European Journal of Gynaecological Oncology,2025,46(9):11-16 DOI:10.22514/ejgo.2025.115
Review
Adenomyosis in endometrial cancer: protective factor or prognostic marker? A narrative review
Vinita Shiwali1, Xintong Cai1, Liping Han1,*,

1Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, 450000 Zhengzhou, Henan, China

*Corresponding Author(s):fcchanlp@zzu.edu.cn (Liping Han)

History Submitted: 25 January 2025 | Accepted: 14 March 2025 | Published: 15 September 2025
Copyright:  ©2025 The Author(s). Published by MRE Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Collapse table of contents

Abstract

The co-occurrence of adenomyosis and endometrial cancer (EC) has garnered increasing attention due to its potential impact on tumor progression and patient outcomes. Adenomyosis, characterized by ectopic endometrial tissue within the myometrium, creates a unique inflammatory and hormonal microenvironment that may influence endometrial tumor biology. This review synthesizes findings from studies conducted in the last decade, focusing on tumor stage, histopathological characteristics, and prognostic outcomes in patients with coexisting adenomyosis and EC. Evidence suggests that adenomyosis is associated with favorable tumor characteristics, such as reduced deep myometrial invasion and lymphovascular space invasion and may correlate with improved survival outcomes. However, conflicting findings highlight the need for further research to elucidate these interactions and their underlying mechanisms.

Keywords:Endometrial cancer;Adenomyosis;Prognostic factors;Disease progression
PDF(304.37 kB)|EndNote (RIS)|BibTeX|RefMan|RefWorks

Cite this article

Vinita Shiwali, Xintong Cai, Liping Han. Adenomyosis in endometrial cancer: protective factor or prognostic marker? A narrative review.European Journal of Gynaecological Oncology,2025,46(9):11-16 DOI:10.22514/ejgo.2025.115

1. Introduction

1.1 Endometrial cancer

Endometrial cancer (EC), the most common gynecological malignancy worldwide and has an increasing incidence due to factors such as obesity, hormonal changes and demographic trends [1, 2]. Although EC predominantly affects postmenopausal women, with 75% of cases occurring in individuals over 50, it is increasingly diagnosed in younger women aged 30–49 due to lifestyle and metabolic factors [3]. In 2020, an estimated 417,367 new cases were reported globally, with the United States alone projecting 66,000 new cases and 13,000 deaths in 2023 [4]. Projections suggest new annual cases in the U.S. may rise to 122,000 by 2030 [2]. Obesity, a modifiable risk factor, accounts for nearly 50% of EC cases and exacerbates risk through chronic estrogen exposure, inflammation, insulin resistance and oxidative stress [5]. Other contributing factors include hormonal imbalances, type2 diabetes mellitus, hypertension, early menarche, late menopause, nulliparity, hormone replacement therapy without progesterone and tamoxifen use, while protective factors include breastfeeding and delayed childbirth [6]. EC is classified into two subtypes: Type I, hormone-driven cancers with favorable outcomes, and Type II, aggressive, poorly differentiated cancers with poor prognosis [7]. Diagnosis relies on transvaginal ultrasound (TVUS), with hysteroscopy-guided biopsy as the gold standard and imaging modalities like Magnetic Resonance Imaging (MRI) and Positron Emission Tomography-Computed Tomography (PET-CT) aiding in staging [6]. Treatment primarily involves total hysterectomy with bilateral salpingo-oophorectomy, with minimally invasive surgery preferred for early-stage disease. Adjuvant therapy is risk-based, ranging from no further treatment for low-risk patients to combined radiotherapy and chemotherapy for high-intermediate-risk patients [4, 8]. Fertility-preserving options, such as progestin-based therapies, are available for young patients with early-stage, low-grade tumors [2].

1.2 Adenomyosis

Adenomyosis is a gynecological disorder where endometrial tissue invades the myometrium, causing uterine enlargement, abnormal uterine bleeding (AUB), pelvic pain and infertility [9]. It can be diffuse or focal, with a prevalence of 12–58% among reproductive-age women [10]. The exact cause is unclear but may involve hormonal imbalances, uterine trauma, or repeated injuries triggering abnormal healing [11]. Risk factors include multiple pregnancies, obesity and surgeries like cesarean sections [12].

