Immunohistochemical Expression of CD24 and Its Correlation with Clinicopathological Features in Malignant Surface Epithelial Tumors of the Ovary

Immunohistochemical Expression of CD24 and Its Correlation with Clinicopathological Features in Malignant Surface Epithelial Tumors of the Ovary | 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 Immunohistochemical Expression of CD24 and Its Correlation with Clinicopathological Features in Malignant Surface Epithelial Tumors of the Ovary Gena Abdel Azeem, Nadia Atwan, Mie Ali Mohamed, Ahmed Eltantawy, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6235263/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Surface epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy, mainly due to late-stage diagnosis and therapeutic resistance. Intratumoral heterogeneity, driven by cancer stem cells (CSCs), contributes to metastasis, recurrence, and therapy resistance. Cluster of Differentiation 24 (CD24) has emerged as a promising biomarker linked to tumor progression, metastasis, and immune evasion, but further research is needed to understand its role in ovarian cancer progression and patient outcomes. Aim This study investigates the immunohistochemical expression of CD24 in malignant surface epithelial ovarian tumors and its correlation with clinicopathological parameters and patient outcomes. Methods We performed a retrospective cohort analysis involving 117 formalin-fixed, paraffin-embedded (FFPE) samples of malignant ovarian surface epithelial tumors, retrieved from the archives of the Surgical Pathology Laboratory at our University oncology center in the period between 2018 and 2021. Patients underwent surgical resection, with follow-up data collected until 2024. Immunohistochemical (IHC) staining for CD24 was performed, and expression levels were assessed based on staining percentage and intensity. The correlation between CD24 expression and clinicopathological factors, disease-free survival (DFS), and overall survival (OS) was analyzed using appropriate statistical methods, including Kaplan-Meier survival analysis and Cox regression. Results CD24 expression was observed in 61.5% of cases, with varying expression levels: low (17.9%), moderate (23.1%), and high (20.5%). High CD24 expression was predominantly observed in HGSC (p = 0.02) and was significantly associated with advanced FIGO stage (p = 0.001), high tumor grade (p = 0.001), lymph node involvement (p = 0.001), positive peritoneal cytology (p = 0.001), and distant metastases (p = 0.085). Survival analysis revealed that patients with high CD24 expression exhibited significantly shorter DFS (p = 0.001) and a non-significant trend toward reduced OS (p = 0.499), compared to those with lower or absent expression. Cox regression identified CD24 as an independent predictor of poor prognosis, alongside age, tumor stage, and lymph node involvement. Conclusion CD24 overexpression in surface epithelial ovarian cancer is strongly correlated with aggressive tumor behavior, advanced stage, and poor survival outcomes. These findings support the incorporation of CD24 expression into risk stratification models and highlight the potential of CD24-targeted therapies to improve ovarian cancer outcomes. Ovarian cancer Surface epithelial tumors CD24 Intratumoral heterogeneity Cancer stem cells (CSCs) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background Ovarian cancer continues to be the deadliest type of gynecological cancer and is recognized as the fifth most common cause of cancer mortality among women globally [ 1 ]. Most patients are identified at later stages (FIGO stages III–IV) because the disease typically progresses without noticeable symptoms and lacks reliable early detection strategies [ 2 ]. Despite advances in cytoreductive surgery and platinum-based chemotherapy, high recurrence rates and chemoresistance represent significant clinical challenges, with most patients experiencing disease relapse within two years of first-line treatment [ 3 , 4 ]. Among ovarian cancer subtypes, surface epithelial tumors constitute the most prevalent group, accounting for nearly 90% of all ovarian malignancies [ 4 , 5 ]. These tumors exhibit intratumoral heterogeneity, which drives tumor progression, metastatic spread, and therapeutic resistance. High grade serous carcinoma (HGSC), in particular, represents the most aggressive and treatment-resistant epithelial ovarian tumor, often presenting with widespread peritoneal dissemination at the time of diagnosis [ 6 ]. The high mortality rate associated with ovarian cancer is primarily due to late-stage diagnosis, tumor heterogeneity, and resistance to chemotherapy. The lack of robust prognostic markers limits the ability to predict disease progression and identify high-risk patients who may benefit from targeted therapeutic strategies [ 3 ]. Recent research has identified Cluster of Differentiation 24 (CD24) as a potential tumor-specific biomarker for tumor aggressiveness and prognosis in ovarian cancer [ 7 ]. CD24 is a glycosylphosphatidylinositol (GPI)-anchored surface protein involved in multiple oncogenic processes, including; epithelial-mesenchymal transition (EMT) via the PI3K/Akt and MAPK signaling pathways [ 8 ], cancer stem cell (CSC) properties as chemo-resistance and self-renewal capacity which contribute to tumor progression and recurrence [ 9 ], and immune evasion that suppresses anti-tumor immunity [ 10 ]. High CD24 expression has been correlated with poor survival outcomes, therapy resistance, and increased metastatic potential in ovarian cancer patients [ 11 ]. However, the exact role of CD24 in ovarian cancer progression, metastasis, and patient outcomes remains incompletely understood. Investigating the correlation between CD24 expression and clinicopathological parameters in ovarian cancer may provide new insights into its potential as a diagnostic and prognostic biomarker. Furthermore, the identification of reliable prognostic biomarkers is crucial for enhancing early diagnosis, stratifying patient risk, and developing individualized treatment strategies for ovarian cancer. The primary aim of this study was to investigate the immunohistochemical expression of CD24 in malignant surface epithelial tumors of the ovary and its correlation with clinicopathological features and patient outcomes. Materials and Methods Study Design and Setting This retrospective cohort study included 117 formalin-fixed, paraffin-embedded (FFPE) tissue specimens collected from cases diagnosed with malignant surface epithelial ovarian tumors at our university’s oncology center over a four-year period from between January 2018 and December 2021. The patients underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, and the FFPE tissue blocks were retrieved from the electronic archives of the Surgical Pathology Laboratory at the same center. This research received ethical approval from the Institutional Research Board (IRB) at our faculty (Code Number: MDP.21.07.71, 2021). The study complied with the latest revision of the Helsinki Declaration on ethical guidelines for medical research involving human subjects [ 12 ]. Inclusion & Exclusion Criteria The study included cases with confirmed histopathological diagnosis of malignant surface epithelial ovarian tumors, comprehensive clinical and histopathological data, and paraffin blocks with adequate quality suitable for immunohistochemical analysis. Cases with incomplete or missing clinical data, insufficient or degraded quality, or lost follow-up were excluded from the study. Clinicopathological Data Collection The clinicopathological data for the 117 cases included age, histological type, tumor grade, tumor stage, lymph node involvement, cytology, peritoneal involvement, omental involvement, and any distant metastases present. Histological subtyping was done according to the current fifth edition (2020) of the WHO Classification of Female Genital Tumors [ 5 ]. Tumor grading was done according to the two-tier grading system (High, Low) adopted by the MD Anderson Cancer Center group [ 13 ]. Tumor staging was performed following the guidelines of the International Federation of Gynecology and Obstetrics (FIGO) classification system [ 14 ]. The follow-up information focused on the length of follow-up (in months), and whether patients experienced relapse (either locally or distant metastasis) as determined by radiological or histopathological investigations, disease-free survival (DFS) from primary surgery to documented relapse, overall survival (OS) from the date of initial surgery until death due to the disease or the last documented follow-up. Immunohistochemistry Immunostaining was carried out on 4µm-cut sections utilizing the Autostainer Link 48 (Dako) along with its recommended reagents and pharmDx kits, using the EnVision™ FLEX Visualization Systems (Link code K8000) and EnVision FLEX Hematoxylin (Link code K8008). The staining process followed the manufacturer's standardized procedure, pre-set in the autostainer's software. Immunostaining was carried out using CD24 (SN3), mouse monoclonal anti-human antibody (Quartett, Berlin, Germany, clone SN3, ready to use). The immunohistochemical staining was interpreted semi quantitatively by two independent pathologists using an ordinary light microscope. CD24-positive staining was detected when a membranous and/or cytoplasmic staining was observed. Each section was evaluated for the percentage of stained tumor cells and the staining intensity. The percentage of stained tumor cells was categorized as follows: score 0 (no staining), score 1 (1–40%), score 2 (41–80%), and score 3 (> 80%). The staining intensity was scored as 0 (negative), 1 (mild), 2 (moderate), and 3 (strong staining). The final score was obtained by multiplication of staining percentage score by the staining intensity score. The final score was coded as Negative (0), Low (1–2), Moderate (3–4), or High (6–9) [ 15 ]. Statistical Analysis Statistical analysis was conducted using SPSS software version 26 (SPSS Inc., PASW Statistics for Windows, version 26, Chicago: SPSS Inc.). Qualitative variables were presented as frequencies and percentages. Quantitative variables were summarized as mean ± standard deviation for data that followed a normal distribution, which was verified by applying the Kolmogorov-Smirnov test. Appropriate statistical tests, such as Chi-square, Fisher's exact, and Monte Carlo tests, were utilized to assess qualitative differences between groups. Kaplan-Meier analysis was applied to determine differences in disease-free survival (DFS) and overall survival (OS) among groups categorized by CD24 expression levels. Additionally, Cox regression analysis was conducted to control for possible confounding factors and to identify prognostic factors independently influencing patient outcomes. A