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Abstract Ovarian tumors include different groups of tumors. They are classified into: epithelial, germ cell, and sex cord stromal tumors. Epithelial tumors are further subclassified into benign, borderline, and malignant tumors. Ovarian cancer is the seventh cancer in women worldwide Epithelial ovarian cancers are the most common type of ovarian cancers accounting for 90% of all cases. Borderline ovarian tumors (BOT) constitute about 10%–15% of ovarian tumors. The distinction of borderline ovarian tumors from malignant tumors can be challenging in some cases.. Stratification of ovarian tumors into benign, borderline, or malignant is critically important regarding the prognosis, outcome, the extension of surgery and further follow up. EMT is suggested to be a major process for the conversion of early stage ovarian tumors to invasive and metastatic malignancies, due to the loss of epithelial characteristics and acquisition of mesenchymal characteristics. EMT is generally induced by developmental signalling pathways, leading to the molecular changes, including the loss of epithelial markers, such as E-cadherin, and the upregulation of mesenchymal markers. MDM2 is an oncogene related with various types of malignances, including the occurrence of metastasis in several reports. MDM2 facilitates cell motility, invasivness and EMT occurrence in ovarian cells by regulating E-cadherin ubiquitination and degradation through the activation of TGF-b-Smads pathway. E-cadherin is a member of the cadherin superfamily, a group of cell surface glycoproteins that mediate cellular adhesion. E-cadherin allows the junction between the cell and its cellular environment. Its deficiency allows the cells to detach from the tumor site and give the cells an invasive phenotype. E-cadherin was considered a tumor suppressor, since it was found to be downregulated in malignant epithelial tumors. The present work aimed at determining the expression of murine double minute-2 (MDM2) and E-cadherin in epithelial ovarian tumors .In addition, evaluating their value in differentiating borderline from malignant and benign epithelial ovarian tumors. The present study included 70 paraffin blocks of ovarian tumors. That was recovered retrospectively from the archive of the pathology department, Medical Research Institute, Gamal Abd El Naser Hospital, and some private labs between the years 2015 to 2020.10 cases were of benign ovarian tumors, 30 cases of borderline ovarian tumors and 30 cases of malignant epithelial ovarian tumors. According to the result of the present study MDM2 was shown to be more frequently expressed in malignant epithelial ovarian tumors than in borderline and benign tumors with statistically significant difference. Summary, conclusion & Recommendations 95 On the other hands E-cadherin expression was more preserved in benign tumors with homogenous staining pattern, while decreased expression was seen in borderline and malignant epithelial ovarian tumors. Most of malignant ovarian tumors have heterogenous staining pattern. The borderline ovarian tumors lie in between benign and malignant groups as regards E-cadherin pattern. According to E-cadherin intensity and pattern of expression EMT status was noted to be more evident in borderline and malignant epithelial ovarian tumors than benign ones with statistically significant difference. Loss of E-cadherin expression was statistically significantly related to the presence of omental deposits, high grade, and laterality in malignant ovarian tumors. MDM2 was shown to be the most important marker to diagnose malignant from borderline ovarian tumors. The presence of (MDM2+/ E- cadherin -/ EMT status +) combination or (MDM2+/ EMT status +) even with preserved E-cadherin were shown to be reliable combinations associated with borderline and malignant ovarian tumors in contrast to benign ovarian tumors. |