Diagnosis has shifted from hysterectomy to non-invasive methods like transvaginal ultrasonography (TVUS) and MRI, with biomarkers like Cancer Antigen (CA)125 aiding in management [13]. Treatment options include hormonal therapies, fertility-sparing surgeries and minimally invasive procedures, while hysterectomy remains definitive for those not preserving fertility [14]. Hysterectomy remains the definitive treatment for women who do not wish to preserve fertility [12].

1.3 The relationship between adenomyosis and endometrial cancer: mechanisms and clinical implications

1.3.1 Adenomyosis as a physical and immunological barrier

Adenomyosis characterized by endometrial tissue invasion into the myometrium, is frequently observed in endometrial cancer (EC) patients [1]. Its fibrotic stroma and altered cytokine profile, including elevated levels of Transforming Growth Factor (TGF)-β and Interleukin (IL)-10, create a microenvironment that suppresses tumor invasion and progression [15, 16]. Additionally, adenomyosis may act as a physical barrier, reducing cancer cell infiltration into the myometrium [17]. The condition’s symptoms such as dysmenorrhea and abnormal bleeding, often lead to earlier detection of EC, facilitating timely diagnosis and intervention [18].

1.3.2 Protective effects on tumor characteristics

Adenomyosis has been associated with less aggressive tumor features in EC, including reduced deep myometrial invasion (DMI), lymphovascular space invasion (LVSI) and lower tumor grades [15]. Patients with adenomyosis are often diagnosed at earlier stages, which correlates with improved overall survival (OS) and disease-free survival (DFS) [4]. However, conflicting evidence exists, necessitating further research to validate these findings [19].

1.3.3 Shared molecular pathways and stem cell dysregulation

Adenomyosis and EC share molecular abnormalities, including dysregulated Wnt/β-catenin signaling, epithelial-mesenchymal transition (EMT) and progesterone resistance [20]. Endometrial stem cell dysfunction is central to both conditions, driving abnormal tissue proliferation and invasion [21]. Mesenchymal stem cells (MSCs) in adenomyosis exhibit altered exosomal miRNA profiles, which may inhibit EMT and metastasis in EC cells, potentially explaining its protective role [22].

1.3.4 Immune modulation and cytokine profiles

Patients with adenomyosis demonstrate an immune microenvironment enriched in antitumor cytokines such as interferon-γ and tumor necrosis factor-α, with reduced pro-tumor cytokines [23, 24]. This immunological shift impairs cancer cell growth and invasion. Additionally, the increased vascular endothelial growth factor (VEGF) levels observed in both conditions contribute to angiogenesis but may also regulate tumor growth differently in adenomyosis-associated EC [25].

1.3.5 Risks of malignant transformation

Adenomyosis carries the rare risk of malignant transformation into endometrial carcinoma arising in adenomyosis (EC-AIA) [19]. This phenomenon is characterized by cancerous changes within adenomyotic tissue, resulting in aggressive tumor behavior and increased metastatic potential [26]. The proximity of adenomyotic tissue to vascular and lymphatic structures may facilitate dissemination, though the exact mechanisms remain unclear [15].

1.3.6 Role of estrogen and annexin A2 in disease progression

Estrogen plays a pivotal role in both adenomyosis and EC by upregulating annexin A2 (ANXA2), a protein involved in EMT and angiogenesis [15]. ANXA2 enhances the invasive properties of adenomyotic and cancerous tissues, correlating with higher International Federation of Gynecology and Obstetrics (FIGO) stages, deeper myometrial invasion and lymph node metastasis in EC [27]. Its contribution to tumor growth and dissemination underscores its significance in the disease’s progression.

1.3.7 Genetic and molecular overlap

Both conditions share genetic mutations in Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) and Protein Phosphatase 2 Regulatory Subunit A Alpha (PPP2R1A), which regulate cell proliferation, survival and invasion [28, 29]. These mutations indicate overlapping pathways in their pathogenesis. Progesterone resistance, common to both, disrupts hormonal balance, allowing uncontrolled proliferation of adenomyotic and cancerous tissues [30].

1.3.8 Oxidative stress and inflammation

Pro-inflammatory cytokines, reactive oxygen species (ROS), and angiogenic factors drive a pro-inflammatory microenvironment in both conditions, promoting tissue damage, repair and proliferation [31, 32]. Oxidative stress and DNA damage further contribute to the progression of adenomyosis and EC [15].