p-value ≤ 0.05 was considered statistically significant, and results were classified as non-significant (p > 0.05), significant (p ≤ 0.05), or highly significant (p ≤ 0.001). Results Table (1) provides an overview of the demographic and pathological characteristics of the studied cases. The average age of patients is 57.56 years, with 53% being under 60 years old. The majority of cases are high-grade serous carcinoma (77.8%,), and advanced stages (III and IV) account for more than half of the studied cases (53%). Lymph node involvement (29.9%) and positive cytology (59.8%) indicate a significant burden of disease. Additionally, the presence of peritoneal and omental involvement in 53.8% of cases highlights the aggressive nature of the tumors. Distant metastasis was identified in 41% of the cases, indicating a substantial proportion of patients presenting with widespread disease. Table ( 1 ): Clinicopathological Characteristics of The Studied Cases N=117 % Age / years Mean ±SD Median (range) 57.56±8.55 58(35-83) <60 ≥60 62 55 53.0 47.0 Type HGSC LGSC Mucinous Endometroid Clear Cell 91 9 7 8 2 77.8 7.7 6.0 6.8 1.7 Grade Low High 17 100 14.5 85.5 Stage I II III IV 41 14 54 8 35.0 12.0 46.2 6.8 LN involvement Negative Positive 82 35 70.1 29.9 Cytology Negative Positive 47 70 40.2 59.8 Peritoneal involvement Negative Positive 54 63 46.2 53.8 Omentum involvement Negative Positive 54 63 46.2 53.8 Distant metastasis Negative Positive 69 48 59.0 41.0 Relapse No Yes 93 24 79.5 20.5 Type of relapse Local Relapse Distant Mets N=24 2 22 8.3 91.7 Death 6 5.1 The results of IHC expression of CD24 staining are shown in table (2). CD24 expression analysis revealed a heterogeneous pattern: 38.5% of cases showed no staining (Figure 1), while 35.9% exhibited low percentage of expression (1–40%). Moderate (40–80%) and high (>80%) percentages of expression were observed in 13.7% and 12% of cases, respectively. Intensity analysis indicated that strong staining was most common (34.2%), followed by moderate (17.1%) and weak (10.3%) staining intensity. This variation in expression intensity may reflect differences in tumor biology and potential outcomes. The final CD24 expression combined score was low in 17.9% of cases (Figure 2), moderate in 23.1% (Figure 3), and high in 20.5% of cases (Figure 4). Table (2): Immunohistochemical Staining Results of CD24 Among Studied Cases N=117 % CD24 Expression Positivity Negative Positive 45 72 38.5 61.5 CD24 Staining Percentage none 1–40% 40–80% >80% 45 42 16 14 38.5 35.9 13.7 12.0 CD24 Staining Intensity no staining weak moderate Strong 45 12 20 40 38.5 10.3 17.1 34.2 CD24 Expression Levels Negative Low Moderate High 45 21 27 24 38.5 17.9 23.1 20.5 Table (3) demonstrates the relationship between CD24 expression categories (Negative, Low, Moderate, High) and various clinic-pathological characteristics, highlighting significant associations with tumor aggressiveness, metastasis, and patient outcomes. High CD24 expression was strongly linked to older age, with 79.2% of patients aged ≥60 showing high expression (p=0.001). Additionally, high CD24 expression was most prevalent in high-grade serous carcinoma (HGSC), with 95.8% of HGSC cases exhibiting high expression (p=0.02), and no cases of high expression were found in mucinous or clear cell carcinomas. All tumors with high CD24 expression were high-grade, with the majority being stage III (70.8%) or stage IV (16.7%) (p=0.001). Furthermore, high CD24 expression was significantly associated with lymph node involvement (54.2%), positive cytology, and peritoneal spread (91.7%), with both lymph node involvement and peritoneal spread showing a p-value of 0.001. These findings suggest that high CD24 expression is closely linked to advanced disease features and poor prognosis. There was also a clear association between CD24 expression levels and adverse clinical outcomes. As CD24 expression increased, the relapse rate progressively increased, reaching 75% in the high-expression group (p=0.001), indicating a strong link between elevated CD24 levels and higher relapse risk. Additionally, patients with high CD24 expression experienced a significantly higher mortality rate, with 25% of them dying during the study period. These findings suggest that CD24 expression may serve as a prognostic biomarker for recurrence risk and as a potential predictor of poor survival outcomes. Table (3): Relation Between CD24 Expression Levels and Clinicopathological Features of Studied Cases CD 24 Expression Test of Significance Negative N=45 Low N=21 Moderate N=27 High N=24 Age / years <60 ≥60 36(80) 9(20) 9(42.9) 12(57.1) 12(44.4) 15(55.6) 5(20.8) 19(79.2) ꭓ 2 =24.79 P=0.001* Type HGSC LGSC Mucinous Endometroid Clear Cell 26(57.8) 6(13.3) 7(15.6) 4(8.9) 2(4.4) 17(81) 2(9.5) 0 2(9.5) 0 25(92.6) 1(3.7) 0 1(3.7) 0 23(95.8) 0 0 1(4.2) 0 ꭓ 2MC =24.02 P=0.02* Grade Low High 14(31.1) 31(68.9) 2(9.5) 19(90.5) 1(3.7) 26(96.3) 0 24(100) ꭓ 2MC =17.01 P=0.001* Stage I II III IV 27(60) 5(11.1) 12(26.7) 1(2.2) 6(28.6) 3(14.3) 12(57.1) 0 7(25.9) 4(14.8) 13(48.1) 3(11.1) 1(4.2) 2(8.3) 17(70.8) 4(16.7) ꭓ 2 =30.38 P=0.001* LN involvement Negative Positive 40(88.9) 5(11.1) 15(71.4) 6(28.6) 16(59.3) 11(40.7) 11(45.8) 13(54.2) ꭓ 2 =15.85 P=0.001* Cytology Negative Positive 28(62.2) 17(37.8) 8(38.1) 13(61.9) 10(37.0) 17(63.0) 1(4.2) 23(95.8) ꭓ 2 =22.19 P=0.001* Peritoneal involvement Negative Positive 31(68.9) 14(31.1) 9(42.9) 12(57.1) 12(44.4) 15(55.6) 2(8.3) 22(91.7) ꭓ 2 =23.29 P=0.001* Omental involvement Negative Positive 31(68.9) 14(31.1) 9(42.9) 12(57.1) 12(44.4) 15(55.6) 2(8.3) 22(91.7) ꭓ 2 =23.29 P=0.001* Distant metastasis Negative Positive 31(68.9) 14(31.1) 11(52.4) 10(47.6) 19(70.4) 8(29.6) 8(33.3) 16(66.7) ꭓ 2 =10.18 P=0.017* Relapse No Yes 44(97.8) 1(2.2) 18(85.7) 3(14.3) 25(92.6) 2(7.4) 6(25) 18(75) ꭓ 2MC =56.28 P=0.001* Type of relapse Local Relapse Distant Mets 0 1(100) 0 3(100) 0 2(100) 2(11.1) 16(88.9) ꭓ 2MC =0.727 P=0.867 Death 0 0 0 6(25) ꭓ 2MC =24.51 P=0.001* ꭓ 2 =Chi-Square test, MC: Monte Carlo test, *statistically significant Data are expressed as number (%) The cohort had a median disease-free survival (DFS) duration of 74.68 months (95% CI:69.85–79.52). The DFS rate was 90.6% at 1 year, 87.2% at 2 years, and 80.3% at 3 years. The survival curve shows a gradual decline over time, with most patients remaining disease-free during the follow-up period. Censoring is frequent in later months, indicating a high proportion of patients remained disease-free. Disease-free survival (DFS) was closely linked to CD24 expression levels, with high CD24 expression associated with a marked reduction in DFS ( 31.50 months) , characterized by a sharp early decline in survival probability. In contrast, patients with negative CD24 expression displayed the most favorable DFS ( 86.31 months) , maintaining stable survival over the follow-up period (Figure 5). These results highlight high CD24 expression as an independent predictor of poor DFS and early recurrence, suggesting its potential as a crucial biomarker for prognosis. The Cox regression analysis identifying several key predictors of disease-free survival (DFS) including age, stage, lymph node involvement, positive cytology, peritoneal-omental involvement, distant metastasis at time of diagnosis and CD 24 expression. High CD24 expression is particularly striking, with an HR of 48.06 (95% CI 6.38-300.56, p=0.001), indicating a very high risk of disease recurrence in patients with elevated CD24 levels. This reinforces high CD24 expression as a crucial independent prognostic marker for disease-free survival. Low and moderate CD24 expression did not reach statistical significance, suggesting a potential dose-response relationship where only high expression is clinically relevant for predicting poor outcomes ( Table 4). Table (4): Cox Regression for Predictors of Disease-Free Survival (DFS) by CD24 Expression Levels among studied cases β p value Hazard Ratio (95%CI) CD24 Expression Positivity Negative (R) Positive R 2.77 0.007* R 15.89(2.15-100.58) CD24 Staining Percentage none 1–40% 40–80% >80% R 1.15 3.62 3.83 0.318 0.001* 0.0001* R 3.17(0.330-30.47) 37.17(4.69-294.67) 46.13(5.94-350.4) CD24 Staining Intensity no staining weak moderate Strong R 2.01 2.87 2.88 0.101 0.007* 0.005* R 7.45(0.676-82.17) 17.59(2.17-143.09) 17.96(2.36-136.69) CD24 Expression Levels Negative Low Moderate High R 1.847 1.240 3.872 0.110 0.311 0.001* R 6.34(0.660-60.95) 3.46(0.313-38.11) 48.06(6.38-300.56) R: reference group The median overall survival (OS) for the studied cohort was 85.04 months (95% CI: 82.72–96.80). The 2-year survival rate was 97.4%, while the 3-year survival rate was 95.7%. The survival curve shows a high overall survival rate for the studied population, with a gradual decline over time. The majority of events appear censored, indicating that a large proportion of patients were still alive at the end of the study period. This reflects relatively favorable outcomes in the early years of follow-up. CD24-positive cases had significantly lower OS than CD24-negative cases (p=0.049), and high CD24 expression was significantly associated with OS (p=0.001). High CD24 expression was linked to the shortest survival compared to other expression levels. The survival analysis for patients with high-grade CD24 expression revealed a progressive decline in survival over time. The 2-year survival rate was 87.5%, which dropped to 79.2% at 3 years and further decreased to 73.9% at 4 years (Figure 6). Cox regression analysis identified Lymph Node Involvement as an independent predictor of overall survival (HR=12.46, p=0.021). High CD24 expression was associated with a higher risk of death, although the specific hazard ratio could not be fully estimated (undefined), reflecting the significant but complex relationship between CD24 expression and survival outcomes. OS analysis showed a non-significant trend toward worse survival in high CD24 expression cases (p=0.499), suggesting a need for further validation in larger cohorts. These results emphasize the importance of lymph node involvement and CD24 expression as critical factors in predicting overall survival in ovarian carcinoma. The undefined values for some variables indicate the need for further investigation with larger cohorts to refine the predictive power of the model. Clinically, this emphasizes the multifactorial nature of survival in ovarian cancer and the need to consider multiple prognostic factors when planning treatment. Discussion This study investigated the immune-histochemical expression of CD24 in malignant surface epithelial ovarian tumors and its correlation with clinic-pathological parameters and patient outcomes. The findings indicated a significant link between elevated CD24 expression and advanced tumor stage, high-grade tumors, increased lymph node involvement, peritoneal