Molecular classification and clinical significance of endometrial cancer complicated with adenomyosis

Molecular classification and clinical significance of endometrial cancer complicated with adenomyosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Molecular classification and clinical significance of endometrial cancer complicated with adenomyosis Yunan Zhao, Xian Zhang, Xiaguang Shen, Qingquan Zhang, Xuan Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8222275/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Background/Objectives: To study the molecular classification of endometrial cancer combined with adenomyosis and compare its differences in molecular classification and clinicopathological characteristics with endometriosis adenocarcinoma without simultaneous adenomyosis, in order to evaluate the prognosis. Methods: A total of 131 cases of patients with endometrial cancer who underwent initial surgical treatment at Xuanwu Hospital, Capital Medical University from January 1, 2017 to December 31, 2024 were selected for retrospective analysis, Compare the differences in molecular typing and clinicopathological characteristics between 21 cases of endometrial cancer combined with adenomyosis and 110 cases of endometriosis adenocarcinoma without simultaneous adenomyosis. Results: There was no statistically significant difference in molecular typing between endometrial cancer combined with adenomyosis and endometriosis adenocarcinoma without simultaneous adenomyosis ( P=0.398), There were statistically significant differences in the surgical pathological stage and serum CA125 level between the two groups of patients( P<0.05、P=0.029;P<0.05、P=0.005). There were no statistically significant differences between the two groups of patients in terms of height, age, weight, BMI, menopause, vaginal bleeding, uterine cavity space-occupying lesion, vaginal discharge, number of pregnancies, number of deliveries, family history, combined hypertension or diabetes, endometrial thickness, degree of pathological differentiation, LVSI, lesion size and depth of myometrial invasion. No significant differences in general. Conclusion: EC complicated with adenomyosis is an estrogen-dependent tumor, most of which are adenocarcinoma by histopathology. The molecular subtype of EC complicated with adenomyosis is different with endometriosis adenocarcinoma without simultaneous adenomyosis, but the CA125 level is higher and the local invasion ability of the tumor is stronger. endometrial carcinoma adenomyosis Molecular typing Figures Figure 1 1. Introduction Endometrial cancer is a common malignant tumor in gynecology, with endometrioid adenocarcinoma being the most prevalent histological subtype. The 2022 Global Cancer Statistics Report indicates that the incidence of endometrial cancer is rising, ranking sixth among malignant tumors in women[1]. Risk factors include elevated estrogen levels—potentially associated with a high-fat diet, diabetes, and obesity—as well as early menarche, late menopause, nulliparity, advanced age (over 55 years), Lynch syndrome, use of tamoxifen, and hormone replacement therapy[2][3]. In 2013, The Cancer Genome Atlas introduced a four-type molecular classification system for endometrial cancer, replacing the traditional morphology-based classification[4]. Given the associations between endometrial cancer and estrogen exposure, histopathological types, molecular subtypes, and other contributing factors, the diagnosis, treatment, and prognosis of this disease have become increasingly precise and individualized. Adenomyosis is a common benign gynecological condition characterized by the infiltration of endometrial glands and stroma into the myometrium. It is frequently identified during preoperative evaluation or postoperative pathological examination in patients with endometrial cancer[5][6]. The reported prevalence of concurrent adenomyosis in patients with endometrial cancer ranges from 10% to 70%[7]. Although many studies have investigated various aspects of endometrial cancer and adenomyosis, the effect of adenomyosis on the prognosis of endometrial cancer remains unclear. The aim of this study is to compare the molecular subtypes of endometrial carcinoma (EC) complicated with adenomyosis and those of the most common form—endometrioid adenocarcinoma—and to assess differences in clinicopathological features, including medical history, comorbid conditions, tumor markers, and postoperative pathological findings, in order to provide a reference for the clinical management of patients with coexisting EC and adenomyosis. 2. Materials and methods 2.1 Clinical data This retrospective study included 131 patients with endometrial cancer who underwent initial surgical treatment at Xuanwu Hospital of Capital Medical University between January 1, 2017, and December 31, 2024. Among these patients, 21 were diagnosed with endometrial cancer with adenomyosis (EC-A group, 16.03%), and 110 had simple endometrioid adenocarcinoma (EC group, 83.97%). Patients with incomplete staging or who underwent surgery for recurrent disease were excluded. None of the patients received preoperative chemotherapy, radiotherapy, endocrine therapy, or immunotherapy, and there was no history of other malignant tumors. There were no significant differences in age, menopausal status, or body mass index (BMI) between the EC-A group and the EC group (P > 0.05). 2.2 Method High-throughput next-generation sequencing was used to analyze genetic information from 131 resected endometrial cancer samples, including some curettage specimens obtained prior to initial surgery. The gene panel included BRCA1, BRCA2, POLE, and TP53 mutations, as well as microsatellite instability (MSI). Detection involved hybridization with specially designed probes to capture target regions, followed by enrichment through extension, ligation, enzymatic digestion, and amplification. The products were then purified using magnetic beads to construct a sequencing-ready library. Sequencing was conducted on an Illumina platform, and the resulting data were analyzed using proprietary sequencing data analysis software to generate final results. The detected genomic alterations included point mutations, small insertions/deletions (indels), gene fusions, copy number variations, and tumor mutation burden. MSI status was evaluated based on allelic shifts at microsatellite loci, assessed in combination with multiple computational algorithms. Based on the combined evaluation of POLE exonuclease domain mutations, MSI status, and TP53 mutation status, the 131 cases were classified into four molecular subtypes in accordance with the World Health Organization (WHO) Classification of Tumors of Female Reproductive Organs, 5th Edition: POLE-mutated, MMRd (mismatch repair deficient), p53-mutated, and NSMP (no specific molecular profile). Clinicopathological differences between the 21 patients with endometrial carcinoma complicated by adenomyosis and the 110 patients with simple endometrioid adenocarcinoma were compared. Evaluated clinicopathological features included height, age, weight, BMI, menopausal status, vaginal bleeding, uterine cavity space-occupying lesions, vaginal discharge, gravidity, parity, family history, comorbid hypertension or diabetes, serum CA125 levels, endometrial thickness, histological grade, lymphovascular space invasion (LVSI), lesion size, surgical pathological stage, and depth of myometrial invasion. Surgical pathological staging was performed according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria, and tumor grading was based on the 2014 WHO tissue classification. 2.3 Statistical method SPSS version 29.0 was used for statistical analysis. After testing for normality, measurement data conforming to a normal distribution were expressed as mean ± standard deviation, and differences were analyzed using the independent samples t-test. For measurement data not following a normal distribution, results were reported as the median (IQRs), and differences were assessed using the non-parametric rank-sum test. Categorical variables were analyzed using Pearson’s chi-square test. If the expected frequency in any cell was < 5, the continuity correction was applied; if more than 20% of cells in a multi-row or multi-column contingency table had an expected frequency < 5, Fisher’s exact test was used. A P-value < 0.05 was considered statistically significant. The Kaplan–Meier method was used to evaluate the progression-free survival (PFS) between the groups. The groups were also compared using the breslow test. Statistical significance was set as p -values of less than 0.05. 