially for those patients with age > 50 y, BMI ≥ 25 kg/m2, diabetes, hypertension and severe hyperplasia, special attentions should be paid for occurrence of EC and early diagnosis and early treatment are needed for those patients.

Peer Review reports

Background

Endometrial cancer (EC) is one of the common malignant tumors in gynecology, and its incidence is increasing year by year, and is showing a trend of younger onset age [1]. It is generally believed that the continuous stimulation of estrogen without progesterone antagonism leads to endometrial hyperplasia and then cancerous transformation [2, 3]. Endometrial hyperplasia (EH) is a common gynecological endocrine disease, which mainly manifests as irregular vaginal bleeding, infertility, and even malignant transformation [4]. Endometrial dysplasia has certain tendency to become cancerous, and it is recognized as a precancerous lesion of EC with incidence of 23.15–29.08% [5, 6]. Therefore, early detection and intervention of EH is of great significance to improve the prognosis of patients.

Previous studies [7, 8] have shown that it’s very common that EH and EC can coexist in patients. The risk of endometrial dysplasia combined with endometrial cancer is as high as 25.76 to 59.22% [9, 10]. Clinically, there is a certain missed diagnosis rate in the diagnosis of EC [11]. How to identify high-risk patients with EC from patients with EH, is important to guide clinical treatment decisions and improve the prognosis of patients. Therefore, this present study analyzed the clinicopathological data of patients diagnosed with EH before hysterectomy, aimed to explore the high-risk factors of EC in patients with EH, to provide evidence support to the early prevention and clinical treatment of EC.

Methods

Ethics

This study was a retrospective study design. In this study, all methods were conducted in comply with the relevant guidelines and regulations. This present study had been verified and approved by the ethical committee of our hospital (approval number: MD10180068-2c), and written informed consents had been obtained from all the included patients.

Patients

We selected EH patients treated with hysterectomy in our hospital from June 1, 2018 to February 28, 2021 as the study populations. The criterial for patient inclusion were: the endometrial thickness was determined by the B-ultrasound (endometrial thickness ≥ 4 mm) and pathological examinations, the ultrasound examinations of all selected patients were performed by the same group of sonographers in our hospital; patients underwent hysterectomy treatment in our hospital, and there were complete postoperative pathological reports; there was no history of hormone replacement therapy in the past 1 year. All consecutive patients meeting the selection criteria were included. Patients who did not agree to participant in this study and did not sign the inform consents were excluded.

Data collection

We collected personal and treatment information of patients, including age, body mass index (BMI), diabetes, hypertension, hyperlipidemia, preoperative CA125 (U/ml) level, number of deliveries, menopause status, preoperative endometrial thickness, and the final pathological results.

Treatment and follow-up

The diagnosis of EH referred to relevant standards and criteria [12, 13], and EH was divided into mild, moderate, and severe group according to the degree of disease. All patients underwent total hysterectomy in our hospital. According to the final pathological results after total hysterectomy, it was judged whether EC existed at the same time, and the diagnosis of EC referred to relevant standards. If the postoperative pathological examination results suggested that there was EC, further corresponding treatments were conducted. We conducted follow-up till the discharge of patients.

Statistical method

We used SPSS 24.0 software to analyze the data, and the measurement data were expressed as mean ± standard deviation, and the comparison between the two groups used independent sample t test. Categorical variables were expressed as percentages, and Chi-square or Fisher exact probability tests were used for comparison between groups. We used logistic multiple regression analysis to explore high-risk factors related to EC. In this study, the difference was statistically significant with P < 0.05.

Results

Patients

A total of 228 EH patients were included, of whom 72 patients had EC, the incidence of EC in the EH patients was 31.58%. As presented in Table 1, there were significant differences in the age, BMI, diabetes, hypertension and pathology of EH between EC and no EC groups (all P < 0.05), no significant differences in the hyperlipidemia, preoperative CA125, number of deliveries, menopause and endometrial thickness between EC and no EC groups were found (all P > 0.05).

Table 1 The characteristics of included patients
Full size table

Risk factors of EC in patients with EH

The variable assignments of multivariate logistic regression were presented in Table 2. As indicated in Table 3, logistic regression analyses indicated that age > 50 y (OR 3.064, 95% CI 1.945–5.931), BMI ≥ 25 kg/m2 (OR 2.705, 95% CI 1.121–3.889), diabetes (OR 3.049, 95% CI 1.781–5.114), hypertension (OR 2.725, 95% CI 1.108–3.431) and severe hyperplasia (OR 3.181, 95% CI 1.496–4.228) were the risk factors of EC in patients with EH (all P < 0.05).