1.4 Review findings

The coexistence of adenomyosis in patients with endometrial cancer (EC) has been a topic of increasing interest, given its potential impact on tumor characteristics and patient outcomes. While some studies report favorable prognostic implications of adenomyosis, others suggest no significant impact on survival or tumor progression. This literature review summarizes findings from systematic reviews, meta-analyses and retrospective studies to provide a comprehensive understanding of this association.

1.4.1 Survival outcomes and meta-analyses

Several studies have investigated the prognostic impact of adenomyosis on survival outcomes in endometrial cancer (EC) patients, yielding mixed results. Raimondo et al. [18] (2021) conducted a systematic review and meta-analysis, reporting that adenomyosis was associated with significantly reduced mortality risks. The pooled hazard ratio (HR) for overall survival (OS) was 0.533 (95% Confidence Interval (CI): 0.329–0.864), and for disease-free survival (DFS), it was 0.536 (95% CI: 0.334–0.859) in univariate analysis. However, these associations were not statistically significant after multivariate adjustment (DFS HR: 0.875, 95% CI: 0.331–2.315). Similarly, Casadio et al. [33] (2021) noted no significant differences in clinical characteristics between EC patients with and without adenomyosis, except for a lower prevalence of nulliparity in the adenomyosis group (pooled Odds Ratio (OR): 0.60, 95% CI: 0.41–0.87, p = 0.007). Contrarily, Buyuksahin et al. [1] (2023) found no significant impact of adenomyosis on OS or DFS, suggesting no effect on overall prognosis.

Boonlak et al. [34] (2019) reported that EC patients without adenomyosis had higher rates of deep myometrial invasion (52.8% vs. 39.4%, p = 0.02) and lymphovascular space invasion (53.2% vs.38.6%, p = 0.01). However, no significant differences were found in five-year OS (HR: 0.81; 95% CI: 0.43–1.53) or recurrence-free survival (HR: 1.47; 95% CI: 0.88–2.44) between the groups.

1.4.2 Potential protective effects

Several studies suggest that adenomyosis may confer a protective effect against aggressive tumor characteristics in EC. Habiba et al. [35] (2018) proposed that the favorable outcomes observed in adenomyosis-associated EC could be attributed to earlier detection. Musa et al. [36] (2012) demonstrated that lymphovascular space invasion (LVSI) predicted lymph node metastasis in EC patients without adenomyosis but not in those with adenomyosis.

Studies by Hertlein et al. [37] (2017) and Gizzo et al. [38] (2016) associated adenomyosis with earlier-stage disease, lower tumor grades and improved five-year survival rates (95% vs. 82%). Wang et al. [39] (2023) reported improved OS (HR: 0.62, 95% CI: 0.50–0.79) and DFS (HR: 0.60, 95% CI: 0.44–0.82) in patients with adenomyosis. Similarly, Matsuo et al. [40] (2014) and Hermens et al. [41] (2022) identified survival benefits, with HRs of 0.42 (95% CI: 0.23–0.78) for OS and 0.25–0.70 for DFS. Celik et al. [42] (2022) found a 52% reduced risk of mortality in patients with adenomyosis (HR: 0.48, 95% CI: 0.29–0.78), while Aslan et al. [43] (2020) observed significantly improved five-year DFS in the adenomyosis group (HR: 0.34, 95% CI: 0.12–0.96). Raffone et al. [44] (2022) further highlighted a protective role for adenomyosis, showing reduced risks of advanced tumor stage (Relative Risk (RR): 0.60, p = 0.005), high tumor grade (RR: 0.55, p < 0.00001) and deep myometrial invasion (RR: 0.65, p = 0.001).

1.4.3 Pathological features

Adenomyosis appears to influence the pathological features of EC. Hirai et al. [45] (1999) reported reduced odds of deep myometrial invasion in adenomyosis patients (OR: 0.37, 95% CI: 0.21–0.65). Zouzoulas et al. [46] (2018) observed a lower likelihood of high-grade tumors in adenomyosis-associated EC, though without statistical significance (OR: 0.57, 95% CI: 0.30–1.07). Zhang et al. [47] (2018) reported that adenomyosis in endometrial cancer patients was linked to earlier-stage disease, lower-grade tumors, and reduced myometrial invasion and lymph node metastasis. It also correlated with improved 5-year survival rates (92.1% vs. 84.1%). Mao et al. [48] (2017) reported that patients with malignant transformation of adenomyosis tended to be younger. Min et al. [49] (2020) through a meta-analysis, concluded that adenomyosis is associated with favorable tumor characteristics, supporting its protective role.