3. Results 3.1 Molecular typing comparison between EC-A group and EC group There was no statistically significant difference in molecular subtype distribution between participants with endometrial cancer complicated by adenomyosis (EC-A group) and those with endometrioid adenocarcinoma of the uterus without concurrent uterine adenomyosis (EC group) (P = 0.398), as shown in Table 1 . Table 1 Comparison of molecular classification distribution between EC-A group and EC group [n(%)] Molecular typing χ 2 p POLE (n = 9) MMRd (n = 31) P53abn (n = 13) NSMP (n = 78) 2.985 0.398 EC-A 3(14.3%) 3(14.3%) 2(9.5%) 13(61.9%) EC 6(5.5%) 28(25.5%) 11(10.0%) 65(59.1%) 3.2 Comparison of clinical and pathological features between EC-A group and EC group There were statistically significant differences in serum CA125 levels and surgical pathological staging between the two groups (P < 0.05; P = 0.005 and P < 0.05; P = 0.029, respectively). The EC-A group showed higher CA125 levels. In terms of surgical staging, a greater proportion of EC group cases were classified as stage II, whereas the EC-A group had a higher proportion of stage IIIA cases (involving the serosa and/or adnexa). The distribution of other stages was similar between the groups. No significant differences were observed in height, age, weight, BMI, menopausal status, vaginal bleeding, uterine cavity space-occupying lesions, vaginal discharge, gravidity, parity, family history, comorbid hypertension or diabetes, endometrial thickness, pathological differentiation, depth of myometrial invasion, LVSI, or lesion size (P > 0.05).See Table 2 and Table 3 . Table 2 Comparison of clinical characteristics distribution between EC-A group and EC group Index EC-A group (n = 21) EC group (n = 110) statistic(t, Z, χ 2 ) p Age 58.71 ± 7.52 59.02 ± 9.98 0.132 0.895 Height 160.57 ± 4.88 160.21 ± 5.47 -0.282 0.778 Weight 66.62 ± 10.65 69.71 ± 12.29 1.075 0.284 BMI 25.82 ± 3.90 27.12 ± 4.42 1.258 0.211 Pregnancy number 2(2) 2(2) -0.477 0.634 Production number 1(0) 1(0) -0.494 0.621 CA125 27.93(27.62) 14.57(12.93) -2.817 0.005 Endometrial thickness 8.00(7.28) 11.60(10.00) -1.758 0.079 Menopause 12(57.1%) 83(75.5%) 2.967 0.085 Hemorrhage 20(95.2%) 99(90.0%) 0.122 0.727 Thickening 12(57.1%) 82(74.5%) 2.635 0.105 Uterine cavity lesion 9(42.9%) 45(40.9%) 0.028 0.868 Vaginal discharge 4(19.0%) 10(9.1%) 0.937 0.333 Family background 3(14.3%) 21(19.3%) 0.054 0.817 Combined with hypertension or diabetes 12(57.1%) 60(55.0%) 0.031 0.859 Table 3 Comparison of the distribution of pathological features between EC-A group and EC group [n(%)] Index EC-A group (n = 21) EC group (n = 110) χ 2 p Surgical pathological stage 13.428 0.029 ⅠA 13(61.9%) 78(70.9%) ⅠB 2(9.5%) 13(11.8%) Ⅱ 0(0.0%) 8(7.3%) ⅢA 4(19.0%) 1(0.9%) ⅢB 0(0.0%) 3(2.7%) ⅢC1 1(4.8%) 3(2.7%) ⅢC2 0(0.0%) 1(0.9%) ⅣA 0(0.0%) 0(0.0%) ⅣB 1(4.8%) 3(2.7%) Tissue Differentiation 1.745 0.418 highly differentiated 8(40.0%) 28(25.7%) moderately differentiated 11(55.0%) 73(67.0%) poorly differentiated 1(5.0%) 8(7.3%) Myometrium infiltration 0.709 0.400 1/2 Muscular layer 7(33.3%) 27(24.5%) Lesion size 1.894 0.169 <2cm 4(20.0%) 39(35.8%) ≥ 2cm 16(80.0%) 70(64.2%) LVSI 0.008 0.931 Yes 4(19.0%) 17(15.5%) No 17(81.0%) 93(84.5%) 3.3 Comparison of survival between EC-A and EC groups Both the EC-A and EC groups had good prognosis, and neither group reached the median survival time. There was no statistically significant difference in PFS between the EC-A and EC groups (P = 0.477) (see Table 4 ). The Kaplan–Meier method was used to plot the survival curves of participants in the two groups without disease progression (see Fig. 1 ). Table 4 Comparison of PFS between EC-A group and EC group [n(%)] Index EC-A group (n = 21) EC group (n = 110) χ2 p Survival 20(95.2%) 105(95.5%) 0.505 0.477 Progression or death 1(4.8%) 5(4.5%) 4. Discussion Clinically, auxiliary examinations and postoperative pathological reports in patients with endometrial cancer often indicate coexisting adenomyosis. However, reported prevalence rates vary significantly across studies. Adenomyosis is defined as the migration of endometrial glands and stroma beyond the basal layer of the endometrium into the myometrium[6]. Although it is a benign condition, adenomyosis exhibits features that resemble malignant behavior and may influence the onset and progression of endometrial cancer. Investigating the association and prognostic relevance of these two conditions is of importance for both individual patient outcomes and public health, as it supports early intervention, timely diagnosis, and effective treatment. Numerous studies have examined the pathogenesis, imaging characteristics, pathological staging, and prognostic implications of adenomyosis and endometrial cancer. However, contradictory conclusions in the literature have created uncertainty for clinical decision-making. Adenomyosis is generally considered an estrogen-dependent benign disorder and is thought to be associated with the development and risk factors of endometrioid adenocarcinoma. The present study aimed to compare the molecular subtypes and clinicopathological features of EC with and without adenomyosis, with the goal of contributing to risk assessment and the development of individualized treatment strategies. In August 2023, FIGO revised the 2009 staging system for endometrial cancer by incorporating pathological type, tissue grade, LVSI, and molecular typing into the staging process to form a new system. However, the 2025 NCCN guidelines still recommend treatment based on the 2009 staging system. Treatment recommendations for these risk factors vary by stage and tumor subtype. Although molecular typing is not included in these recommendations, molecular testing is still strongly advised. This study therefore adopted the 2009 staging system for the research[8][9]. Research found no statistically significant difference in molecular subtype distribution between the EC-A and EC groups (P = 0.398). Both groups were mainly characterized by the NSMP classification. Among the four molecular subtypes of endometrial cancer, NSMP is the most common. NSMP lacks specific molecular characteristics, is typically diagnosed at a low grade and early stage, and has an intermediate prognosis. Because most NSMP tumors are low grade, tumor burden is not high, and estrogen and progesterone receptors are positive, these tumors respond well to hormonal or endocrine therapy. Current studies are conducting stratified research on NSMP classification, especially regarding gene mutations such as CTNNB1, PIK3CA, and ARID1A[10]. The PORTEC-4a study reported that patients with endometrial cancer who have a CTNNB1 mutation and are in the early stages of disease should still undergo vaginal brachytherapy, which has shown significantly greater benefits compared to follow-up observation[11]. However, the proportion of POLE-mutated cases was higher in the EC-A group compared to the EC group (14.3% vs. 5.5%), while the MMRd subtype was more frequent in the EC group than in the EC-A group (25.5% vs. 14.3%). The distribution of other subtypes was similar. No cases with overlapping molecular classifications were identified. POLE-mutated tumors typically occur in younger patients. Despite being associated with high tumor grade and abundant tumor-infiltrating lymphocytes, this subtype is paradoxically linked to favorable prognosis[12][13]. In contrast, MMRd-type endometrial cancers are often associated with lower body mass index, more advanced clinical stage, higher tumor grade, increased rates of deep myometrial invasion and LVSI, and poorer overall and progression-free survival[14]. The tumor mutation burden of POLE mutants and MMRd subtypes is very high, which may trigger anti-tumor immune responses. Immunotherapy can be attempted and may improve prognosis. Notably, the proportion of adenocarcinoma in the EC-A group was 95.24% (20 cases of adenocarcinoma and 1 case of serous carcinoma), which may explain the lack of difference in molecular subtype distribution between the two groups. These findings indicate no significant differences in the fundamental mechanisms and processes of tumor occurrence and development between the EC-A and EC groups, thus presenting similar molecular phenotypes. Serum CA125 levels in the EC-A group were significantly higher than those in the EC group (27.93 vs. 14.57, P < 0.05, P = 0.005). The ectopic endometrial glands and stroma within the myometrium in adenomyosis undergo continuous proliferation and bleeding, which stimulates surrounding tissues to initiate immune and inflammatory responses—one of the primary mechanisms leading to elevated CA125 levels[15]. Therefore, the higher CA125 level in the EC-A