and omental metastasis, and poor survival outcomes. Patients showing elevated CD24 levels had notably reduced disease-free survival (DFS) and overall survival (OS) compared to patients with low or negative expression. These findings align with the broader understanding that CD24 functions as an oncogenic driver in various malignancies, playing a crucial role in tumor aggressiveness by promoting epithelial-mesenchymal transition (EMT), immune evasion, and metastatic potential [ 11 , 16 ]. The statistical significance observed in this study strengthens the hypothesis that CD24 is not merely an incidental marker but a potential contributor to the aggressive behavior of ovarian tumors. Specifically, our Kaplan-Meier survival analysis and Cox regression models in this study confirmed that CD24 overexpression is an independent predictor of poor prognosis, supporting its role as a valuable prognostic biomarker in ovarian cancer. These results suggest that CD24 expression could be used for patient stratification into different risk categories, potentially guiding treatment decisions. Furthermore, the strong correlation between CD24 expression and increased metastatic spread suggests that CD24 is not merely a passive marker but actively contributes to tumor dissemination. Given that CD24 enhances tumor cell adhesion, migration, and immune evasion, its high expression in advanced-stage tumors may drive disease progression and chemoresistance as stated by Jang et al., 2024 [ 17 ] and Wang et al., 2023 [ 18 ]. The results of this study align with prior research identifying CD24 as a marker of poor prognosis in ovarian cancer and other malignancies [ 11 ] [ 17 ]. Previous studies have demonstrated that CD24 expression is linked to EMT, tumor invasion, and chemoresistance, which are consistent with our results [ 16 ]. A study by Nakamura et al., 2017 [ 7 ] found that CD24 expression was significantly associated with high-grade serous ovarian carcinoma (HGSC), advanced-stage disease, and reduced survival outcomes, paralleling our findings. However, our study extends these observations by providing detailed statistical evidence linking CD24 positivity to DFS and OS, further validating its prognostic significance. Additionally, CD24 has been widely studied in breast and pancreatic cancers, where it has been implicated in metastatic dissemination and resistance to apoptosis [ 19 ]. In ovarian cancer, CD24 expression correlates with chemotherapy resistance, which underscores its potential as a therapeutic target [ 20 ]. This study reinforces these findings by showing that patients with CD24-positive tumors exhibited significantly reduced DFS and OS, highlighting its impact on ovarian cancer progression. Furthermore, the overrepresentation of CD24-positive tumors in high-grade and late-stage disease strengthens the argument that CD24 contributes to tumor progression rather than being an incidental byproduct of malignancy. These findings reinforce CD24’s potential as a prognostic biomarker. Given its strong association with adverse survival outcomes, CD24 assessment could be integrated into routine histopathological evaluations to improve patient risk stratification. Moreover, CD24-targeted therapies, such as monoclonal antibodies and immune checkpoint inhibitors, are currently under investigation and could offer new therapeutic strategies for ovarian cancer [ 18 ]. This study’s strengths lie in its robust methodology and clinical relevance, utilizing a well-defined cohort of 117 ovarian cancer cases, ensuring a statistically meaningful analysis. The standardized immunohistochemical protocols and validated scoring criteria minimized interobserver variability, while Kaplan-Meier survival curves and Cox regression models provided a comprehensive evaluation of CD24’s prognostic significance. By correlating CD24 expression with survival outcomes, the study bridges basic science and translational research, reinforcing its potential as a biomarker for risk stratification and personalized treatment. However, limitations include its retrospective design and single-center setting, which may limit generalizability. Additionally, the lack of functional assays prevents a mechanistic understanding of CD24 role in ovarian cancer progression, and variability in treatment regimens introduces potential confounders. Confounding factors such as genetic variations and treatment responses were not fully accounted for in the statistical models, which could influence the observed associations. Future studies should incorporate comprehensive genomic profiling and prospective validation cohorts to strengthen the clinical relevance of these findings. Conclusion In summary, this study highlights the significant association between CD24 expression and poor clinical outcomes in ovarian cancer. High CD24 expression correlates with advanced tumor stage, high-grade tumors, increased metastasis, and reduced survival rates, reinforcing its role as a prognostic biomarker. Routine assessment of CD24 expression in ovarian cancer histopathology may enhance patient risk stratification, guiding both prognosis and therapeutic decisions. Future studies should aim to confirm these results in larger patient groups and investigate potential therapeutic approaches directed at CD24 to improve ovarian cancer management and patient survival outcomes. Abbreviations 1. CD24 - Cluster of Differentiation 24 2. CSC - Cancer Stem Cells 3. EMT - Epithelial-Mesenchymal Transition 4. FFPE - Formalin-Fixed, Paraffin-Embedded 5. IHC - Immunohistochemistry 6. HGSC - High-Grade Serous Carcinoma 7. LGSC - Low-Grade Serous Carcinoma 8. FIGO - International Federation of Gynecology and Obstetrics 9. DFS - Disease-Free Survival 10. OS - Overall Survival 11. 3YS - 3-Year Survival 12. HR - Hazard Ratio 13. CI - Confidence Interval 14. LN - Lymph Node 15. MC - Monte Carlo 16. R - Reference group Declarations Ethics Approval and Consent to participate This research received ethical approval from the Institutional Research Board (IRB) of the University Faculty of Medicine (Code Number: MDP.21.07.71, 2021). Confidentiality was maintained by using pathology identification numbers instead of patient names. The study complied with the latest revision of the Helsinki Declaration on ethical guidelines for medical research involving human subjects (The World Medical Association, 2013). After completion, all paraffin tissue blocks were returned to the archives to allow potential future use for clinical or research purposes. Consent For Publication The authors unanimously agree to publish the data and information in the manuscript. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Author Contribution • G. A. A.: Conceptualization, Methodology, Data analysis, Manuscript drafting.• N. A.: Supervision, Critical review, Methodology guidance.• M. A. M.: Literature review, Methodological oversight, Manuscript revision.• A. E.: Literature review, Statistical Analysis.• M. M. A. F. Z.: Literature review, Data validation, Manuscript editing.AcknowledgmentsThe authors acknowledge the Pathology Department, Faculty of Medicine, Mansoura University, for providing resources and facilities for this study.FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Acknowledgement The authors acknowledge the Pathology Department, Faculty of Medicine, Mansoura University, for providing resources and facilities for this study. Data Availability The datasets used and analyzed during this study are available from the corresponding author upon reasonable request. References Lheureux S, Gourley C, Vergote I , et al. Epithelial ovarian cancer. Lancet (London, England). 2019;393(10177):1240-53. 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CD24 induced cellular quiescence-like state and chemoresistance in ovarian cancer cells via miR-130a/301a-dependent CDK19 downregulation. Cell Death Discovery. 2024;10(1):81. Gu Y, Zhou G, Tang X , et al. The biological roles of CD24 in ovarian cancer: old story, but new tales. Frontiers in immunology. 2023;14. Kim S, Park JM, Park S , et al. Suppression of TNBC metastasis by doxazosin, a novel dual inhibitor of c-MET/EGFR. Journal of Experimental & Clinical Cancer Research. 2023;42(1):292. Fang X, Zheng P, Tang J , et al. CD24: from A to Z. Cellular & molecular immunology. 2010;7(2):100-3. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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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-6235263","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":431428248,"identity":"5d163320-6697-4832-be7f-b7289aad6d35","order_by":0,"name":"Gena Abdel Azeem","email":"data:image/png;base64,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","orcid":"","institution":"Mansoura University","correspondingAuthor":true,"prefix":"","firstName":"Gena","middleName":"Abdel","lastName":"Azeem","suffix":""},{"id":431428249,"identity":"aa5cdc40-9d75-4173-9ba9-049bb5ebac4b","order_by":1,"name":"Nadia Atwan","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Nadia","middleName":"","lastName":"Atwan","suffix":""},{"id":431428250,"identity":"b2964e8e-4481-47e2-9cb4-738784cdb544","order_by":2,"name":"Mie Ali Mohamed","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Mie","middleName":"Ali","lastName":"Mohamed","suffix":""},{"id":431428251,"identity":"99646b82-e12f-4f19-8047-04b1944baf7d","order_by":3,"name":"Ahmed Eltantawy","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"","lastName":"Eltantawy","suffix":""},{"id":431428252,"identity":"b54b317d-4002-449f-8cfb-feff09d7f0e6","order_by":4,"name":"Marwa Mohamed Abdel Fattah Zaki","email":"","orcid":"","institution":"Mansoura University","correspondingAuthor":false,"prefix":"","firstName":"Marwa","middleName":"Mohamed Abdel Fattah","lastName":"Zaki","suffix":""}],"badges":[],"createdAt":"2025-03-16 02:08:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6235263/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6235263/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79574964,"identity":"862049b5-77d6-4982-a6aa-7a5d74ff4a54","added_by":"auto","created_at":"2025-03-31 11:12:47","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":116319,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e Case of clear cell carcinoma of the ovary (H\u0026amp;E; x100). \u003cstrong\u003e(B)\u003c/strong\u003e CD24 negative tumor cells in the same case with no membranous or cytoplasmic staining in any of the tumor cells (Negative CD24 expression, Score = Zero; x200).\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6235263/v1/2e1f6ec8fc8c5c90e3cb7017.jpg"},{"id":79574967,"identity":"7670060a-a161-49c0-bb36-e122eb7f88fa","added_by":"auto","created_at":"2025-03-31 11:12:47","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":118508,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e Case of high-grade endometrioid carcinoma of the ovary (H\u0026amp;E; x100). \u003cstrong\u003e(B)\u003c/strong\u003e CD24 positive tumor cells in the same case with moderate membranous and cytoplasmic staining in (1-40%) of the tumor cells (Low level of CD24 expression, Score 2×1=2; x400).