1.4.4 Conflicting evidence

Despite these findings, some studies report conflicting results. Machida et al. [50] (2017) observed an increased HR for reduced DFS (HR: 2.87, 95% CI: 1.44–5.70, p = 0.031) in adenomyosis patients, suggesting more aggressive disease in some cases. Chao et al. [51] (2020) similarly found a higher HR for five-year OS (HR: 3.07, 95% CI: 0.91–10.3), indicating worse outcomes in certain cohorts.

Şimşek et al. [52] (2023) and Yilmaz et al. [53] (2022) found no significant differences in survival or recurrence rates between adenomyosis and non-adenomyosis groups. Yetimalar et al. [54] (2022) noted improved five-year DFS in adenomyosis patients (HR: 0.17, 95% CI: 0.03–1.25), but Taneichi et al. [55] (2014) and Koshiyama et al. [56] (2004) reported only trends favoring survival benefits without statistical significance.

Aydin et al. [57] (2018) observed higher HRs for OS (HR 1.60, 95% CI: 0.49–5.26) and DFS (HR 1.54, 95% CI: 0.56–4.27) in the adenomyosis group, suggesting no survival benefit. Johnatty et al. [58] (2020) described adenomyosis as an independent risk and prognostic factor, but their findings lacked statistical significance for OS (HR 0.77, 95% CI: 0.46–1.28) and DFS (HR 0.52, 95% CI: 0.25–1.07).

2. Summary

Adenomyosis has emerged as a condition of interest in endometrial cancer (EC) research due to its potential association with favorable clinical outcomes. Studies suggest that patients with adenomyosis often experience reduced risks of deep myometrial invasion (DMI), lymphovascular space invasion (LVSI) and high-grade tumors. Moreover, they are frequently diagnosed at earlier stages of EC, which contributes to better overall survival (OS) and disease-free survival (DFS). However, the evidence is not unanimous, with conflicting findings necessitating further investigation to confirm these observations.

The protective role of adenomyosis may be attributed to its unique influence on the tumor microenvironment. The ectopic endometrial glands and stroma embedded within the hypertrophic myometrium are believed to act as a physical barrier, restricting tumor invasion. Furthermore, the inflammatory and hormonal changes characteristic of adenomyosis might suppress tumor progression. Although these mechanisms are intriguing, they remain speculative, requiring additional studies to elucidate their impact on tumor biology.

Adenomyosis frequently coexists with endometriosis in patients with EC, with all three conditions sharing a common foundation in stem cell dysregulation [59]. Abnormal proliferation and differentiation of endometrial and mesenchymal stem cells are thought to drive ectopic tissue growth, chronic inflammation and hormonal imbalances, forming a shared pathological framework [60]. In adenomyosis and endometriosis, these stem cells promote tissue invasion, angiogenesis and immune evasion. Similarly, in EC, stem-like cells are implicated in tumor initiation, metastasis and therapy resistance [61]. This overlapping reliance on stem cell dysfunction offers a plausible explanation for the protective association observed between adenomyosis and EC.

Despite promising insights, research on adenomyosis in EC faces significant limitations and challenges. Variability in diagnostic criteria, small sample sizes, and retrospective study designs hinder the reliability of existing evidence. While meta-analyses have highlighted a possible protective effect, the lack of standardized methodologies and inadequate control for confounding factors complicate the interpretation of findings. These limitations underscore the need for more rigorous and comprehensive investigations.

To advance understanding, future research should prioritize multicenter, prospective studies with larger cohorts and uniform diagnostic criteria. Exploring the biological mechanisms underpinning adenomyosis, particularly its effects on immune modulation and stromal interactions, could provide valuable insights. Furthermore, identifying the precise role of stem cell dysregulation in the pathophysiology of adenomyosis, endometriosis and EC may open avenues for innovative therapeutic strategies.

In conclusion, while adenomyosis shows potential as a protective factor in EC, its role remains incompletely understood. Addressing current research gaps through systematic studies is essential to establish adenomyosis as a reliable prognostic marker and uncover its therapeutic implications. By exploring the interconnected mechanisms of adenomyosis, endometriosis and EC, future work may pave the way for improved patient outcomes and targeted management strategies.