group does not indicate a higher tumor burden. During preoperative assessment of tumor markers, the clinical relevance of CA125 alone is limited in cases of endometrial cancer with uterine adenomyosis. Studies have demonstrated that the combination of CA125 with other tumor markers, such as HE4 and CA19-9, provides greater diagnostic value than CA125 alone[16]. A statistically significant difference in surgical pathological staging was also observed between the EC-A and EC groups (P < 0.05, P = 0.029). The surgical pathological stages of both groups were mainly stage I, with stage IA accounting for 61.9% versus 70.9% and stage IB accounting for 9.5% versus 11.8%. The higher proportion of stage II disease observed in the EC group (7.3% vs. 0.0%) may reflect a pattern of tumor extension along the endometrial surface, which differs from the invasion patterns typically seen in the EC-A group. A higher proportion of patients in the EC-A group were classified as stage IIIA(19.0% vs.0.9%), and all such cases showed lesions involving the uterine horn, with some extending to the fallopian tube, ipsilateral ovary, or parametrial tissue. It is hypothesized that adenomyosis may contribute to the breakdown of smooth muscle structure in the myometrium, thereby facilitating deeper infiltration and enhancing the invasion and migration of endometrial cancer lesions[17]. Ismiil et al.[18]reported that the incidence of myometrial invasion in endometrial cancer patients with adenomyosis was significantly higher than in those without adenomyosis. In EC-A patients, irregularities at the endometrial–myometrial junction make it difficult to accurately assess the depth of myometrial invasion. This complexity introduces the possibility of misjudgment during pathological staging. Interestingly, even when pathology suggests deep invasion, the prognosis in these cases may still be favorable[19]. According to some reports, despite greater local invasiveness, EC-A patients tend to have a low rate of distant metastasis and recurrence[20]. This study confirmed no statistically significant difference in PFS between the EC-A and EC groups (P = 0.477). Both groups had good prognosis and did not reach the median survival time. The proportion of participants with PFS in the EC-A and EC groups was 95.2% and 95.5%, respectively. Although some EC-A cases had later pathological stages, PFS was similar to that of the EC group, confirming that deep myometrial invasion in patients with uterine adenomyosis is relatively common but does not worsen prognosis. It is also possible that cancerous lesions may involve adenomyosis within the muscular layer, potentially leading to an upgraded pathological stage. The frequent coexistence of endometrial cancer and adenomyosis may be attributed to a shared same stimulating factor—estrogen[21]. Adenomyosis is also commonly associated with other estrogen-related conditions, including uterine fibroids, endometrial hyperplasia, and endometrial polyps[20]. Results from a large prospective study by Kok et al. demonstrated that the risk of endometrial cancer in patients with adenomyosis was four to five times higher than that in women without adenomyosis, a finding linked to elevated estrogen levels[22]. In addition to estrogen dependence, inflammation, KRAS gene mutations, immune system dysregulation, and epithelial-mesenchymal transition are thought to play significant and overlapping roles in the pathogenesis of both conditions, acting as common risk factors for their development[19]. Therefore, the coexistence of endometrial cancer and adenomyosis should not be considered a rare event. Clinically, the coexistence of endometrial cancer with uterine fibroids is also frequently observed. Some studies have reported that the incidence of adenomyosis in postoperative uterine specimens from patients with endometrial cancer is comparable to that observed in specimens from patients with other gynecological conditions[16]. Endometrial cancer and adenomyosis can coexist within the uterine body either independently, without pathological interaction, or with cancer spreading from the eutopic endometrium into adenomyotic foci—or, more rarely, from ectopic endometrial tissue to the eutopic endometrium[23]. A pathological hallmark of endometrial cancer involving adenomyosis is that the cancerous lesion within adenomyosis is typically surrounded by normal endometrial stroma or glands. One such case was identified in the current study. Malignant transformation of ectopic glandular epithelium in adenomyosis is extremely rare, and diagnosis is particularly challenging when the lesion is contiguous with eutopic endometrium. In a retrospective study by Chao et al.[24], among 2080 patients who underwent surgery for endometrial cancer, only 28 cases were diagnosed as adenomyosis-derived malignancy, yielding an incidence of less than 1%. In these cases, p53 mutations were present in approximately 50% of patients, and the predominant histologic subtype was non-endometrioid carcinoma[25]. The rate of metastasis does not appear to differ between cancers originating in adenomyosis and those arising in the eutopic endometrium. However, disease-free survival is reportedly lower in patients with adenomyosis-derived endometrial cancer, and overall prognosis tends to be poorer[26]. Conversely, some studies have suggested that prognosis is comparable between adenomyosis-induced endometrial cancer and cancer that secondarily involves adenomyotic foci, although the former may present with more extensive myometrial invasion[27]. Immunohistochemical expression of CD10 has been reported to assist in identifying cancers that originate from adenomyotic tissue[18][28]. This 2017 retrospective single-center study found no statistically significant difference in molecular subtype distribution between endometrioid carcinoma with adenomyosis and endometrioid adenocarcinoma without adenomyosis. Survival analysis confirmed no significant difference in PFS between the EC-A and EC groups. These results suggest that prognosis in the EC-A group is comparable to that of the EC group. However, the proportion of participants classified as stage IIIA was significantly higher in the EC-A group compared with the EC group (19% versus 0.9%). This observation may indicate stronger local invasive capacity in tumors associated with adenomyosis, which may lead to higher surgical pathological staging and increased likelihood of requiring postoperative adjuvant therapy. Although the cases included in this study were collected from 2017 to the present, molecular classification of endometrial cancer has only recently become widely used in clinical practice. Most cases still include patients diagnosed in the past few years. The accumulation of additional cases in the future will enable more in-depth research. Declarations Assistance with the study: none. Conflict of Interest Statement: The authors declare no conflict of interest. Data Availability Statement: The data that support the findings of this study are available from the corresponding authors upon reasonable request. Ethics Statement : Ethical approval was obtained from the Xuanwu Hospital of Capital Medical University, The data collection and analysis methods were performed in accordance with relevant guidelines and regulations in accordance with the Declaration of Helsinki. Consent to Participate declaration: Every participant gave consent to participate Funding : There is no potential conflict of interest to disclose. This work was not supported by any funding agency. Author Contribution Author ContributionsYunan Zhao (First Author): Conceptualization, Data Curation, Formal Analysis,Investigation,Methodology, Project administration,Visualization, Writing- Original Draft, WritingReview & Editing;Xian Zhang: Data Curation, Formal Analysis, Investigation,Methodology, Project administration,Supervision, Writing- Review & EditingXiaguang Shen: Data Curation, Formal Analysis, Investigation, Writing- Review & EditingQingquan Zhang: Data Curation, Formal Analysis, Investigation, Writing- Review & EditingXuan Wang: Data Curation, Formal Analysis, Supervision,Writing- Review & EditingPeng Dong: Data Curation, Formal Analysis, Writing- Review & EditingLian e Zhou: Formal Analysis, Investigation, Methodology, Writing- Review & EditingShijun wang (Corresponding Author): Conceptualization, Data Curation, Formal, Analysis, Funding acquisition,Investigation,Methodology, Project administration, Resources, Supervision,Writing- Original Draft, WritingReview & Editing; Acknowledgement The manuscript has been edited to ensure language and grammar accuracy and is error free in these aspects. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8222275","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":557866168,"identity":"2bb2a1a9-1594-4368-b518-de5ad7a3ef1f","order_by":0,"name":"Yunan Zhao","email":"","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yunan","middleName":"","lastName":"Zhao","suffix":""},{"id":557866169,"identity":"4da755d7-9fb5-4a01-b02b-f01f3d651d85","order_by":1,"name":"Xian Zhang","email":"","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xian","middleName":"","lastName":"Zhang","suffix":""},{"id":557866170,"identity":"3a1e3153-e4c8-4a21-9385-22cd3c954bdf","order_by":2,"name":"Xiaguang Shen","email":"","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaguang","middleName":"","lastName":"Shen","suffix":""},{"id":557866171,"identity":"bd7e6aa6-1f47-45a0-8f10-65c217008a75","order_by":3,"name":"Qingquan Zhang","email":"","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qingquan","middleName":"","lastName":"Zhang","suffix":""},{"id":557866174,"identity":"c8aacc31-7e38-4f02-9519-7f4663ee0ec6","order_by":4,"name":"Xuan Wang","email":"","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xuan","middleName":"","lastName":"Wang","suffix":""},{"id":557866175,"identity":"b3b95dc7-8995-4175-8638-99dc48f15ac0","order_by":5,"name":"Peng Dong","email":"","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Peng","middleName":"","lastName":"Dong","suffix":""},{"id":557866176,"identity":"ac4eb8a9-41ee-47b4-a52e-51fe94bc8574","order_by":6,"name":"Lian e Zhou","email":"","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Lian","middleName":"e","lastName":"Zhou","suffix":""},{"id":557866177,"identity":"369ddca6-f5d7-4fe9-b296-dcc1e1da0678","order_by":7,"name":"Shijun Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYHCCxAcJFTZybOzNB4jWkmzw4EyaMR/PsQSitbBJPmw7nDhPIkeBOPUG5w88k0g4k5bexpDDwPCjYhsRWm4kJFsA/ZLbxnD2AGPPmduEtZjdYEi8AbQlt42xL4GZsY0YLecPJEgkth1OZ2PmMSBSy4GEJJCWBDY2YrXYA/1iAHSYYRsPW8JBovwi2X8m8eGPCht5+fmPDz74UUGEFgYGngQ48wAx6oGAnViFo2AUjIJRMGIBAHXTQbpOc92LAAAAAElFTkSuQmCC","orcid":"","institution":"Xuan Wu Hospital of the Capital Medical University","correspondingAuthor":true,"prefix":"","firstName":"Shijun","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2025-11-27 12:53:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8222275/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8222275/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":98181221,"identity":"1a9b680c-d5b4-47e0-8986-22edaf6ca6fa","added_by":"auto","created_at":"2025-12-15 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01:09:19","extension":"xml","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":92026,"visible":true,"origin":"","legend":"","description":"","filename":"8108d862bd204d0ebbdfa64d60825c3d1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8222275/v1/16498477c7b5bd2b4a783ebe.xml"},{"id":98181212,"identity":"e3952cb1-34e9-4b75-885f-1a3dd24e6117","added_by":"auto","created_at":"2025-12-15 01:09:22","extension":"html","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":104991,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8222275/v1/92ab28131a9f6d5b3563cf61.html"},{"id":98181210,"identity":"6fb28b5f-89b7-486a-940f-5b8f908463a1","added_by":"auto","created_at":"2025-12-15 01:09:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":23311,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curve of disease-free survival period for patients in EC-A and EC groups\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8222275/v1/f563eb683323cdc4c24eef6e.png"},{"id":98181313,"identity":"59fefcf6-a358-4b61-b7f2-b36bf8fcd492","added_by":"auto","created_at":"2025-12-15 01:09:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":770003,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8222275/v1/8aebe6cd-cfb6-47f3-8ac2-a2f1a72317fa.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Molecular classification and clinical significance of endometrial cancer complicated with adenomyosis","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eEndometrial cancer is a common malignant tumor in gynecology, with endometrioid adenocarcinoma being the most prevalent histological subtype. The 2022 Global Cancer Statistics Report indicates that the incidence of endometrial cancer is rising, ranking sixth among malignant tumors in women[1]. Risk factors include elevated estrogen levels\u0026mdash;potentially associated with a high-fat diet, diabetes, and obesity\u0026mdash;as well as early menarche, late menopause, nulliparity, advanced age (over 55 years), Lynch syndrome, use of tamoxifen, and hormone replacement therapy[2][3]. In 2013, The Cancer Genome Atlas introduced a four-type molecular classification system for endometrial cancer, replacing the traditional morphology-based classification[4]. Given the associations between endometrial cancer and estrogen exposure, histopathological types, molecular subtypes, and other contributing factors, the diagnosis, treatment, and prognosis of this disease have become increasingly precise and individualized. Adenomyosis is a common benign gynecological condition characterized by the infiltration of endometrial glands and stroma into the myometrium. It is frequently identified during preoperative evaluation or postoperative pathological examination in patients with endometrial cancer[5][6]. The reported prevalence of concurrent adenomyosis in patients with endometrial cancer ranges from 10% to 70%[7]. Although many studies have investigated various aspects of endometrial cancer and adenomyosis, the effect of adenomyosis on the prognosis of endometrial cancer remains unclear. The aim of this study is to compare the molecular subtypes of endometrial carcinoma (EC) complicated with adenomyosis and those of the most common form\u0026mdash;endometrioid adenocarcinoma\u0026mdash;and to assess differences in clinicopathological features, including medical history, comorbid conditions, tumor markers, and postoperative pathological findings, in order to provide a reference for the clinical management of patients with coexisting EC and adenomyosis.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Clinical data\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThis retrospective study included 131 patients with endometrial cancer who underwent initial surgical treatment at Xuanwu Hospital of Capital Medical University between January 1, 2017, and December 31, 2024. Among these patients, 21 were diagnosed with endometrial cancer with adenomyosis (EC-A group, 16.03%), and 110 had simple endometrioid adenocarcinoma (EC group, 83.97%). Patients with incomplete staging or who underwent surgery for recurrent disease were excluded. None of the patients received preoperative chemotherapy, radiotherapy, endocrine therapy, or immunotherapy, and there was no history of other malignant tumors. There were no significant differences in age, menopausal status, or body mass index (BMI) between the EC-A group and the EC group (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Method\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eHigh-throughput next-generation sequencing was used to analyze genetic information from 131 resected endometrial cancer samples, including some curettage specimens obtained prior to initial surgery. The gene panel included BRCA1, BRCA2, POLE, and TP53 mutations, as well as microsatellite instability (MSI). Detection involved hybridization with specially designed probes to capture target regions, followed by enrichment through extension, ligation, enzymatic digestion, and amplification. The products were then purified using magnetic beads to construct a sequencing-ready library. Sequencing was conducted on an Illumina platform, and the resulting data were analyzed using proprietary sequencing data analysis software to generate final results. The detected genomic alterations included point mutations, small insertions/deletions (indels), gene fusions, copy number variations, and tumor mutation burden. MSI status was evaluated based on allelic shifts at microsatellite loci, assessed in combination with multiple computational algorithms. Based on the combined evaluation of POLE exonuclease domain mutations, MSI status, and TP53 mutation status, the 131 cases were classified into four molecular subtypes in accordance with the World Health Organization (WHO) Classification of Tumors of Female Reproductive Organs, 5th Edition: POLE-mutated, MMRd (mismatch repair deficient), p53-mutated, and NSMP (no specific molecular profile).