Table 2 The variable assignment of multivariate logistic regression
Full size table
Table 3 The logistic regression analysis on the risk factors of endometrial cancer in patients with endometrial hyperplasia
Full size table

Discussions

The results of this present study have found that the incidence of EC in the EH patients was 31.58%, which is similar to previous reports [14, 15]. Besides, we have found that for patients with age > 50 y, BMI ≥ 25 kg/m2, diabetes, hypertension and severe hyperplasia, they may have higher risks of EC in patients with EH, early targeted preventions and interventions are needed for patients with those factors. The increase in estrogen levels in the body caused by various reasons continuously stimulates the proliferation of endometrial tissue [16]. The proliferated endometrial tissue is stimulated by a single estrogen for a long time without progesterone antagonism, which is likely to cause excessive endometrial cell proliferation [17]. Tumor cells infiltrate local blood vessels or necrosis and disintegration of their own tissues can cause bleeding [18]. The most common pathological type of endometrial cancer is endometrioid adenocarcinoma, which accounts for about 74.25 to 80.11% [19, 20]. Therefore, the early identification and treatment of EC in the EH patients is vital to the prognosis of EH patients.

The main cause is the long-term estrogen exposure of the endometrium and the lack of progesterone antagonism [21]. It is generally believed that endometrial cancer is more likely to occur in perimenopausal women [22]. Studies [23,24,25] have pointed out that age is a high-risk factor for endometrial dysplasia coexisting with EC. Previous study [26] has reported that endometrial hyperplasia patients aged 40–59 have an increased risk of endometrial cancer (OR 3.07, 95% CI 1.18–7.97); The risk is higher when the age is ≥ 60 (DR 6.65, 95% CI 1.75–25.3). The potential reasons may be that due to the perimenopausal age at which EC is likely to occur, which is related to the decline of the body's immune function [27]. It’s been reported that the incidence of EC under the age of 50 is 102 per 100,000, while the incidence of EC over the age of 50 has risen to 1374 per 100,000 [28]. The older the age, the more severe the disease and the lower the survival rate [29]. The results of this study also suggest that age ≥ 50 years old is a high-risk factor for the development of EC. Therefore, for the elderly, especially those with EH aged ≥ 48 years, they need to be treated with caution in clinical practice.

The pathological change of EH must be considered in the diseases progress. Among endometrial diseases, EH is the most common benign disease, and EC is one of the most common female reproductive system tumors, accounting for 20 to 30% of female reproductive tract malignant tumors [30]. In the past 20 years, the incidence of endometrial cancer has shown an obvious upward trend [31]. It is generally believed that endometrial lesions are a process in which the lesions continue to progress, that is, from not accompanied by EH to accompanied by EH, and finally progressing to well-differentiated EC [32, 33]. However, some scholars [21, 34] have reported that the incidence of EC in patients with endometrial hyperplasia is 12.18–46.34%. The results of this study also suggest that severe EH is also a high-risk factor for EC. However, the clinical reason for the failure to find coexisting EC before surgery may be that the preoperative endometrial sampling is mainly by diagnosing curettage, AEH lesions may be single or scattered lesions, which are affected by the experience of the surgeon, and there is a possibility of missed curettage [35, 36]. In addition, the diagnosis of well-differentiated EC is mainly based on the presence or absence of endometrial stroma, but it is sometimes difficult to determine [37]. This study has found that the risk of patients with endometrial cancer increase significantly with the severity of EH. Therefore, for patients whose endometrial biopsy pathology is severe EH, due to the high probability of EC, early alerts of EC are needed for those patients.

Several high-risk factors for EC should be concerned and get the attentions of clinical health workers. Studies [38, 39] have pointed out that obesity and diabetes are high-risk factors for EC. For every 5 kg/m2 increase in BMI, the risk of EC increases 1.6 times. Several studies [40, 41] have also shown that obesity in patients with endometrial cancer also increases the risk of endometrial cancer-related deaths. The reason is that adipose tissue is the source of estrogen in the body. Obesity causes excessive endogenous estrogen to act on the endometrium, leading to EH and EC. Studies [3, 42, 43] have shown that when the insulin resistance index is greater than or equal to 2.8809, the relative risks of endometrial hyperplasia and endometrial cancer are 35.22 and 30.59, respectively. It’s been found that when BMI ≥ 25 kg/m2, progesterone treatment is less effective and prone to recurrence. Therefore, weight control should be strengthened during treatment and follow-up. Simple hypertension does not increase the occurrence of endometrial cancer, but hypertension patients are often complicated by obesity and diabetes. Therefore, early control of weight, blood sugar and blood pressure are vital to improve the prognosis of patients.