Abbreviations

EC, Endometrial cancer; LVSI, Lymphovascular space invasion; AUB, Abnormal uterine bleeding; DMI, Deep Myometrial Invasion; TVUS, Tras vaginal ultrasound; MRI, Magnatic Resonance Imaging; PET-CT, Positron Emission Tomography-Computed Tomography; CA125, Cancer Antigen 125; KRAS, Kirsten rat sarcoma viral oncogene homolog; MSC, Mesenchymal stem cells; EC-AIA, Endometrial cancer arising-in adenomyosis; ANXA2, Annexin A2; EMT, Epithelial-mesenchymal transition; VEGF, Vascular endothelial growth factor; ROS, Reactive oxygen species; PIK3CA, Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha; OS, Overall Survival; DFS, Disease Free Survival; HR, Hazard Ratio; CI, Confidence Interval; RR, Relative Risk; FIGO, International Federation of Gynecology and Obstetrics; PPP2R1A, Protein Phosphatase 2 Regulatory Subunit A Alpha; OR, Odds Ratio.

Availability of data and materials

This review article is based on a comprehensive analysis of previously published literature. All data and materials used in the preparation of this manuscript are derived from publicly available sources, including published articles, databases, and other referenced materials cited in the manuscript. No new data were generated or analyzed for this study. All relevant references have been included to ensure transparency and reproducibility.

Author contributions

VS—responsible for conceptualization; designed the review framework; conducted the literature search; analysis; interpretation of findings and manuscript writing. XTC—responsible for reviewing and editing. LPH—responsible for supervising and reviewing the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Acknowledgment

Our gratitude to all participants in the study for their invaluable contribution.

Funding

This research was supported by the Natural Science Foundation of Henan Province (242300421278).

Conflict of interest

The authors declare no conflict of interest.

References

Buyuksahin LG, Ibanoglu MC, Ozturk AC, Korkmaz V, Altinbas SK, Engin-Ustun Y. Does coexistence of endometrial cancer and adenomyosis affect survival outcomes? A retrospective cohort study. European Journal of Gynaecological Oncology. 2024; 45: 118–126.

[Google Scholar]

Makker V, MacKay H, Ray-Coquard I, Levine DA, Westin SN, Aoki D, et al. Endometrial cancer. Nature Reviews Disease Primers. 2021; 7: 88.

[Google Scholar]

Markowska A, Chudecka-Głaz A, Pityński K, Baranowski W, Markowska J, Sawicki W. Endometrial cancer management in young women. Cancers. 2022; 14: 1922.

[Google Scholar]

Mahdy H, Vadakekut ES, Crotzer D. Endometrial cancer. StatPearls Publishing: Treasure Island (FL). 2024.

[Google Scholar]

Clontz AD, Gan E, Hursting SD, Bae-Jump VL. Effects of weight loss on key obesity-related biomarkers linked to the risk of endometrial cancer: a systematic review and meta-analysis. Cancers. 2024; 16: 2197.

[Google Scholar]

Bassette E, Ducie JA. Endometrial cancer in reproductive-aged females: etiology and pathogenesis. Biomedicines. 2024; 12: 886.

[Google Scholar]

Saglam O. Uncommon morphologic types of endometrial cancer and their mimickers: how much does molecular classification improve the practice for challenging cases? Life. 2024; 14: 387.

[Google Scholar]

Kalampokas E, Giannis G, Kalampokas T, Papathanasiou AA, Mitsopoulou D, Tsironi E, et al. Current approaches to the management of patients with endometrial cancer. Cancers. 2022; 14: 4500.

[Google Scholar]

Bourdon M, Santulli P, Marcellin L, Maignien C, Maitrot-Mantelet L, Bordonne C, et al. Adenomyosis: an update regarding its diagnosis and clinical features. Journal of Gynecology Obstetrics and Human Reproduction. 2021; 50: 102228.

[Google Scholar]

Selntigia A, Molinaro P, Tartaglia S, Pellicer A, Galliano D, Cozzolino M. Adenomyosis: an update concerning diagnosis, treatment, and fertility. Journal of Clinical Medicine. 2024; 13: 5224.

[Google Scholar]

Khan KN, Fujishita A, Mori T. Pathogenesis of human adenomyosis: current understanding and its association with infertility. Journal of Clinical Medicine. 2022; 11: 4057.

[Google Scholar]

Gunther R, Walker C. Adenomyosis. StatPearls Publishing: Treasure Island (FL). 2024.