\u003c/p\u003e\u003cp\u003eClinicopathological differences between the 21 patients with endometrial carcinoma complicated by adenomyosis and the 110 patients with simple endometrioid adenocarcinoma were compared. Evaluated clinicopathological features included height, age, weight, BMI, menopausal status, vaginal bleeding, uterine cavity space-occupying lesions, vaginal discharge, gravidity, parity, family history, comorbid hypertension or diabetes, serum CA125 levels, endometrial thickness, histological grade, lymphovascular space invasion (LVSI), lesion size, surgical pathological stage, and depth of myometrial invasion. Surgical pathological staging was performed according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria, and tumor grading was based on the 2014 WHO tissue classification.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Statistical method\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eSPSS version 29.0 was used for statistical analysis. After testing for normality, measurement data conforming to a normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, and differences were analyzed using the independent samples t-test. For measurement data not following a normal distribution, results were reported as the median (IQRs), and differences were assessed using the non-parametric rank-sum test. Categorical variables were analyzed using Pearson\u0026rsquo;s chi-square test. If the expected frequency in any cell was \u0026lt;\u0026thinsp;5, the continuity correction was applied; if more than 20% of cells in a multi-row or multi-column contingency table had an expected frequency\u0026thinsp;\u0026lt;\u0026thinsp;5, Fisher\u0026rsquo;s exact test was used. A P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. The Kaplan\u0026ndash;Meier method was used to evaluate the progression-free survival (PFS) between the groups. The groups were also compared using the breslow test. Statistical significance was set as \u003cem\u003ep\u003c/em\u003e-values of less than 0.05.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Molecular typing comparison between EC-A group and EC group\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThere was no statistically significant difference in molecular subtype distribution between participants with endometrial cancer complicated by adenomyosis (EC-A group) and those with endometrioid adenocarcinoma of the uterus without concurrent uterine adenomyosis (EC group) (P\u0026thinsp;=\u0026thinsp;0.398), as shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of molecular classification distribution between EC-A group and EC group [n(%)]\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e\u003cp\u003eMolecular typing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePOLE\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMMRd\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP53abn\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNSMP\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e2.985\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.398\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEC-A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(14.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(14.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2(9.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13(61.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6(5.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28(25.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11(10.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e65(59.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Comparison of clinical and pathological features between EC-A group and EC group\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eThere were statistically significant differences in serum CA125 levels and surgical pathological staging between the two groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; P\u0026thinsp;=\u0026thinsp;0.005 and P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; P\u0026thinsp;=\u0026thinsp;0.029, respectively). The EC-A group showed higher CA125 levels. In terms of surgical staging, a greater proportion of EC group cases were classified as stage II, whereas the EC-A group had a higher proportion of stage IIIA cases (involving the serosa and/or adnexa). The distribution of other stages was similar between the groups. No significant differences were observed in height, age, weight, BMI, menopausal status, vaginal bleeding, uterine cavity space-occupying lesions, vaginal discharge, gravidity, parity, family history, comorbid hypertension or diabetes, endometrial thickness, pathological differentiation, depth of myometrial invasion, LVSI, or lesion size (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).See Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of clinical characteristics distribution between EC-A group and EC group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEC-A group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEC group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;110)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003estatistic(t, Z, χ\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58.71\u0026thinsp;\u0026plusmn;\u0026thinsp;7.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59.02\u0026thinsp;\u0026plusmn;\u0026thinsp;9.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.132\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.895\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e160.57\u0026thinsp;\u0026plusmn;\u0026thinsp;4.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e160.21\u0026thinsp;\u0026plusmn;\u0026thinsp;5.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.282\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.778\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66.62\u0026thinsp;\u0026plusmn;\u0026thinsp;10.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69.71\u0026thinsp;\u0026plusmn;\u0026thinsp;12.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.075\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.284\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25.82\u0026thinsp;\u0026plusmn;\u0026thinsp;3.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27.12\u0026thinsp;\u0026plusmn;\u0026thinsp;4.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.258\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.211\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePregnancy number\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.477\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.634\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProduction number\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.494\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.621\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCA125\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27.93(27.62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.57(12.93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-2.817\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEndometrial thickness\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.00(7.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.60(10.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-1.758\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.079\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMenopause\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12(57.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e83(75.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.967\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.085\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemorrhage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20(95.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99(90.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.122\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.727\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThickening\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12(57.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e82(74.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.635\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.105\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUterine cavity lesion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(42.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45(40.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.028\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.868\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVaginal discharge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4(19.