It must be noted that the pathological types of EC with coexisting EH are hormone-dependent EC, more than 90% are well-differentiated cancers, about 40% of the lesions are confined to the endometrium, and about 50% are accompanied by superficial muscle layer infiltration, about 10% is accompanied by deep muscle layer infiltration [44]. Besides, there may be some immunohistochemical factors in predicting EC in EH patients. AT-rich interaction domain 1A (ARID1A) loss in premalignant EH is an accurate and almost perfectly specific prognostic marker for coexistent cancer [45]. Besides, it’s been found that PTEN loss in EH is a risk factor for EC, but is not reliable in predicting the risk of EC [46]. In this present study, four cases underwent lymph node resection after surgery, and the pathological examination results were negative. There was no recurrence or death due to cancer in the follow-up. Previous study [47] have found that after resection of the uterus due to EH are highly differentiated stage I cases, with only 6 cases of moderately differentiated cancer and 2 cases of poorly differentiated cancer.

Conclusions

In conclusion, we have found that the incidence of EC in the EH patients was 31.58%, age > 50 y, BMI ≥ 25 kg/m2, diabetes, hypertension and severe hyperplasia are the independent risk factors of EC in patients with EH. For controllable high-risk factors, such as obesity, diabetes and hypertension, clinical education and intervention should be strengthened with more focus on changes in patients’ lifestyles, and early preventions are needed to reduce the development of EC.

Availability of data and materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

EC:

Endometrial cancer

EH:

Endometrial hyperplasia

BMI:

Body mass index

OR:

Odds ratio

CI:

Confidence interval

References

  1. Vetter MH, Smith B, Benedict J, Hade EM, Bixel K, Copeland LJ, Cohn DE, Fowler JM, O’Malley D, Salani R, et al. Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia. Am J Obstet Gynecol. 2020;222(1):60.e61–60.e67.

    Article  Google Scholar 

  2. Doherty MT, Sanni OB, Coleman HG, Cardwell CR, McCluggage WG, Quinn D, Wylie J, McMenamin UC. Concurrent and future risk of endometrial cancer in women with endometrial hyperplasia: a systematic review and meta-analysis. PLoS ONE. 2020;15(4):e0232231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Jordan SJ, Na R, Weiderpass E, Adami HO, Anderson KE, van den Brandt PA, Brinton LA, Chen C, Cook LS, Doherty JA, et al. Pregnancy outcomes and risk of endometrial cancer: a pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium. Int J Cancer. 2021;148(9):2068–78.

    Article  CAS  PubMed  Google Scholar 

  4. Clarke MA, Long BJ, Sherman ME, Lemens MA, Podratz KC, Hopkins MR, Ahlberg LJ, Mc Guire LJ, Laughlin-Tommaso SK, Bakkum-Gamez JN, et al. Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms. Am J Obstet Gynecol. 2020;223(4):549.e541–549.e513.

    Article  Google Scholar 

  5. Padilla-Iserte P, Lago V, Tauste C, Diaz-Feijoo B, Gil-Moreno A, Oliver R, Coronado P, Martin-Salamanca MB, Pantoja-Garrido M, Marcos-Sanmartin J, et al. Impact of uterine manipulator on oncological outcome in endometrial cancer surgery. Am J Obstet Gynecol. 2021;224(1):65.e61–65.e11.

    Article  Google Scholar 

  6. Kim S, Park J, Chen Y, Rowe K, Snyder J, Fraser A, Smith K, Deshmukh VG, Newman M, Herget K, et al. Long-term diabetes risk among endometrial cancer survivors in a population-based cohort study. Gynecol Oncol. 2020;156(1):185–93.

    Article  PubMed  Google Scholar 

  7. Saleh M, Virarkar M, Bhosale P, El Sherif S, Javadi S, Faria SC. Endometrial cancer, the Current International Federation of Gynecology and Obstetrics Staging System, and the Role of Imaging. J Comput Assist Tomogr. 2020;44(5):714–29.

    Article  PubMed  Google Scholar 

  8. Jeon J, Kim SE, Lee DY, Choi D. Factors associated with endometrial pathology during tamoxifen therapy in women with breast cancer: a retrospective analysis of 821 biopsies. Breast Cancer Res Treat. 2020;179(1):125–30.