[Google Scholar]

Bordonné C, Puntonet J, Maitrot-Mantelet L, Bourdon M, Marcellin L, Dion E, et al. Imaging for evaluation of endometriosis and adenomyosis. Minerva Obstetrics and Gynecology. 2021; 73: 290–303.

[Google Scholar]

Moawad G, Youssef Y, Fruscalzo A, Khedhri S, Faysal H, Pirtea P, et al. Effects of pretreatment strategies on fertility outcomes in patients with adenomyosis. Frontiers in Reproductive Health. 2024; 6: 1484202.

[Google Scholar]

Moraru L, Mitranovici MI, Chiorean DM, Moraru R, Caravia L, Tiron AT, et al. Adenomyosis and its possible malignancy: a review of the literature. Diagnostics. 2023; 13: 1883.

[Google Scholar]

Steen EH, Wang X, Balaji S, Butte MJ, Bollyky PL, Keswani SG. The role of the anti-inflammatory cytokine interleukin-10 in tissue fibrosis. Advances in Wound Care. 2020; 9: 184–198.

[Google Scholar]

Kasius JC, Pijnenborg JMA, Lindemann K, Forsse D, van Zwol J, Kristensen GB, et al. Risk stratification of endometrial cancer patients: FIGO stage, biomarkers and molecular classification. Cancers. 2021; 13: 5848.

[Google Scholar]

Raimondo D, Raffone A, Travaglino A, Maletta M, Casadio P, Ambrosio M, et al. Impact of adenomyosis on the prognosis of patients with endometrial cancer. International Journal of Gynecology & Obstetrics. 2022; 157: 265–270.

[Google Scholar]

Szubert M, Kozirog E, Wilczynski J. Adenomyosis as a risk factor for myometrial or endometrial neoplasms-review. International Journal of Environmental Research and Public Health. 2022; 19: 2294.

[Google Scholar]

Zhang H, Li C, Li W, Xin W, Qin T. Research advances in adenomyosis-related signaling pathways and promising targets. Biomolecules. 2024; 14: 1402.

[Google Scholar]

Hong IS. Endometrial stem cells: orchestrating dynamic regeneration of endometrium and their implications in diverse endometrial disorders. International Journal of Biological Sciences. 2024; 20: 864–879.

[Google Scholar]

Cheng WX, Wei SB, Zhou Y, Shao Y, Li MY. Exosomes: potential diagnostic markers and drug carriers for adenomyosis. Frontiers in Pharmacology. 2023; 14: 1216149.

[Google Scholar]

Ulger G, Gokulu SG, Akay K, Yildiz H, Yildizbakan A, Ilhan TT, et al. Does adenomyosis influence tumor characteristics and survival in endometrioid-type endometrial cancer?? BMC Women’s Health. 2025; 25: 237.

[Google Scholar]

Mitranovici MI, Chiorean DM, Moraru L, Moraru R, Caravia L, Tiron AT, et al. Shared pathogenic and therapeutic characteristics of endometriosis, adenomyosis, and endometrial cancer: a comprehensive literature review. Pharmaceuticals. 2024; 17: 311.

[Google Scholar]

Ghalehbandi S, Yuzugulen J, Pranjol MZI, Pourgholami MH. The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF. European Journal of Pharmacology. 2023; 949: 175586.

[Google Scholar]

Hermens M, van Altena AM, Velthuis I, van de Laar DCM, Bulten J, van Vliet HAAM, et al. Endometrial cancer incidence in endometriosis and adenomyosis. Cancers. 2021; 13: 4592.

[Google Scholar]

Liu F, Liu L, Zheng J. Expression of annexin A2 in adenomyosis and dysmenorrhea. Archives of Gynecology and Obstetrics. 2019; 300: 711–716.

[Google Scholar]

Bulun SE, Yildiz S, Adli M, Wei JJ. Adenomyosis pathogenesis: insights from next-generation sequencing. Human Reproduction Update. 2021; 27: 1086–1097.

[Google Scholar]

Hossain MM, Nakayama K, Shanta K, Razia S, Ishikawa M, Ishibashi T, et al. Establishment of a novel in vitro model of endometriosis with oncogenic KRAS and PIK3CA mutations for understanding the underlying biology and molecular pathogenesis. Cancers. 2021; 13: 3174.

[Google Scholar]

MacLean JA 2nd, Hayashi K. Progesterone actions and resistance in gynecological disorders. Cells. 2022; 11: 647.