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6235263/v1/bcc243b8c32838900b0bcc32.jpg"},{"id":79574966,"identity":"be539931-cd23-4a83-b61c-b068df58c776","added_by":"auto","created_at":"2025-03-31 11:12:47","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":115440,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e Case of high-grade serous carcinoma of the ovary (H\u0026amp;E; x200). \u003cstrong\u003e(B)\u003c/strong\u003e CD24 positive tumor cells in the same case with moderate membranous and cytoplasmic staining intensity in (40-80%) of tumor cells (Moderate level of CD24 expression, Score 2×2=4; x200).\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6235263/v1/17cfea9ef33253462562e626.jpg"},{"id":79574968,"identity":"58f3ebf6-4e80-4dc8-a0d2-10e879dc8af7","added_by":"auto","created_at":"2025-03-31 11:12:47","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":135173,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A)\u003c/strong\u003e Case of high-grade serous carcinoma of the ovary (H\u0026amp;E; x200). \u003cstrong\u003e(B)\u003c/strong\u003e CD24 positive tumor cells in the same case with strong membranous and cytoplasmic staining intensity in more than 80% of tumor cells (High level of CD24 expression, Score 3×3=9; x400).\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6235263/v1/9d9b7a5112cf3134ca18a1d9.jpg"},{"id":79574973,"identity":"8bc2e39b-7ff9-4518-be59-7ecf528e8bbf","added_by":"auto","created_at":"2025-03-31 11:12:47","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":52206,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier Curve of Disease-Free Survival by CD24 Expression Levels\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6235263/v1/90fa194b2ce542b5acbc724a.jpg"},{"id":79574971,"identity":"b99c3d48-08e2-4fb7-81eb-004cf8284ebc","added_by":"auto","created_at":"2025-03-31 11:12:47","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":39337,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier Curve of Overall Survival by CD24 Expression Levels\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6235263/v1/a53d858e2289af41127ab6e5.jpg"},{"id":99029530,"identity":"1dbabf2a-6ef4-4802-866b-b5f0e22bef76","added_by":"auto","created_at":"2025-12-26 08:10:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1943875,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6235263/v1/f86ab9d5-196c-4957-98fc-a95d445a67b0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Immunohistochemical Expression of CD24 and Its Correlation with Clinicopathological Features in Malignant Surface Epithelial Tumors of the Ovary","fulltext":[{"header":"Background","content":"\u003cp\u003eOvarian cancer continues to be the deadliest type of gynecological cancer and is recognized as the fifth most common cause of cancer mortality among women globally [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Most patients are identified at later stages (FIGO stages III\u0026ndash;IV) because the disease typically progresses without noticeable symptoms and lacks reliable early detection strategies [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Despite advances in cytoreductive surgery and platinum-based chemotherapy, high recurrence rates and chemoresistance represent significant clinical challenges, with most patients experiencing disease relapse within two years of first-line treatment [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAmong ovarian cancer subtypes, surface epithelial tumors constitute the most prevalent group, accounting for nearly 90% of all ovarian malignancies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. These tumors exhibit intratumoral heterogeneity, which drives tumor progression, metastatic spread, and therapeutic resistance. High grade serous carcinoma (HGSC), in particular, represents the most aggressive and treatment-resistant epithelial ovarian tumor, often presenting with widespread peritoneal dissemination at the time of diagnosis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe high mortality rate associated with ovarian cancer is primarily due to late-stage diagnosis, tumor heterogeneity, and resistance to chemotherapy. The lack of robust prognostic markers limits the ability to predict disease progression and identify high-risk patients who may benefit from targeted therapeutic strategies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eRecent research has identified Cluster of Differentiation 24 (CD24) as a potential tumor-specific biomarker for tumor aggressiveness and prognosis in ovarian cancer [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. CD24 is a glycosylphosphatidylinositol (GPI)-anchored surface protein involved in multiple oncogenic processes, including; epithelial-mesenchymal transition (EMT) via the PI3K/Akt and MAPK signaling pathways [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], cancer stem cell (CSC) properties as chemo-resistance and self-renewal capacity which contribute to tumor progression and recurrence [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and immune evasion that suppresses anti-tumor immunity [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHigh CD24 expression has been correlated with poor survival outcomes, therapy resistance, and increased metastatic potential in ovarian cancer patients [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, the exact role of CD24 in ovarian cancer progression, metastasis, and patient outcomes remains incompletely understood. Investigating the correlation between CD24 expression and clinicopathological parameters in ovarian cancer may provide new insights into its potential as a diagnostic and prognostic biomarker. Furthermore, the identification of reliable prognostic biomarkers is crucial for enhancing early diagnosis, stratifying patient risk, and developing individualized treatment strategies for ovarian cancer.\u003c/p\u003e \u003cp\u003eThe primary aim of this study was to investigate the immunohistochemical expression of CD24 in malignant surface epithelial tumors of the ovary and its correlation with clinicopathological features and patient outcomes.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study included 117 formalin-fixed, paraffin-embedded (FFPE) tissue specimens collected from cases diagnosed with malignant surface epithelial ovarian tumors at our university\u0026rsquo;s oncology center over a four-year period from between January 2018 and December 2021. The patients underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, and the FFPE tissue blocks were retrieved from the electronic archives of the Surgical Pathology Laboratory at the same center.\u003c/p\u003e \u003cp\u003eThis research received ethical approval from the Institutional Research Board (IRB) at our faculty (Code Number: MDP.21.07.71, 2021). The study complied with the latest revision of the Helsinki Declaration on ethical guidelines for medical research involving human subjects [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion \u0026 Exclusion Criteria\u003c/h3\u003e\n\u003cp\u003eThe study included cases with confirmed histopathological diagnosis of malignant surface epithelial ovarian tumors, comprehensive clinical and histopathological data, and paraffin blocks with adequate quality suitable for immunohistochemical analysis. Cases with incomplete or missing clinical data, insufficient or degraded quality, or lost follow-up were excluded from the study.\u003c/p\u003e\n\u003ch3\u003eClinicopathological Data Collection\u003c/h3\u003e\n\u003cp\u003eThe clinicopathological data for the 117 cases included age, histological type, tumor grade, tumor stage, lymph node involvement, cytology, peritoneal involvement, omental involvement, and any distant metastases present.\u003c/p\u003e \u003cp\u003eHistological subtyping was done according to the current fifth edition (2020) of the WHO Classification of Female Genital Tumors [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Tumor grading was done according to the two-tier grading system (High, Low) adopted by the MD Anderson Cancer Center group [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Tumor staging was performed following the guidelines of the International Federation of Gynecology and Obstetrics (FIGO) classification system [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe follow-up information focused on the length of follow-up (in months), and whether patients experienced relapse (either locally or distant metastasis) as determined by radiological or histopathological investigations, disease-free survival (DFS) from primary surgery to documented relapse, overall survival (OS) from the date of initial surgery until death due to the disease or the last documented follow-up.\u003c/p\u003e\n\u003ch3\u003eImmunohistochemistry\u003c/h3\u003e\n\u003cp\u003eImmunostaining was carried out on 4\u0026micro;m-cut sections utilizing the Autostainer Link 48 (Dako) along with its recommended reagents and pharmDx kits, using the EnVision\u0026trade; FLEX Visualization Systems (Link code K8000) and EnVision FLEX Hematoxylin (Link code K8008). The staining process followed the manufacturer's standardized procedure, pre-set in the autostainer's software. Immunostaining was carried out using CD24 (SN3), mouse monoclonal anti-human antibody (Quartett, Berlin, Germany, clone SN3, ready to use).\u003c/p\u003e \u003cp\u003eThe immunohistochemical staining was interpreted semi quantitatively by two independent pathologists using an ordinary light microscope. CD24-positive staining was detected when a membranous and/or cytoplasmic staining was observed. Each section was evaluated for the percentage of stained tumor cells and the staining intensity. The percentage of stained tumor cells was categorized as follows: score 0 (no staining), score 1 (1\u0026ndash;40%), score 2 (41\u0026ndash;80%), and score 3 (\u0026gt;\u0026thinsp;80%). The staining intensity was scored as 0 (negative), 1 (mild), 2 (moderate), and 3 (strong staining).