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10(9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.937\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.333\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFamily background\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3(14.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21(19.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.054\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.817\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined with hypertension or diabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12(57.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60(55.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.859\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of the distribution of pathological features between EC-A group and EC group [n(%)]\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEC-A group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEC group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;110)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgical pathological stage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e13.428\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.029\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅠA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13(61.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e78(70.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅠB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2(9.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e13(11.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅡ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8(7.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅢA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4(19.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1(0.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅢB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3(2.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅢC1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(4.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3(2.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅢC2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1(0.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅣA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0(0.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eⅣB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(4.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3(2.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTissue Differentiation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.745\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.418\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ehighly differentiated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8(40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e28(25.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emoderately differentiated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11(55.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e73(67.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epoorly differentiated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(5.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e8(7.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMyometrium infiltration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.709\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.400\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;1/2 Muscular layer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14(66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e83(75.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;1/2 Muscular layer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7(33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27(24.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLesion size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.894\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.169\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;2cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4(20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e39(35.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;2cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16(80.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e70(64.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLVSI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.931\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4(19.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e17(15.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e17(81.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e93(84.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Comparison of survival between EC-A and EC groups\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eBoth the EC-A and EC groups had good prognosis, and neither group reached the median survival time. There was no statistically significant difference in PFS between the EC-A and EC groups (P\u0026thinsp;=\u0026thinsp;0.477) (see Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The Kaplan\u0026ndash;Meier method was used to plot the survival curves of participants in the two groups without disease progression (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of PFS between EC-A group and EC group [n(%)]\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIndex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEC-A group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEC group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;110)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ2\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurvival\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20(95.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e105(95.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.505\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.477\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProgression or death\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1(4.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5(4.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eClinically, auxiliary examinations and postoperative pathological reports in patients with endometrial cancer often indicate coexisting adenomyosis. However, reported prevalence rates vary significantly across studies. Adenomyosis is defined as the migration of endometrial glands and stroma beyond the basal layer of the endometrium into the myometrium[6]. Although it is a benign condition, adenomyosis exhibits features that resemble malignant behavior and may influence the onset and progression of endometrial cancer. Investigating the association and prognostic relevance of these two conditions is of importance for both individual patient outcomes and public health, as it supports early intervention, timely diagnosis, and effective treatment. Numerous studies have examined the pathogenesis, imaging characteristics, pathological staging, and prognostic implications of adenomyosis and endometrial cancer. However, contradictory conclusions in the literature have created uncertainty for clinical decision-making. Adenomyosis is generally considered an estrogen-dependent benign disorder and is thought to be associated with the development and risk factors of endometrioid adenocarcinoma. The present study aimed to compare the molecular subtypes and clinicopathological features of EC with and without adenomyosis, with the goal of contributing to risk assessment and the development of individualized treatment strategies. In August 2023, FIGO revised the 2009 staging system for endometrial cancer by incorporating pathological type, tissue grade, LVSI, and molecular typing into the staging process to form a new system. However, the 2025 NCCN guidelines still recommend treatment based on the 2009 staging system. Treatment recommendations for these risk factors vary by stage and tumor subtype. Although molecular typing is not included in these recommendations, molecular testing is still strongly advised. This study therefore adopted the 2009 staging system for the research[8][9].\u003c/p\u003e\u003cp\u003eResearch found no statistically significant difference in molecular subtype distribution between the EC-A and EC groups (P\u0026thinsp;=\u0026thinsp;0.398). Both groups were mainly characterized by the NSMP classification. Among the four molecular subtypes of endometrial cancer, NSMP is the most common. NSMP lacks specific molecular characteristics, is typically diagnosed at a low grade and early stage, and has an intermediate prognosis. Because most NSMP tumors are low grade, tumor burden is not high, and estrogen and progesterone receptors are positive, these tumors respond well to hormonal or endocrine therapy. Current studies are conducting stratified research on NSMP classification, especially regarding gene mutations such as CTNNB1, PIK3CA, and ARID1A[10]. The PORTEC-4a study reported that patients with endometrial cancer who have a CTNNB1 mutation and are in the early stages of disease should still undergo vaginal brachytherapy, which has shown significantly greater benefits compared to follow-up observation[11].