    Article  CAS  PubMed  Google Scholar 

  9. Yang BY, Gulinazi Y, Du Y, Ning CC, Cheng YL, Shan WW, Luo XZ, Zhang HW, Zhu Q, Ma FH, et al. Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer: a randomised controlled trial. BJOG. 2020;127(7):848–57.

    Article  PubMed  Google Scholar 

  10. Kokts-Porietis RL, McNeil J, Nelson G, Courneya KS, Cook LS, Friedenreich CM. Prospective cohort study of metabolic syndrome and endometrial cancer survival. Gynecol Oncol. 2020;158(3):727–33.

    Article  PubMed  Google Scholar 

  11. Reinholdt K, Kjaer SK, Guleria S, Frederiksen K, Mellemkjaer L, Munk C, Jensen A. Risk of endometrial cancer among women with benign ovarian tumors—a Danish nationwide cohort study. Gynecol Oncol. 2020;157(2):549–54.

    Article  CAS  PubMed  Google Scholar 

  12. Juan L, Jinghe L, Lina G, Qiaozhi L. Gynecological oncology. Beijing: People’s Medical Publishing House; 2016.

    Google Scholar 

  13. Association FRDGoPBoCM. Pathological diagnosis criteria for endometrial cancer. Chin J Pathol. 2020;49(3):214–9.

    Google Scholar 

  14. Shen L, Wu Y, Li A, Li L, Shen L, Jiang Q, Li Q, Wu Z, Yu L, Zhang X. LncRNA TTNAS1 promotes endometrial cancer by sponging miR376a3p. Oncol Rep. 2020;44(4):1343–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Giannella L, Delli Carpini G, Sopracordevole F, Papiccio M, Serri M, Giorda G, Tsiroglou D, Del Fabro A, Ciavattini A. Atypical endometrial hyperplasia and unexpected cancers at final histology: a study on endometrial sampling methods and risk factors. Diagnostics (Basel). 2020;10(7):474.

    Article  Google Scholar 

  16. Matsuo K, Ramzan AA, Gualtieri MR, Mhawech-Fauceglia P, Machida H, Moeini A, Dancz CE, Ueda Y, Roman LD. Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia. Gynecol Oncol. 2015;139(2):261–7.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rakha E, Wong SC, Soomro I, Chaudry Z, Sharma A, Deen S, Chan S, Abu J, Nunns D, Williamson K, et al. Clinical outcome of atypical endometrial hyperplasia diagnosed on an endometrial biopsy: institutional experience and review of literature. Am J Surg Pathol. 2012;36(11):1683–90.

    Article  PubMed  Google Scholar 

  18. Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, Xiang YB, Wolk A, Wentzensen N, Weiss NS, Webb PM, et al. Type I and II endometrial cancers: have they different risk factors? J Clin Oncol. 2013;31(20):2607–18.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Matsuo K, Mandelbaum RS, Ciccone M, Khoshchehreh M, Pursuwani H, Morocco EB, Matsuzaki S, Dancz CE, Ozel B, Paulson RJ, et al. Route-specific association of progestin therapy and concurrent metformin use in obese women with complex atypical hyperplasia. Int J Gynecol Cancer. 2020;30(9):1331–9.

    PubMed  PubMed Central  Google Scholar 

  20. Hutt S, Tailor A, Ellis P, Michael A, Butler-Manuel S, Chatterjee J. The role of biomarkers in endometrial cancer and hyperplasia: a literature review. Acta Oncol. 2019;58(3):342–52.

    Article  PubMed  Google Scholar 

  21. Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: the diagnosis of endometrial hyperplasia. Hum Reprod Update. 2017;23(2):232–54.

    PubMed  Google Scholar 

  22. Travaglino A, Raffone A, Saccone G, Mollo A, De Placido G, Insabato L, Zullo F. Endometrial hyperplasia and the risk of coexistent cancer: WHO versus EIN criteria. Histopathology. 2019;74(5):676–87.

    Article  PubMed  Google Scholar 

  23. Pal N, Broaddus RR, Urbauer DL, Balakrishnan N, Milbourne A, Schmeler KM, Meyer LA, Soliman PT, Lu KH, Ramirez PT, et al. Treatment of low-risk endometrial cancer and complex atypical hyperplasia with the levonorgestrel-releasing intrauterine device. Obstet Gynecol. 2018;131(1):109–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Alcazar JL, Bonilla L, Marucco J, Padilla AI, Chacon E, Manzour N, Salas A. Risk of endometrial cancer and endometrial hyperplasia with atypia in asymptomatic postmenopausal women with endometrial thickness ≥ 11 mm: a systematic review and meta-analysis. J Clin Ultrasound. 2018;46(9):565–70.