\u003c/p\u003e \u003cp\u003eThe final score was obtained by multiplication of staining percentage score by the staining intensity score. The final score was coded as Negative (0), Low (1\u0026ndash;2), Moderate (3\u0026ndash;4), or High (6\u0026ndash;9) [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was conducted using SPSS software version 26 (SPSS Inc., PASW Statistics for Windows, version 26, Chicago: SPSS Inc.). Qualitative variables were presented as frequencies and percentages. Quantitative variables were summarized as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation for data that followed a normal distribution, which was verified by applying the Kolmogorov-Smirnov test. Appropriate statistical tests, such as Chi-square, Fisher's exact, and Monte Carlo tests, were utilized to assess qualitative differences between groups. Kaplan-Meier analysis was applied to determine differences in disease-free survival (DFS) and overall survival (OS) among groups categorized by CD24 expression levels. Additionally, Cox regression analysis was conducted to control for possible confounding factors and to identify prognostic factors independently influencing patient outcomes. A p-value\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered statistically significant, and results were classified as non-significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), significant (p\u0026thinsp;\u0026le;\u0026thinsp;0.05), or highly significant (p\u0026thinsp;\u0026le;\u0026thinsp;0.001).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTable (1) provides an overview of the demographic and pathological characteristics of the studied cases. The average age of patients is 57.56 years, with 53% being under 60 years old. The majority of cases are high-grade serous carcinoma (77.8%,), and advanced stages (III and IV) account for more than half of the studied cases (53%). Lymph node involvement (29.9%) and positive cytology (59.8%) indicate a significant burden of disease. Additionally, the presence of peritoneal and omental involvement in 53.8% of cases highlights the aggressive nature of the tumors. Distant metastasis was identified in 41% of the cases, indicating a substantial proportion of patients presenting with widespread disease.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e): Clinicopathological Characteristics of The Studied Cases\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN=117\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge / years\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn;SD\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (range)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 309px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e57.56\u0026plusmn;8.55\u003c/p\u003e\n \u003cp\u003e58(35-83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026lt;60\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026ge;60\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003cp\u003e55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e53.0\u003c/p\u003e\n \u003cp\u003e47.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHGSC\u003c/p\u003e\n \u003cp\u003eLGSC\u003c/p\u003e\n \u003cp\u003eMucinous\u003c/p\u003e\n \u003cp\u003eEndometroid\u003c/p\u003e\n \u003cp\u003eClear Cell\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e77.8\u003c/p\u003e\n \u003cp\u003e7.7\u003c/p\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003cp\u003e6.8\u003c/p\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14.5\u003c/p\u003e\n \u003cp\u003e85.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35.0\u003c/p\u003e\n \u003cp\u003e12.0\u003c/p\u003e\n \u003cp\u003e46.2\u003c/p\u003e\n \u003cp\u003e6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLN involvement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003cp\u003e35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e70.1\u003c/p\u003e\n \u003cp\u003e29.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCytology\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40.2\u003c/p\u003e\n \u003cp\u003e59.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeritoneal involvement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e46.2\u003c/p\u003e\n \u003cp\u003e53.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOmentum involvement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003cp\u003e63\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e46.2\u003c/p\u003e\n \u003cp\u003e53.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDistant metastasis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e59.0\u003c/p\u003e\n \u003cp\u003e41.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelapse\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e93\u003c/p\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e79.5\u003c/p\u003e\n \u003cp\u003e20.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of relapse\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eLocal Relapse\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDistant Mets\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003eN=24\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8.3\u003c/p\u003e\n \u003cp\u003e91.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 253px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDeath\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e5.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan id=\"_Toc191080215\"\u003eThe results of IHC expression of CD24 staining are shown in table (2). CD24 expression analysis revealed a heterogeneous pattern: 38.5% of cases showed no staining (Figure 1), while 35.9% exhibited low percentage of expression (1\u0026ndash;40%). Moderate (40\u0026ndash;80%) and high (\u0026gt;80%) percentages of expression were observed in 13.7% and 12% of cases, respectively. Intensity analysis indicated that strong staining was most common (34.2%), followed by moderate (17.1%) and weak (10.3%) staining intensity. This variation in expression intensity may reflect differences in tumor biology and potential outcomes. The final CD24 expression combined score was low in 17.9% of cases (Figure 2), moderate in 23.1% (Figure 3), and high in 20.5% of cases (Figure 4).\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(2):\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eImmunohistochemical\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eStaining Results of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCD24\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAmong Studied Cases\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 274px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN=117\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 274px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD24 Expression Positivity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003cp\u003e72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38.5\u003c/p\u003e\n \u003cp\u003e61.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 274px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD24 Staining Percentage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003enone\u003c/p\u003e\n \u003cp\u003e1\u0026ndash;40%\u003c/p\u003e\n \u003cp\u003e40\u0026ndash;80%\u003c/p\u003e\n \u003cp\u003e\u0026gt;80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38.5\u003c/p\u003e\n \u003cp\u003e35.9\u003c/p\u003e\n \u003cp\u003e13.7\u003c/p\u003e\n \u003cp\u003e12.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 274px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD24 Staining Intensity\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eno staining\u003c/p\u003e\n \u003cp\u003eweak\u003c/p\u003e\n \u003cp\u003emoderate\u003c/p\u003e\n \u003cp\u003eStrong\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38.5\u003c/p\u003e\n \u003cp\u003e10.3\u003c/p\u003e\n \u003cp\u003e17.1\u003c/p\u003e\n \u003cp\u003e34.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 274px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD24 Expression Levels\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e45\u003c/p\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 146px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38.5\u003c/p\u003e\n \u003cp\u003e17.9\u003c/p\u003e\n \u003cp\u003e23.1\u003c/p\u003e\n \u003cp\u003e20.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable (3) demonstrates the relationship between CD24 expression categories (Negative, Low, Moderate, High) and various clinic-pathological characteristics, highlighting significant associations with tumor aggressiveness, metastasis, and patient outcomes. High CD24 expression was strongly linked to older age, with 79.2% of patients aged \u0026ge;60 showing high expression (p=0.001). Additionally, high CD24 expression was most prevalent in high-grade serous carcinoma (HGSC), with 95.8% of HGSC cases exhibiting high expression (p=0.02), and no cases of high expression were found in mucinous or clear cell carcinomas.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll tumors with high CD24 expression were high-grade, with the majority being stage III (70.8%) or stage IV (16.7%) (p=0.001). Furthermore, high CD24 expression was significantly associated with lymph node involvement (54.2%), positive cytology, and peritoneal spread (91.7%), with both lymph node involvement and peritoneal spread showing a p-value of 0.001.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cspan id=\"_Toc191080217\"\u003eThese findings suggest that high CD24 expression is closely linked to advanced disease features and poor prognosis. There was also a clear association between CD24 expression levels and adverse clinical outcomes. As CD24 expression increased, the relapse rate progressively increased, reaching 75% in the high-expression group (p=0.001), indicating a strong link between elevated CD24 levels and higher relapse risk. Additionally, patients with high CD24 expression experienced a significantly higher mortality rate, with 25% of them dying during the study period. These findings suggest that CD24 expression may serve as a prognostic biomarker for recurrence risk and as a potential predictor of poor survival outcomes.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (3): Relation Between CD24 Expression Levels and Clinicopathological Features of Studied Cases\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 313px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD 24 Expression\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTest of Significance\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003eN=45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003cp\u003eN=21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003eN=27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003cp\u003eN=24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge / years\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u0026lt;60\u003c/p\u003e\n \u003cp\u003e\u0026ge;60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36(80)\u003c/p\u003e\n \u003cp\u003e9(20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9(42.9)\u003c/p\u003e\n \u003cp\u003e12(57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12(44.4)\u003c/p\u003e\n \u003cp\u003e15(55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5(20.8)\u003c/p\u003e\n \u003cp\u003e19(79.