\u003c/p\u003e\u003cp\u003eHowever, the proportion of POLE-mutated cases was higher in the EC-A group compared to the EC group (14.3% vs. 5.5%), while the MMRd subtype was more frequent in the EC group than in the EC-A group (25.5% vs. 14.3%). The distribution of other subtypes was similar. No cases with overlapping molecular classifications were identified. POLE-mutated tumors typically occur in younger patients. Despite being associated with high tumor grade and abundant tumor-infiltrating lymphocytes, this subtype is paradoxically linked to favorable prognosis[12][13]. In contrast, MMRd-type endometrial cancers are often associated with lower body mass index, more advanced clinical stage, higher tumor grade, increased rates of deep myometrial invasion and LVSI, and poorer overall and progression-free survival[14]. The tumor mutation burden of POLE mutants and MMRd subtypes is very high, which may trigger anti-tumor immune responses. Immunotherapy can be attempted and may improve prognosis. Notably, the proportion of adenocarcinoma in the EC-A group was 95.24% (20 cases of adenocarcinoma and 1 case of serous carcinoma), which may explain the lack of difference in molecular subtype distribution between the two groups. These findings indicate no significant differences in the fundamental mechanisms and processes of tumor occurrence and development between the EC-A and EC groups, thus presenting similar molecular phenotypes.\u003c/p\u003e\u003cp\u003eSerum CA125 levels in the EC-A group were significantly higher than those in the EC group (27.93 vs. 14.57, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, P\u0026thinsp;=\u0026thinsp;0.005). The ectopic endometrial glands and stroma within the myometrium in adenomyosis undergo continuous proliferation and bleeding, which stimulates surrounding tissues to initiate immune and inflammatory responses\u0026mdash;one of the primary mechanisms leading to elevated CA125 levels[15]. Therefore, the higher CA125 level in the EC-A group does not indicate a higher tumor burden. During preoperative assessment of tumor markers, the clinical relevance of CA125 alone is limited in cases of endometrial cancer with uterine adenomyosis. Studies have demonstrated that the combination of CA125 with other tumor markers, such as HE4 and CA19-9, provides greater diagnostic value than CA125 alone[16].\u003c/p\u003e\u003cp\u003eA statistically significant difference in surgical pathological staging was also observed between the EC-A and EC groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, P\u0026thinsp;=\u0026thinsp;0.029). The surgical pathological stages of both groups were mainly stage I, with stage IA accounting for 61.9% versus 70.9% and stage IB accounting for 9.5% versus 11.8%. The higher proportion of stage II disease observed in the EC group (7.3% vs. 0.0%) may reflect a pattern of tumor extension along the endometrial surface, which differs from the invasion patterns typically seen in the EC-A group. A higher proportion of patients in the EC-A group were classified as stage IIIA(19.0% vs.0.9%), and all such cases showed lesions involving the uterine horn, with some extending to the fallopian tube, ipsilateral ovary, or parametrial tissue. It is hypothesized that adenomyosis may contribute to the breakdown of smooth muscle structure in the myometrium, thereby facilitating deeper infiltration and enhancing the invasion and migration of endometrial cancer lesions[17]. Ismiil et al.[18]reported that the incidence of myometrial invasion in endometrial cancer patients with adenomyosis was significantly higher than in those without adenomyosis. In EC-A patients, irregularities at the endometrial\u0026ndash;myometrial junction make it difficult to accurately assess the depth of myometrial invasion. This complexity introduces the possibility of misjudgment during pathological staging. Interestingly, even when pathology suggests deep invasion, the prognosis in these cases may still be favorable[19]. According to some reports, despite greater local invasiveness, EC-A patients tend to have a low rate of distant metastasis and recurrence[20]. This study confirmed no statistically significant difference in PFS between the EC-A and EC groups (P\u0026thinsp;=\u0026thinsp;0.477). Both groups had good prognosis and did not reach the median survival time. The proportion of participants with PFS in the EC-A and EC groups was 95.2% and 95.5%, respectively. Although some EC-A cases had later pathological stages, PFS was similar to that of the EC group, confirming that deep myometrial invasion in patients with uterine adenomyosis is relatively common but does not worsen prognosis. It is also possible that cancerous lesions may involve adenomyosis within the muscular layer, potentially leading to an upgraded pathological stage.\u003c/p\u003e\u003cp\u003eThe frequent coexistence of endometrial cancer and adenomyosis may be attributed to a shared same stimulating factor\u0026mdash;estrogen[21]. Adenomyosis is also commonly associated with other estrogen-related conditions, including uterine fibroids, endometrial hyperplasia, and endometrial polyps[20]. Results from a large prospective study by Kok et al. demonstrated that the risk of endometrial cancer in patients with adenomyosis was four to five times higher than that in women without adenomyosis, a finding linked to elevated estrogen levels[22]. In addition to estrogen dependence, inflammation, KRAS gene mutations, immune system dysregulation, and epithelial-mesenchymal transition are thought to play significant and overlapping roles in the pathogenesis of both conditions, acting as common risk factors for their development[19]. Therefore, the coexistence of endometrial cancer and adenomyosis should not be considered a rare event. Clinically, the coexistence of endometrial cancer with uterine fibroids is also frequently observed. Some studies have reported that the incidence of adenomyosis in postoperative uterine specimens from patients with endometrial cancer is comparable to that observed in specimens from patients with other gynecological conditions[16].\u003c/p\u003e\u003cp\u003eEndometrial cancer and adenomyosis can coexist within the uterine body either independently, without pathological interaction, or with cancer spreading from the eutopic endometrium into adenomyotic foci\u0026mdash;or, more rarely, from ectopic endometrial tissue to the eutopic endometrium[23]. A pathological hallmark of endometrial cancer involving adenomyosis is that the cancerous lesion within adenomyosis is typically surrounded by normal endometrial stroma or glands. One such case was identified in the current study. Malignant transformation of ectopic glandular epithelium in adenomyosis is extremely rare, and diagnosis is particularly challenging when the lesion is contiguous with eutopic endometrium. In a retrospective study by Chao et al.[24], among 2080 patients who underwent surgery for endometrial cancer, only 28 cases were diagnosed as adenomyosis-derived malignancy, yielding an incidence of less than 1%. In these cases, p53 mutations were present in approximately 50% of patients, and the predominant histologic subtype was non-endometrioid carcinoma[25]. The rate of metastasis does not appear to differ between cancers originating in adenomyosis and those arising in the eutopic endometrium. However, disease-free survival is reportedly lower in patients with adenomyosis-derived endometrial cancer, and overall prognosis tends to be poorer[26]. Conversely, some studies have suggested that prognosis is comparable between adenomyosis-induced endometrial cancer and cancer that secondarily involves adenomyotic foci, although the former may present with more extensive myometrial invasion[27]. Immunohistochemical expression of CD10 has been reported to assist in identifying cancers that originate from adenomyotic tissue[18][28].