[Google Scholar]

Oală IE, Mitranovici MI, Chiorean DM, Irimia T, Crișan AI, Melinte IM, et al. Endometriosis and the role of pro-inflammatory and anti-inflammatory cytokines in pathophysiology: a narrative review of the literature. Diagnostics. 2024; 14: 312.

[Google Scholar]

Yu W, Tu Y, Long Z, Liu J, Kong D, Peng J, et al. Reactive oxygen species bridge the gap between chronic inflammation and tumor development. Oxidative Medicine and Cellular Longevity. 2022; 2022: 2606928.

[Google Scholar]

Casadio P, Raffone A, Maletta M, Travaglino A, Raimondo D, Raimondo I, et al. Clinical characteristics of patients with endometrial cancer and adenomyosis. Cancers. 2021; 13: 4918.

[Google Scholar]

Boonlak S, Aue-Aungkul A, Kietpeerakool C, Kleebkaow P, Chumworathayi B, Luanratanakorn S, et al. Impact of coexisting uterine adenomyosis on the survival outcome of patients with endometrial cancer: a retrospective cohort study. Asian Pacific Journal of Cancer Prevention. 2019; 20: 1185–1190.

[Google Scholar]

Habiba M, Pluchino N, Petignat P, Bianchi P, Brosens IA, Benagiano G. Adenomyosis and endometrial cancer: literature review. Gynecologic and Obstetric Investigation. 2018; 83: 313–328.

[Google Scholar]

Musa F, Frey MK, Im HB, Chekmareva M, Ellenson LH, Holcomb K. Does the presence of adenomyosis and lymphovascular space invasion affect lymph node status in patients with endometrioid adenocarcinoma of the endometrium? American Journal of Obstetrics and Gynecology. 2012; 207: 417.e1–e6.

[Google Scholar]

Hertlein L, Rath J, Zeder-Göss C, Fürst S, Bayer D, Trillsch F, et al. Coexistence of adenomyosis uteri and endometrial cancer is associated with an improved prognosis compared with endometrial cancer only. Oncology Letters. 2017; 14: 3302–3308.

[Google Scholar]

Gizzo S, Patrelli TS, Dall’asta A, DI Gangi S, Giordano G, Migliavacca C, et al. Coexistence of adenomyosis and endometrioid endometrial cancer: role in surgical guidance and prognosis estimation. Oncology Letters. 2016; 11: 1213–1219.

[Google Scholar]

Wang DG, Ji LM, Jia CL, Shao MJ. Effect of coexisting adenomyosis on tumour characteristics and prognosis of endometrial cancer: a systematic review and meta-analysis. Taiwanese Journal of Obstetrics and Gynecology. 2023; 62: 640–650.

[Google Scholar]

Matsuo K, Cahoon SS, Gualtieri M, Scannell CA, Jung CE, Takano T, et al. Significance of adenomyosis on tumor progression and survival outcome of endometrial cancer. Annals of Surgical Oncology. 2014; 21: 4246–4255.

[Google Scholar]

Hermens M, van Altena AM, van der Aa M, Bulten J, van Vliet HAAM, Siebers AG, et al. Endometrial cancer prognosis in women with endometriosis and adenomyosis: a retrospective nationwide cohort study of 40 840 women. International Journal of Cancer. 2022; 150: 1439–1446.

[Google Scholar]

Celik E, Goksever Celik H, Sozen H, Onder S, Tosun OA, Topuz S, et al. The effect of adenomyosis on endometrial cancer: a university hospital-based cohort study. Journal of Obstetrics and Gynaecology. 2022; 42: 158–165.

[Google Scholar]

Aslan K, Sarı ME, Yalçın HR, Yalçın İ, Cüylan ZF, Özdal B. Coexistence of uterine adenomyosis is not associated with a better prognosis in endometrioid-type endometrial cancer. Irish Journal of Medical Science. 2020; 189: 835–842.

[Google Scholar]

Raffone A, Seracchioli R, Raimondo D, Maletta M, Travaglino A, Raimondo I, et al. Prevalence of adenomyosis in endometrial cancer patients: a systematic review and meta-analysis. Archives of Gynecology and Obstetrics. 2021; 303: 47–53.

[Google Scholar]

Hirai M, Hirono M, Oosaki T, Hayashi Y, Yoshihara T, Matsuzaki O. Prognostic factors relating to survival in uterine endometrioid carcinoma. International Journal of Gynecology & Obstetrics. 1999; 66: 155–162.