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2\u003c/sup\u003e=24.79\u003c/p\u003e\n \u003cp\u003eP=0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eHGSC\u003c/p\u003e\n \u003cp\u003eLGSC\u003c/p\u003e\n \u003cp\u003eMucinous\u003c/p\u003e\n \u003cp\u003eEndometroid\u003c/p\u003e\n \u003cp\u003eClear Cell\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26(57.8)\u003c/p\u003e\n \u003cp\u003e6(13.3)\u003c/p\u003e\n \u003cp\u003e7(15.6)\u003c/p\u003e\n \u003cp\u003e4(8.9)\u003c/p\u003e\n \u003cp\u003e2(4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17(81)\u003c/p\u003e\n \u003cp\u003e2(9.5)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e2(9.5)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25(92.6)\u003c/p\u003e\n \u003cp\u003e1(3.7)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1(3.7)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23(95.8)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1(4.2)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2MC\u003c/sup\u003e=24.02\u003c/p\u003e\n \u003cp\u003eP=0.02*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGrade\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14(31.1)\u003c/p\u003e\n \u003cp\u003e31(68.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2(9.5)\u003c/p\u003e\n \u003cp\u003e19(90.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1(3.7)\u003c/p\u003e\n \u003cp\u003e26(96.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e24(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2MC\u003c/sup\u003e=17.01\u003c/p\u003e\n \u003cp\u003eP=0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eI\u003c/p\u003e\n \u003cp\u003eII\u003c/p\u003e\n \u003cp\u003eIII\u003c/p\u003e\n \u003cp\u003eIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27(60)\u003c/p\u003e\n \u003cp\u003e5(11.1)\u003c/p\u003e\n \u003cp\u003e12(26.7)\u003c/p\u003e\n \u003cp\u003e1(2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6(28.6)\u003c/p\u003e\n \u003cp\u003e3(14.3)\u003c/p\u003e\n \u003cp\u003e12(57.1)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7(25.9)\u003c/p\u003e\n \u003cp\u003e4(14.8)\u003c/p\u003e\n \u003cp\u003e13(48.1)\u003c/p\u003e\n \u003cp\u003e3(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1(4.2)\u003c/p\u003e\n \u003cp\u003e2(8.3)\u003c/p\u003e\n \u003cp\u003e17(70.8)\u003c/p\u003e\n \u003cp\u003e4(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2\u003c/sup\u003e=30.38\u003c/p\u003e\n \u003cp\u003eP=0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLN involvement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40(88.9)\u003c/p\u003e\n \u003cp\u003e5(11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15(71.4)\u003c/p\u003e\n \u003cp\u003e6(28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16(59.3)\u003c/p\u003e\n \u003cp\u003e11(40.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11(45.8)\u003c/p\u003e\n \u003cp\u003e13(54.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2\u003c/sup\u003e=15.85\u003c/p\u003e\n \u003cp\u003eP=0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCytology\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28(62.2)\u003c/p\u003e\n \u003cp\u003e17(37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8(38.1)\u003c/p\u003e\n \u003cp\u003e13(61.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10(37.0)\u003c/p\u003e\n \u003cp\u003e17(63.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1(4.2)\u003c/p\u003e\n \u003cp\u003e23(95.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2\u003c/sup\u003e=22.19\u003c/p\u003e\n \u003cp\u003eP=0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePeritoneal involvement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31(68.9)\u003c/p\u003e\n \u003cp\u003e14(31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9(42.9)\u003c/p\u003e\n \u003cp\u003e12(57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12(44.4)\u003c/p\u003e\n \u003cp\u003e15(55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2(8.3)\u003c/p\u003e\n \u003cp\u003e22(91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2\u003c/sup\u003e=23.29\u003c/p\u003e\n \u003cp\u003eP=0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOmental involvement\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31(68.9)\u003c/p\u003e\n \u003cp\u003e14(31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9(42.9)\u003c/p\u003e\n \u003cp\u003e12(57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12(44.4)\u003c/p\u003e\n \u003cp\u003e15(55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2(8.3)\u003c/p\u003e\n \u003cp\u003e22(91.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2\u003c/sup\u003e=23.29\u003c/p\u003e\n \u003cp\u003eP=0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDistant metastasis\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31(68.9)\u003c/p\u003e\n \u003cp\u003e14(31.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11(52.4)\u003c/p\u003e\n \u003cp\u003e10(47.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19(70.4)\u003c/p\u003e\n \u003cp\u003e8(29.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8(33.3)\u003c/p\u003e\n \u003cp\u003e16(66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2\u003c/sup\u003e=10.18\u003c/p\u003e\n \u003cp\u003eP=0.017*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRelapse\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e44(97.8)\u003c/p\u003e\n \u003cp\u003e1(2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e18(85.7)\u003c/p\u003e\n \u003cp\u003e3(14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25(92.6)\u003c/p\u003e\n \u003cp\u003e2(7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6(25)\u003c/p\u003e\n \u003cp\u003e18(75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2MC\u003c/sup\u003e=56.28\u003c/p\u003e\n \u003cp\u003eP=0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of relapse\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eLocal Relapse\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eDistant Mets\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e3(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e2(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2(11.1)\u003c/p\u003e\n \u003cp\u003e16(88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eꭓ\u003csup\u003e2MC\u003c/sup\u003e=0.727\u003c/p\u003e\n \u003cp\u003eP=0.867\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDeath\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e6(25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003eꭓ\u003csup\u003e2MC\u003c/sup\u003e=24.51\u003c/p\u003e\n \u003cp\u003eP=0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eꭓ\u003csup\u003e2\u003c/sup\u003e=Chi-Square test, MC: Monte Carlo test, *statistically significant\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData are expressed as number (%)\u003c/p\u003e\n\u003cp\u003eThe cohort had a median disease-free survival (DFS) duration of 74.68 months (95% CI:69.85\u0026ndash;79.52). The DFS rate was 90.6% at 1 year, 87.2% at 2 years, and 80.3% at 3 years. The survival curve shows a gradual decline over time, with most patients remaining disease-free during the follow-up period. Censoring is frequent in later months, indicating a high proportion of patients remained disease-free.\u003c/p\u003e\n\u003cp\u003eDisease-free survival (DFS) was closely linked to CD24 expression levels, with high CD24 expression associated with a marked reduction in DFS\u003cstrong\u003e\u0026nbsp;(\u003cstrong\u003e31.50 months)\u003c/strong\u003e\u003c/strong\u003e, characterized by a sharp early decline in survival probability. In contrast, patients with negative CD24 expression displayed the most favorable DFS (\u003cstrong\u003e86.31 months)\u003c/strong\u003e, maintaining stable survival over the follow-up period (Figure 5). These results highlight high CD24 expression as an independent predictor of poor DFS and early recurrence, suggesting its potential as a crucial biomarker for prognosis.\u003c/p\u003e\n\u003cp\u003eThe Cox regression analysis identifying several key predictors of disease-free survival (DFS) including age, stage, lymph node involvement, positive cytology, peritoneal-omental involvement, distant metastasis at time of diagnosis and CD 24 expression. \u0026nbsp;High CD24 expression is particularly striking, with an HR of 48.06 (95% CI 6.38-300.56, p=0.001), indicating a very high risk of disease recurrence in patients with elevated CD24 levels. \u003cstrong\u003eThis reinforces high CD24 expression as a crucial independent prognostic marker for disease-free survival. Low and moderate CD24 expression did not reach statistical significance, suggesting a potential dose-response relationship where only high expression is clinically relevant for predicting poor outcomes (\u003c/strong\u003eTable 4).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (4): Cox Regression for Predictors of Disease-Free Survival (DFS)\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;by CD24 Expression Levels\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eamong studied cases\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard Ratio (95%CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD24 Expression Positivity\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative (R)\u003c/p\u003e\n \u003cp\u003ePositive\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003cp\u003e2.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;0.007*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003cp\u003e15.89(2.15-100.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD24 Staining Percentage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003enone\u003c/p\u003e\n \u003cp\u003e1\u0026ndash;40%\u003c/p\u003e\n \u003cp\u003e40\u0026ndash;80%\u003c/p\u003e\n \u003cp\u003e\u0026gt;80%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003cp\u003e1.15\u003c/p\u003e\n \u003cp\u003e3.62\u003c/p\u003e\n \u003cp\u003e3.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.318\u003c/p\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003cp\u003e0.0001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003cp\u003e3.17(0.330-30.47)\u003c/p\u003e\n \u003cp\u003e37.17(4.69-294.67)\u003c/p\u003e\n \u003cp\u003e46.13(5.94-350.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD24 Staining Intensity\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eno staining\u003c/p\u003e\n \u003cp\u003eweak\u003c/p\u003e\n \u003cp\u003emoderate\u003c/p\u003e\n \u003cp\u003eStrong\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003cp\u003e2.01\u003c/p\u003e\n \u003cp\u003e2.87\u003c/p\u003e\n \u003cp\u003e2.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.101\u003c/p\u003e\n \u003cp\u003e0.007*\u003c/p\u003e\n \u003cp\u003e0.005*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 198px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003cp\u003e7.45(0.676-82.17)\u003c/p\u003e\n \u003cp\u003e17.59(2.17-143.09)\u003c/p\u003e\n \u003cp\u003e17.96(2.36-136.