    Article  PubMed  Google Scholar 

  25. Rosen MW, Tasset J, Kobernik EK, Smith YR, Johnston C, Quint EH. Risk factors for endometrial cancer or hyperplasia in adolescents and women 25 years old or younger. J Pediatr Adolesc Gynecol. 2019;32(5):546–9.

    Article  PubMed  Google Scholar 

  26. Trimble CL, Kauderer J, Zaino R, Silverberg S, Lim PC, Burke JJ 2nd, Alberts D, Curtin J. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer. 2006;106(4):812–9.

    Article  PubMed  Google Scholar 

  27. Mutter GL, Kauderer J, Baak JP, Alberts D, Gynecologic Oncology G. Biopsy histomorphometry predicts uterine myoinvasion by endometrial carcinoma: a Gynecologic Oncology Group study. Hum Pathol. 2008;39(6):866–74.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Ying Z, Fengzhi F, Ying J. High-risk factors and prognosis analysis of endometrial hyperplasia complicated with endometrial cancer. J Pract Obstet Gynecol. 2016;32(11):826–9.

    Google Scholar 

  29. Travaglino A, Raffone A, Saccone G, Insabato L, Mollo A, De Placido G, Zullo F. Immunohistochemical predictive markers of response to conservative treatment of endometrial hyperplasia and early endometrial cancer: a systematic review. Acta Obstet Gynecol Scand. 2019;98(9):1086–99.

    Article  CAS  PubMed  Google Scholar 

  30. Harrison RF, He W, Fu S, Zhao H, Sun CC, Suidan RS, Woodard TL, Rauh-Hain JA, Westin SN, Giordano SH, et al. National patterns of care and fertility outcomes for reproductive-aged women with endometrial cancer or atypical hyperplasia. Am J Obstet Gynecol. 2019;221(5):474.e471–474.e411.

    Article  CAS  Google Scholar 

  31. Pennant ME, Mehta R, Moody P, Hackett G, Prentice A, Sharp SJ, Lakshman R. Premenopausal abnormal uterine bleeding and risk of endometrial cancer. BJOG. 2017;124(3):404–11.

    Article  CAS  PubMed  Google Scholar 

  32. Yang B, Xu Y, Zhu Q, Xie L, Shan W, Ning C, Xie B, Shi Y, Luo X, Zhang H, et al. Treatment efficiency of comprehensive hysteroscopic evaluation and lesion resection combined with progestin therapy in young women with endometrial atypical hyperplasia and endometrial cancer. Gynecol Oncol. 2019;153(1):55–62.

    Article  CAS  PubMed  Google Scholar 

  33. Ceylan Y, Akpinar G, Doger E, Kasap M, Guzel N, Karaosmanoglu K, Kopuk SY, Yucesoy I. Proteomic analysis in endometrial cancer and endometrial hyperplasia tissues by 2D-DIGE technique. J Gynecol Obstet Hum Reprod. 2020;49(2):101652.

    Article  PubMed  Google Scholar 

  34. Travaglino A, Raffone A, Saccone G, Mollo A, De Placido G, Mascolo M, Insabato L, Zullo F. Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia. APMIS. 2019;127(6):427–34.

    Article  PubMed  Google Scholar 

  35. Hahn HS, Chun YK, Kwon YI, Kim TJ, Lee KH, Shim JU, Mok JE, Lim KT. Concurrent endometrial carcinoma following hysterectomy for atypical endometrial hyperplasia. Eur J Obstet Gynecol Reprod Biol. 2010;150(1):80–3.

    Article  PubMed  Google Scholar 

  36. Man GCW, Wang J, Song Y, Wong JH, Zhao Y, Lau TS, Leung KT, Chan TH, Wang H, Kwong J, et al. Therapeutic potential of a novel prodrug of green tea extract in induction of apoptosis via ERK/JNK and Akt signaling pathway in human endometrial cancer. BMC Cancer. 2020;20(1):964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhang G, Chen H, Liu Y, Niu L, Jin L, Li D, Song L, Shang L, Lin X, Wang F, et al. Is lymph node dissection mandatory among early stage endometrial cancer patients? A retrospective study. BMC Womens Health. 2020;20(1):258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Raffone A, Travaglino A, Saccone G, D’Alessandro P, Arduino B, Mascolo M, De Placido G, Insabato L, Zullo F. Diabetes mellitus is associated with occult cancer in endometrial hyperplasia. Pathol Oncol Res. 2020;26(3):1377–84.

