الفهرس 
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Abstract
In Egypt, malignant ovarian tumors represented 40.7% of female genital tract malignancies(El Bolkainy et al., 2013a) and malignant ovarian surface epithelial tumors account for 73.33% of them (Mokhtar et al., 2007). Worldwide, ovarian cancer (OC) is the sixth most common cancer in women (Boyle and Levin, 2008). It is the most frequent cause of death due to gynecologic cancer (Seidman et al., 2011). This study included 89 ovarian tumors from Egyptian patients, collected from Pathology Department, Faculty of Medicine, Menofia University and private labs during the period between January 2010 and January 2015. The studied cases included benign cystadenoma (16 cases), borderline cystadenoma (19 cases) and malignant adenocarcinoma (54 cases). In the present study, dual comparison between borderline and malignant cases as regards clinicopathological features revealed that all borderline cases were belonging to T1 & early FIGO stage grouping (p=0.000). Surface epithelial tumors are no longer considered as a single disease but are divided into types I and II on the basis of their molecular features, cell of origin, and theirbehavior (Kurman, 2013). Comparison between type I and type II carcinoma cases as regards clinicopathological features revealed that type II showed a significant association with with solid or mixed cut section (p=0.02), serous carcinoma (p=0.000), presence of vascular invasion (p=0.04), presence of necrosis (p=0.05), presence of macroscopic omental nodule (p=0.05) and high mitotic count (p=0.000). Moreover, Type II carcinoma showed significant association with advanced T3 (p=0.008), FIGO III stage (p=0.01) and with high grade (p=0.04). Hypoxia inducible factor 1 (HIF1) is a key regulator of cellular responses to hypoxia. It targets the genes involved in tumor cell energy metabolism, angiogenesis, tumor metastasis, ion metabolism and catecholamine metabolism, thereby influencing the expression of proteins, including erythropoietin, vascular endothelial growth factor, glucose transporter-1 (GLUT-1), glyceraldehyde 3-phosphate dehydrogenase, inducible nitric oxide synthase, insulin-like growth factor-2, tyrosine hydroxylase and glycolytic enzymes. HIF-1α and GLUT-1 are the intrinsic hypoxia markers that have been studied the most in various tumors (Wu et al., 2013b). Therefore, this work was planned to investigate the expression of HIF1alpha and GLUT-1 in benign, borderline and maliganant ovarian surface epithelial tumors by immunohistochemical (IHC) staining technique, and to correlate their expression with the available clinicopathological features. Positive HIF1 alpha staining was considered when cytoplasmic brown staining was seen. While GLUT-1 staining was considered positive when cytoplasmic or mebranocytoplasmic brown staining was noticed. As regards to HIF1 alpha, 37.5% of benign, 89.5% of borderline and 81.5% of malignant cases were positive. HIF1 alpha showed significant gradual increase from benign to malignant to borderline groups in all studied cases (p=0.006), more in type I than in type II with no significance. HIF1 alpha was also expressed in stroma of cases and there was positive significant correlation between H-score of HIF1 alpha expression in tumor cells and stroma of borderline and malignant cases. Comparing the expression of HIF1 alpha and different clinicopathological parameters in total malignant cases revealed the significant association between HIF1 alpha expression and unilaterality (p=0.008), intact capsule (p=0.01), absence of uterine implant (p=0.01), low grade tumors (P=0.05) and absence of distant metastasis (0.01). This was compatible with good prognostic impact of HIF1alpha marker in ovarian tumors. High expression of GLUT-1 was observed in 87.5% of benign, 100% of borderline and 100% of malignant cases. GLUT-1 median H score was significantly higher in malignant compared to benign cases (p = 0.000). Higher in type II than in type I with no significant difference. Comparing the expression of GLUT-1 and different clinicopathological parameters in total malignant cases revealed the significant association between GLUT-1 expression and bilaterality (P=0.004), solid or mixed cut section (p=0.03), presence of vascular invasion (p=0.05), presence of gross and microscopic omental nodule (p=0.003 and 0.001) which important indicators in tumor staging also intense GLUT1 significant associated with T3 stage (p=0.01) and high FIGO stage III (p=0.01). These were compatible with poor prognostic features of ovarian carcinoma. Comparison between HIF1 alpha and GLUT-1 in malignant cases revealed a significantly association as regards to their expression (p=0.001), but no significant correlation between both markers was detected.The HIF system arises as a molecular target in the treatment of ovarian carcinoma. This may supply a promising target for tumor antiangiogenesis therapy and prevention of metastatic progression and invasion in EOC.