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 198px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCD24 Expression Levels\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003cp\u003e1.847\u003c/p\u003e\n \u003cp\u003e1.240\u003c/p\u003e\n \u003cp\u003e3.872\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003cp\u003e0.311\u003c/p\u003e\n \u003cp\u003e0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 198px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eR\u003c/p\u003e\n \u003cp\u003e6.34(0.660-60.95)\u003c/p\u003e\n \u003cp\u003e3.46(0.313-38.11)\u003c/p\u003e\n \u003cp\u003e48.06(6.38-300.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eR: reference group\u003c/p\u003e\n\u003cp\u003eThe median overall survival (OS) for the studied cohort was\u0026nbsp;85.04 months\u0026nbsp;(95% CI: 82.72\u0026ndash;96.80). The 2-year survival rate was\u0026nbsp;97.4%, while the 3-year survival rate was\u0026nbsp;95.7%. The survival curve shows a high overall survival rate for the studied population, with a gradual decline over time. The majority of events appear censored, indicating that a large proportion of patients were still alive at the end of the study period. This reflects relatively favorable outcomes in the early years of follow-up.\u003c/p\u003e\n\u003cp\u003eCD24-positive cases had significantly lower OS than CD24-negative cases (p=0.049), and\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ehigh CD24 expression was significantly associated with OS (p=0.001). High CD24 expression was linked to the shortest survival compared to other expression levels. The survival analysis for patients with high-grade CD24 expression revealed a progressive decline in survival over time. The 2-year survival rate was 87.5%, which dropped to 79.2% at 3 years and further decreased to 73.9% at 4 years (Figure 6).\u003c/p\u003e\n\u003cp\u003eCox\u0026nbsp;regression\u0026nbsp;analysis identified Lymph Node Involvement as an independent predictor of overall survival \u003cstrong\u003e(HR=12.46, p=0.021).\u0026nbsp;\u003c/strong\u003eHigh CD24 expression was associated with a higher risk of death, although the specific hazard ratio could not be fully estimated (undefined), reflecting the significant but complex relationship between CD24 expression and survival outcomes. OS analysis showed a non-significant trend toward worse survival in high CD24 expression cases (p=0.499), suggesting a need for further validation in larger cohorts.\u003c/p\u003e\n\u003cp\u003eThese results emphasize the importance of lymph node involvement and CD24 expression as critical factors in predicting overall survival in ovarian carcinoma. The undefined values for some variables indicate the need for further investigation with larger cohorts to refine the predictive power of the model. Clinically, this emphasizes the multifactorial nature of survival in ovarian cancer and the need to consider multiple prognostic factors when planning treatment.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated the immune-histochemical expression of CD24 in malignant surface epithelial ovarian tumors and its correlation with clinic-pathological parameters and patient outcomes. The findings indicated a significant link between elevated CD24 expression and advanced tumor stage, high-grade tumors, increased lymph node involvement, peritoneal and omental metastasis, and poor survival outcomes. Patients showing elevated CD24 levels had notably reduced disease-free survival (DFS) and overall survival (OS) compared to patients with low or negative expression.\u003c/p\u003e \u003cp\u003eThese findings align with the broader understanding that CD24 functions as an oncogenic driver in various malignancies, playing a crucial role in tumor aggressiveness by promoting epithelial-mesenchymal transition (EMT), immune evasion, and metastatic potential [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe statistical significance observed in this study strengthens the hypothesis that CD24 is not merely an incidental marker but a potential contributor to the aggressive behavior of ovarian tumors. Specifically, our Kaplan-Meier survival analysis and Cox regression models in this study confirmed that CD24 overexpression is an independent predictor of poor prognosis, supporting its role as a valuable prognostic biomarker in ovarian cancer. These results suggest that CD24 expression could be used for patient stratification into different risk categories, potentially guiding treatment decisions.\u003c/p\u003e \u003cp\u003eFurthermore, the strong correlation between CD24 expression and increased metastatic spread suggests that CD24 is not merely a passive marker but actively contributes to tumor dissemination. Given that CD24 enhances tumor cell adhesion, migration, and immune evasion, its high expression in advanced-stage tumors may drive disease progression and chemoresistance as stated by Jang et al., 2024 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] and Wang et al., 2023 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe results of this study align with prior research identifying CD24 as a marker of poor prognosis in ovarian cancer and other malignancies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Previous studies have demonstrated that CD24 expression is linked to EMT, tumor invasion, and chemoresistance, which are consistent with our results [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA study by Nakamura et al., 2017 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] found that CD24 expression was significantly associated with high-grade serous ovarian carcinoma (HGSC), advanced-stage disease, and reduced survival outcomes, paralleling our findings. However, our study extends these observations by providing detailed statistical evidence linking CD24 positivity to DFS and OS, further validating its prognostic significance.\u003c/p\u003e \u003cp\u003eAdditionally, CD24 has been widely studied in breast and pancreatic cancers, where it has been implicated in metastatic dissemination and resistance to apoptosis [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In ovarian cancer, CD24 expression correlates with chemotherapy resistance, which underscores its potential as a therapeutic target [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. This study reinforces these findings by showing that patients with CD24-positive tumors exhibited significantly reduced DFS and OS, highlighting its impact on ovarian cancer progression. Furthermore, the overrepresentation of CD24-positive tumors in high-grade and late-stage disease strengthens the argument that CD24 contributes to tumor progression rather than being an incidental byproduct of malignancy.\u003c/p\u003e \u003cp\u003eThese findings reinforce CD24\u0026rsquo;s potential as a prognostic biomarker. Given its strong association with adverse survival outcomes, CD24 assessment could be integrated into routine histopathological evaluations to improve patient risk stratification. Moreover, CD24-targeted therapies, such as monoclonal antibodies and immune checkpoint inhibitors, are currently under investigation and could offer new therapeutic strategies for ovarian cancer [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study\u0026rsquo;s strengths lie in its robust methodology and clinical relevance, utilizing a well-defined cohort of 117 ovarian cancer cases, ensuring a statistically meaningful analysis. The standardized immunohistochemical protocols and validated scoring criteria minimized interobserver variability, while Kaplan-Meier survival curves and Cox regression models provided a comprehensive evaluation of CD24\u0026rsquo;s prognostic significance.\u003c/p\u003e \u003cp\u003eBy correlating CD24 expression with survival outcomes, the study bridges basic science and translational research, reinforcing its potential as a biomarker for risk stratification and personalized treatment. However, limitations include its retrospective design and single-center setting, which may limit generalizability.\u003c/p\u003e \u003cp\u003eAdditionally, the lack of functional assays prevents a mechanistic understanding of CD24 role in ovarian cancer progression, and variability in treatment regimens introduces potential confounders. Confounding factors such as genetic variations and treatment responses were not fully accounted for in the statistical models, which could influence the observed associations. Future studies should incorporate comprehensive genomic profiling and prospective validation cohorts to strengthen the clinical relevance of these findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this study highlights the significant association between CD24 expression and poor clinical outcomes in ovarian cancer. High CD24 expression correlates with advanced tumor stage, high-grade tumors, increased metastasis, and reduced survival rates, reinforcing its role as a prognostic biomarker. Routine assessment of CD24 expression in ovarian cancer histopathology may enhance patient risk stratification, guiding both prognosis and therapeutic decisions. Future studies should aim to confirm these results in larger patient groups and investigate potential therapeutic approaches directed at CD24 to improve ovarian cancer management and patient survival outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e1. \u003cstrong\u003eCD24\u0026nbsp;\u003c/strong\u003e- Cluster of Differentiation 24\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2. \u003cstrong\u003eCSC\u0026nbsp;\u003c/strong\u003e- Cancer Stem Cells\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e3. \u003cstrong\u003eEMT\u0026nbsp;\u003c/strong\u003e- Epithelial-Mesenchymal Transition\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e4. \u003cstrong\u003eFFPE\u0026nbsp;\u003c/strong\u003e- Formalin-Fixed, Paraffin-Embedded\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5. \u003cstrong\u003eIHC\u0026nbsp;\u003c/strong\u003e- Immunohistochemistry\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e6. \u003cstrong\u003eHGSC\u0026nbsp;\u003c/strong\u003e- High-Grade Serous Carcinoma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e7. \u003cstrong\u003eLGSC\u0026nbsp;\u003c/strong\u003e- Low-Grade Serous Carcinoma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e8. \u003cstrong\u003eFIGO\u0026nbsp;\u003c/strong\u003e- International Federation of Gynecology and Obstetrics\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e9. \u003cstrong\u003eDFS\u0026nbsp;\u003c/strong\u003e- Disease-Free Survival\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e10. \u003cstrong\u003eOS\u0026nbsp;\u003c/strong\u003e- Overall Survival\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e11. \u003cstrong\u003e3YS\u0026nbsp;\u003c/strong\u003e- 3-Year Survival\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e12. \u003cstrong\u003eHR\u0026nbsp;\u003c/strong\u003e- Hazard Ratio\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e13. \u003cstrong\u003eCI\u0026nbsp;\u003c/strong\u003e- Confidence Interval\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e14. \u003cstrong\u003eLN\u0026nbsp;\u003c/strong\u003e- Lymph Node\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e15. \u003cstrong\u003eMC\u0026nbsp;\u003c/strong\u003e- Monte Carlo\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e16. \u003cstrong\u003eR\u0026nbsp;\u003c/strong\u003e- Reference group\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eEthics Approval and Consent to participate\u003c/strong\u003e \u003cp\u003eThis research received ethical approval from the Institutional Research Board (IRB) of the University Faculty of Medicine (Code Number: MDP.21.07.71, 2021). Confidentiality was maintained by using pathology identification numbers instead of patient names. The study complied with the latest revision of the Helsinki Declaration on ethical guidelines for medical research involving human subjects (The World Medical Association, 2013). After completion, all paraffin tissue blocks were returned to the archives to allow potential future use for clinical or research purposes.