    Article  PubMed  Google Scholar 

  39. Travaglino A, Raffone A, Saccone G, D’Alessandro P, Arduino B, de Placido G, Mascolo M, Insabato L, Zullo F. Significant risk of occult cancer in complex non-atypical endometrial hyperplasia. Arch Gynecol Obstet. 2019;300(5):1147–54.

    Article  PubMed  Google Scholar 

  40. Raffone A, Travaglino A, Saccone G, Di Maio A, Mollo A, Mascolo M, De Rosa R, De Placido G, Insabato L, Zullo F. Diabetes mellitus and responsiveness of endometrial hyperplasia and early endometrial cancer to conservative treatment. Gynecol Endocrinol. 2019;35(11):932–7.

    Article  PubMed  Google Scholar 

  41. Garzon S, Uccella S, Zorzato PC, Bosco M, Franchi MP, Student V, Mariani A. Fertility-sparing management for endometrial cancer: review of the literature. Minerva Med. 2021;112(1):55–69.

    Article  PubMed  Google Scholar 

  42. Dashti SG, English DR, Simpson JA, Karahalios A, Moreno-Betancur M, Biessy C, Rinaldi S, Ferrari P, Tjonneland A, Halkjaer J, et al. Adiposity and endometrial cancer risk in postmenopausal women: a sequential causal mediation analysis. Cancer Epidemiol Biomark Prev. 2021;30(1):104–13.

    Article  CAS  Google Scholar 

  43. Hamilton CA, Pothuri B, Arend RC, Backes FJ, Gehrig PA, Soliman PT, Thompson JS, Urban RR, Burke WM. Endometrial cancer: a society of gynecologic oncology evidence-based review and recommendations, part II. Gynecol Oncol. 2021;160(3):827–34.

    Article  PubMed  Google Scholar 

  44. Cordeiro Mitchell CN, Hunkler KF, Maher JY, Garbose RA, Gornet ME, Whiting-Collins LJ, Christianson MS. Conservatively treated endometrial intraepithelial neoplasia/cancer: risk of intrauterine synechiae. J Gynecol Obstet Hum Reprod. 2021;50(5):101930.

    Article  PubMed  Google Scholar 

  45. Raffone A, Travaglino A, Saccone G, Cieri M, Mascolo M, Mollo A, Insabato L, Zullo F. Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer. APMIS. 2019;127(9):597–606.

    Article  CAS  PubMed  Google Scholar 

  46. Raffone A, Travaglino A, Saccone G, Viggiani M, Giampaolino P, Insabato L, Mollo A, De Placido G, Zullo F. PTEN expression in endometrial hyperplasia and risk of cancer: a systematic review and meta-analysis. Arch Gynecol Obstet. 2019;299(6):1511–24.

    Article  CAS  PubMed  Google Scholar 

  47. Guleria S, Jensen A, Albieri V, Nohr B, Frederiksen K, Kjaer SK. Endometrial cancer risk after fertility treatment: a population-based cohort study. Cancer Causes Control. 2021;32(2):181–8.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

None.

Funding

None.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Fuping County Hospital, Weinan, China

    Jie Zhao & Yongting Hu

  2. Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, No. 107 Road Yanjiang West, Guangzhou, China

    Yanan Zhao, Dongmei Chen, Tingfeng Fang & Miao Ding

Authors
  1. Jie Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yongting Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yanan Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongmei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tingfeng Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Miao Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JZ, MD designed research; JZ, YH, YZ, DC, TF, MD conducted research; JZ, YH analyzed data; JZ, MD wrote the first draft of manuscript; MD had primary responsibility for final content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Miao Ding.

Ethics declarations

Ethics approval and consent to participate

In this study, all methods were conducted in comply with the relevant guidelines and regulations. This present study had been verified and approved by the ethical committee of Sun Yat-sen Memorial Hospital of Sun Yat-sen University (approval number: MD10180068-2c), and written informed consents had been obtained from all the included patients.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, J., Hu, Y., Zhao, Y. et al. Risk factors of endometrial cancer in patients with endometrial hyperplasia: implication for clinical treatments. BMC Women's Health 21, 312 (2021). https://doi.org/10.1186/s12905-021-01452-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12905-021-01452-9

Keywords

BMC Women's Health

ISSN: 1472-6874

Contact us