[Google Scholar]

Zouzoulas OD, Tsolakidis D, Efstratiou I, Pervana S, Pazarli E, Grimbizis G. Correlation between adenomyosis and endometrial cancer: 6-year experience of a single center. Facts, Views and Vision in ObGyn. 2018; 10: 147–152.

[Google Scholar]

Zhang Z, Yang B, Zhang W, Gao X, Zhao C, Zhang X, et al. Clinicopathological characteristics and survival outcomes of patients with coexistence of adenomyosis and endometrial carcinoma. International Journal of Clinical and Experimental Pathology. 2018; 11: 956–962.

[Google Scholar]

Mao X, Zheng W, Mao W. Malignant changes in adenomyosis in patients with endometrial adenocarcinoma: a case series. Medicine. 2017; 96: e8336.

[Google Scholar]

An M, Duan H, Zhang Y. Prognostic significance of co-existent adenomyosis on outcomes and tumor characteristics of endometrial cancer: a meta-analysis. Journal of Obstetrics and Gynaecology Research. 2020; 46: 1851–1863.

[Google Scholar]

Machida H, Maeda M, Cahoon SS, Scannell CA, Garcia-Sayre J, Roman LD, et al. Endometrial cancer arising in adenomyosis versus endometrial cancer coexisting with adenomyosis: are these two different entities? Archives of Gynecology and Obstetrics. 2017; 295: 1459–1468.

[Google Scholar]

Chao X, Wu M, Ma S, Tan X, Zhong S, Bi Y, et al. The clinicopathological characteristics and survival outcomes of endometrial carcinoma coexisting with or arising in adenomyosis: a pilot study. Scientific Reports. 2020; 10: 5984.

[Google Scholar]

Şimşek E, Yıldız Ş, Karakaş S, Gündüz S, Yıldız ÖA, Özdemir İA, et al. Effect of adenomyosis on prognosis of patients with endometrial cancer. Revista da Associação Médica Brasileira. 2023; 69: e20221720.

[Google Scholar]

Yilmaz A, Cokmez H, Gulbahar A. Effect of coexisting adenomyosis on patients with endometrioid adenocarcinoma: determination of intraoperative risk factors for tumor metastasis and estimation of prognosis. Journal of Cancer Research and Therapeutics. 2022; 18: 599–602.

[Google Scholar]

Yetimalar MH, Kilic D, Bezircioglu I, Yigit S. The impact of uterine adenomyosis on the histopathological risk factors and survival in patients with endometrial adenocarcinoma. Journal of Obstetrics and Gynaecology. 2022; 42: 2213–2219.

[Google Scholar]

Taneichi A, Fujiwara H, Takahashi Y, Takei Y, Machida S, Saga Y, et al. Influences of uterine adenomyosis on muscle invasion and prognosis of endometrioid adenocarcinoma. International Journal of Gynecological Cancer. 2014; 24: 1429–1433.

[Google Scholar]

Koshiyama M, Okamoto T, Ueta M. The relationship between endometrial carcinoma and coexistent adenomyosis uteri, endometriosis externa and myoma uteri. Cancer Detection and Prevention. 2004; 28: 94–98.

[Google Scholar]

Aydin HA, Toptas T, Bozkurt S, Pestereli E, Simsek T. Impact of coexistent adenomyosis on outcomes of patients with endometrioid endometrial cancer: a propensity score-matched analysis. Tumori Journal. 2018; 104: 60–65.

[Google Scholar]

Johnatty SE, Stewart CJR, Smith D, Nguyen A, O’Dwyer J, O’Mara TA, et al. Co-existence of leiomyomas, adenomyosis and endometriosis in women with endometrial cancer. Scientific Reports. 2020; 10: 3621.

[Google Scholar]

El Sabeh M, Afrin S, Singh B, Miyashita-Ishiwata M, Borahay M. Uterine stem cells and benign gynecological disorders: role in pathobiology and therapeutic implications. Stem Cell Reviews and Reports. 2021; 17: 803–820.

[Google Scholar]

Laganà AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, et al. The pathogenesis of endometriosis: molecular and cell biology insights. International Journal of Molecular Sciences. 2019; 20: 5615.

[Google Scholar]

Frąszczak K, Barczyński B. Characteristics of cancer stem cells and their potential role in endometrial cancer. Cancers. 2024; 16: 1083.

[Google Scholar]