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent For Publication\u003c/strong\u003e \u003cp\u003eThe authors unanimously agree to publish the data and information in the manuscript.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003e\u0026bull; G. A. A.: Conceptualization, Methodology, Data analysis, Manuscript drafting.\u0026bull; N. A.: Supervision, Critical review, Methodology guidance.\u0026bull; M. A. M.: Literature review, Methodological oversight, Manuscript revision.\u0026bull; A. E.: Literature review, Statistical Analysis.\u0026bull; M. M. A. F. Z.: Literature review, Data validation, Manuscript editing.AcknowledgmentsThe authors acknowledge the Pathology Department, Faculty of Medicine, Mansoura University, for providing resources and facilities for this study.FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors acknowledge the Pathology Department, Faculty of Medicine, Mansoura University, for providing resources and facilities for this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and analyzed during this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLheureux S, Gourley C, Vergote I\u003cem\u003e, et al.\u003c/em\u003e Epithelial ovarian cancer. Lancet (London, England). 2019;393(10177):1240-53.\u003c/li\u003e\n\u003cli\u003ePeres LC, Cushing-Haugen KL, K\u0026ouml;bel M\u003cem\u003e, et al.\u003c/em\u003e Invasive Epithelial Ovarian Cancer Survival by Histotype and Disease Stage. Journal of the National Cancer Institute. 2019;111(1):60-8.\u003c/li\u003e\n\u003cli\u003eRomani C, Capoferri D, Grillo E\u003cem\u003e, et al.\u003c/em\u003e The Claudin-Low Subtype of High-Grade Serous Ovarian Carcinoma Exhibits Stem Cell Features. Cancers. 2021;13(4).\u003c/li\u003e\n\u003cli\u003eSiegel RL, Miller KD, Wagle NS\u003cem\u003e, et al.\u003c/em\u003e Cancer statistics, 2023. CA: a cancer journal for clinicians. 2023;73(1):17-48.\u003c/li\u003e\n\u003cli\u003eCasey L, Khan MYA. Serous Tumors of the Ovary. In: van Krieken JHJM, editor. Encyclopedia of Pathology. Cham: Springer International Publishing; 2020. p. 1-12.\u003c/li\u003e\n\u003cli\u003eMotohara T, Yoshida GJ, Katabuchi H. The hallmarks of ovarian cancer stem cells and niches: Exploring their harmonious interplay in therapy resistance. Seminars in cancer biology. 2021;77:182-93.\u003c/li\u003e\n\u003cli\u003eNakamura K, Terai Y, Tanabe A\u003cem\u003e, et al.\u003c/em\u003e CD24 expression is a marker for predicting clinical outcome and regulates the epithelial-mesenchymal transition in ovarian cancer via both the Akt and ERK pathways. Oncology reports. 2017;37(6):3189-200.\u003c/li\u003e\n\u003cli\u003eZhao K, Wu C, Li X\u003cem\u003e, et al.\u003c/em\u003e From mechanism to therapy: the journey of CD24 in cancer. Frontiers in immunology. 2024;15:1401528.\u003c/li\u003e\n\u003cli\u003eLanden CN, Jr., Goodman B, Katre AA\u003cem\u003e, et al.\u003c/em\u003e Targeting aldehyde dehydrogenase cancer stem cells in ovarian cancer. Molecular cancer therapeutics. 2010;9(12):3186-99.\u003c/li\u003e\n\u003cli\u003eChen GY, Tang J, Zheng P\u003cem\u003e, et al.\u003c/em\u003e CD24 and Siglec-10 selectively repress tissue damage-induced immune responses. Science (New York, NY). 2009;323(5922):1722-5.\u003c/li\u003e\n\u003cli\u003eKleinmanns K, Fosse V, Bj\u0026oslash;rge L\u003cem\u003e, et al.\u003c/em\u003e The Emerging Role of CD24 in Cancer Theranostics-A Novel Target for Fluorescence Image-Guided Surgery in Ovarian Cancer and Beyond. Journal of personalized medicine. 2020;10(4).\u003c/li\u003e\n\u003cli\u003eAssociation WM. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013;310(20):2191-4.\u003c/li\u003e\n\u003cli\u003eMalpica A, Deavers MT, Lu K\u003cem\u003e, et al.\u003c/em\u003e Grading ovarian serous carcinoma using a two-tier system. The American journal of surgical pathology. 2004;28(4):496-504.\u003c/li\u003e\n\u003cli\u003eBerek JS, Renz M, Kehoe S\u003cem\u003e, et al.\u003c/em\u003e Cancer of the ovary, fallopian tube, and peritoneum: 2021 update. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. 2021;155 Suppl 1(Suppl 1):61-85.\u003c/li\u003e\n\u003cli\u003eNagare RP, Sneha S, Sidhanth C\u003cem\u003e, et al.\u003c/em\u003e Expression of cancer stem cell markers CD24, EPHA1 and CD9 and their correlation with clinical outcome in epithelial ovarian tumours. Cancer biomarkers : section A of Disease markers. 2020;28(3):397-408.\u003c/li\u003e\n\u003cli\u003eGu Y, Zhou G, Tang X\u003cem\u003e, et al.\u003c/em\u003e The biological roles of CD24 in ovarian cancer: old story, but new tales. Frontiers in immunology. 2023;14:1183285.\u003c/li\u003e\n\u003cli\u003eJang Y, Kang S, Han HH\u003cem\u003e, et al.\u003c/em\u003e CD24 induced cellular quiescence-like state and chemoresistance in ovarian cancer cells via miR-130a/301a-dependent CDK19 downregulation. Cell Death Discovery. 2024;10(1):81.\u003c/li\u003e\n\u003cli\u003eGu Y, Zhou G, Tang X\u003cem\u003e, et al.\u003c/em\u003e The biological roles of CD24 in ovarian cancer: old story, but new tales. Frontiers in immunology. 2023;14.\u003c/li\u003e\n\u003cli\u003eKim S, Park JM, Park S\u003cem\u003e, et al.\u003c/em\u003e Suppression of TNBC metastasis by doxazosin, a novel dual inhibitor of c-MET/EGFR. Journal of Experimental \u0026amp; Clinical Cancer Research. 2023;42(1):292.\u003c/li\u003e\n\u003cli\u003eFang X, Zheng P, Tang J\u003cem\u003e, et al.\u003c/em\u003e CD24: from A to Z. Cellular \u0026amp; molecular immunology. 2010;7(2):100-3.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ovarian cancer, Surface epithelial tumors, CD24, Intratumoral heterogeneity, Cancer stem cells (CSCs)","lastPublishedDoi":"10.21203/rs.3.rs-6235263/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6235263/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSurface epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy, mainly due to late-stage diagnosis and therapeutic resistance. Intratumoral heterogeneity, driven by cancer stem cells (CSCs), contributes to metastasis, recurrence, and therapy resistance. Cluster of Differentiation 24 (CD24) has emerged as a promising biomarker linked to tumor progression, metastasis, and immune evasion, but further research is needed to understand its role in ovarian cancer progression and patient outcomes.\u003c/p\u003e\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eThis study investigates the immunohistochemical expression of CD24 in malignant surface epithelial ovarian tumors and its correlation with clinicopathological parameters and patient outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe performed a retrospective cohort analysis involving 117 formalin-fixed, paraffin-embedded (FFPE) samples of malignant ovarian surface epithelial tumors, retrieved from the archives of the Surgical Pathology Laboratory at our University oncology center in the period between 2018 and 2021. Patients underwent surgical resection, with follow-up data collected until 2024. Immunohistochemical (IHC) staining for CD24 was performed, and expression levels were assessed based on staining percentage and intensity. The correlation between CD24 expression and clinicopathological factors, disease-free survival (DFS), and overall survival (OS) was analyzed using appropriate statistical methods, including Kaplan-Meier survival analysis and Cox regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eCD24 expression was observed in 61.5% of cases, with varying expression levels: low (17.9%), moderate (23.1%), and high (20.5%). High CD24 expression was predominantly observed in HGSC (p\u0026thinsp;=\u0026thinsp;0.02) and was significantly associated with advanced FIGO stage (p\u0026thinsp;=\u0026thinsp;0.001), high tumor grade (p\u0026thinsp;=\u0026thinsp;0.001), lymph node involvement (p\u0026thinsp;=\u0026thinsp;0.001), positive peritoneal cytology (p\u0026thinsp;=\u0026thinsp;0.001), and distant metastases (p\u0026thinsp;=\u0026thinsp;0.085). Survival analysis revealed that patients with high CD24 expression exhibited significantly shorter DFS (p\u0026thinsp;=\u0026thinsp;0.001) and a non-significant trend toward reduced OS (p\u0026thinsp;=\u0026thinsp;0.499), compared to those with lower or absent expression. Cox regression identified CD24 as an independent predictor of poor prognosis, alongside age, tumor stage, and lymph node involvement.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eCD24 overexpression in surface epithelial ovarian cancer is strongly correlated with aggressive tumor behavior, advanced stage, and poor survival outcomes. These findings support the incorporation of CD24 expression into risk stratification models and highlight the potential of CD24-targeted therapies to improve ovarian cancer outcomes.\u003c/p\u003e","manuscriptTitle":"Immunohistochemical Expression of CD24 and Its Correlation with Clinicopathological Features in Malignant Surface Epithelial Tumors of the Ovary","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 11:12:42","doi":"10.21203/rs.3.rs-6235263/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7ea2a67b-fdab-44be-b6d4-7b0e3e626076","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-26T08:09:51+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-31 11:12:42","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6235263","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6235263","identity":"rs-6235263","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}