\u003c/p\u003e\u003cp\u003eThis 2017 retrospective single-center study found no statistically significant difference in molecular subtype distribution between endometrioid carcinoma with adenomyosis and endometrioid adenocarcinoma without adenomyosis. Survival analysis confirmed no significant difference in PFS between the EC-A and EC groups. These results suggest that prognosis in the EC-A group is comparable to that of the EC group. However, the proportion of participants classified as stage IIIA was significantly higher in the EC-A group compared with the EC group (19% versus 0.9%). This observation may indicate stronger local invasive capacity in tumors associated with adenomyosis, which may lead to higher surgical pathological staging and increased likelihood of requiring postoperative adjuvant therapy. Although the cases included in this study were collected from 2017 to the present, molecular classification of endometrial cancer has only recently become widely used in clinical practice. Most cases still include patients diagnosed in the past few years. The accumulation of additional cases in the future will enable more in-depth research.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\n\u003cp\u003e\u003cstrong\u003eAssistance with the study:\u0026nbsp;\u003c/strong\u003enone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement:\u003c/strong\u003e The authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u003c/strong\u003e\u0026nbsp; The data that support the findings of this study are available from the corresponding authors upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Statement\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e Ethical approval was obtained from the Xuanwu Hospital of Capital Medical University, The data collection and analysis methods were performed in accordance with relevant guidelines and regulations in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate declaration:\u0026nbsp;\u003c/strong\u003eEvery participant gave consent to participate\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e There is no potential conflict of interest to disclose. This work was not supported by any funding agency.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAuthor ContributionsYunan Zhao (First Author): Conceptualization, Data Curation, Formal Analysis,Investigation,Methodology, Project administration,Visualization, Writing- Original Draft, WritingReview \u0026amp; Editing;Xian Zhang: Data Curation, Formal Analysis, Investigation,Methodology, Project administration,Supervision, Writing- Review \u0026amp; EditingXiaguang Shen: Data Curation, Formal Analysis, Investigation, Writing- Review \u0026amp; EditingQingquan Zhang: Data Curation, Formal Analysis, Investigation, Writing- Review \u0026amp; EditingXuan Wang: Data Curation, Formal Analysis, Supervision,Writing- Review \u0026amp; EditingPeng Dong: Data Curation, Formal Analysis, Writing- Review \u0026amp; EditingLian e Zhou: Formal Analysis, Investigation, Methodology, Writing- Review \u0026amp; EditingShijun wang (Corresponding Author): Conceptualization, Data Curation, Formal, Analysis, Funding acquisition,Investigation,Methodology, Project administration, Resources, Supervision,Writing- Original Draft, WritingReview \u0026amp; Editing;\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe manuscript has been edited to ensure language and grammar accuracy and is error free in these aspects. The edit was performed by professional editors at Editage, a brand of Cactus Communications.Thank you for the editor's work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChhikara BS, Parang K. Global Cancer Statistics 2022: the trends projection analysis[J]. Chem Biology Lett. 2023;10(1):451\u0026ndash;451.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLu KH, Broaddus RR. Endometrial cancer. N Engl J Med. 2020;383(21):2053\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eURICK M E, BELL DW. Clinical actionability of molecular targets in endometrial cancer [J]. Nat Rev Cancer. 2019;19(9):510\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCancer Genome Atlas Research Network, SCHULTZ KANDOTHC. Integrated genomic characterization of endometrial carcinoma [J]. 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Cancer Epidemiol. 2021;73:101934.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"endometrial carcinoma, adenomyosis, Molecular typing","lastPublishedDoi":"10.21203/rs.3.rs-8222275/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8222275/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground/Objectives: \u003c/strong\u003eTo study the molecular classification of endometrial cancer combined with adenomyosis and compare its differences in molecular classification and clinicopathological characteristics with endometriosis adenocarcinoma without simultaneous adenomyosis, in order to evaluate the prognosis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e A total of 131 cases of patients with endometrial cancer who underwent initial surgical treatment at Xuanwu Hospital, Capital Medical University from January 1, 2017 to December 31, 2024 were selected for retrospective analysis, Compare the differences in molecular typing and clinicopathological characteristics between 21 cases of endometrial cancer combined with adenomyosis and 110 cases of endometriosis adenocarcinoma without simultaneous adenomyosis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e There was no statistically significant difference in molecular typing between endometrial cancer combined with adenomyosis and endometriosis adenocarcinoma without simultaneous adenomyosis ( P=0.398), There were statistically significant differences in the surgical pathological stage and serum CA125 level between the two groups of patients( P\u0026lt;0.05、P=0.029;P\u0026lt;0.05、P=0.005). There were no statistically significant differences between the two groups of patients in terms of height, age, weight, BMI, menopause, vaginal bleeding, uterine cavity space-occupying lesion, vaginal discharge, number of pregnancies, number of deliveries, family history, combined hypertension or diabetes, endometrial thickness, degree of pathological differentiation, LVSI, lesion size and depth of myometrial invasion. No significant differences in general. \u003cstrong\u003eConclusion:\u003c/strong\u003e EC complicated with adenomyosis is an estrogen-dependent tumor, most of which are adenocarcinoma by histopathology. The molecular subtype of EC complicated with adenomyosis is different with endometriosis adenocarcinoma without simultaneous adenomyosis, but the CA125 level is higher and the local invasion ability of the tumor is stronger.\u003c/p\u003e","manuscriptTitle":"Molecular classification and clinical significance of endometrial cancer complicated with adenomyosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-15 01:08:39","doi":"10.21203/rs.3.rs-8222275/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-05T10:42:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-23T09:51:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-19T08:37:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-16T12:25:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"199935003291592852578739168270236233972","date":"2026-04-16T12:00:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"149490511879805992154912633465532541774","date":"2026-04-16T11:56:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6856932058792334846907313289109153936","date":"2026-04-14T14:09:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"56065353105625788848036464837068672345","date":"2026-04-14T12:21:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331794782405015133479944709899963678129","date":"2026-04-13T18:34:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-09T16:45:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-09T16:44:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-08T13:36:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-07T06:18:28+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Women's Health","date":"2025-12-07T06:12:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-womens-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bmwh","sideBox":"Learn more about [BMC Women's Health](http://bmcwomenshealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bmwh/default.aspx","title":"BMC Women's Health","twitterHandle":"","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"88c4e5b3-2965-4eab-8864-c384a7993144","owner":[],"postedDate":"December 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-15T01:08:40+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-15 01:08:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8222275","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8222275","identity":"rs-8222275","version":["v1"]},"buildId":"B-jG_2CBjPDmsCi4Wdhf-","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}