Study On Expression Of IEX-1 In Ovarian Epithelial Tumor And Its Relationship With Apoptosis

Background and PurposeOvarian cancer is one of the female genital system malignant tumors affecting women health, Among gynecological malignancies, ovarian cancer is the leading cause of death. Owing to the nonspecific clinical symptoms and the insidious evolution, more than 70% of ovarian cancer is diagnosed at a late stage. Therefore, the prognosis of ovarian cancer patients is poor and the survival rate of five years is about 25%-30%. Factors involved in biological behavior of ovarian cancers are considered to be of great importance in this disease. Recent study showed significant correlation between the negative IEX-1 expression and malignant behavior in ovarian tumors. The disordered regulatory mechanism of apoptosis plays an important role in the development of malignant tumors. Cell apoptosis is an active process of cell death controlled by genes and a basic physiological mechanism. It plays an important role in pathological processes of diseases and has great biological significance. Apoptosis is generally defined as a genetic program of cellular suicide with unique biochemical and morphological characteristics. The disordered regulatory mechanism of apoptosis plays an important role in the development of malignant tumors. The core of tumor treatment is to promote tumor cell apoptosis or restrain proliferation.IEX-1 is a stress-inducible protein involved in the regulation of cell-cycle progression and apoptosis, whose expression can be rapidly activated and has a role in regulating early cell growth. The promoter of the IEX-1 gene contains consensus sequences for various transcription factors, including P53,c-Myc,NF-KB/re,and Bcl-2. These multiple transcription factors have been reported to regulate cell-cycle progression and apoptosis. But, IEX-1 promotes or inhibits cell-cycle progression and apoptosis depending on the cell type-specific stimulation. Several studies have shown that IEX-1 may function as a pro-apoptotic factor in tumor cells and thereby limiting the tumor progression. Therefore, loss of IEX-1 expression may prevent apoptosis leading to a state of uncontrolled increase in a malignant cell mass. IEX-1 is associated to the occurrence and development of tumor, Evaluation of IEX-1 expression may be clinically helpful for selecting an appropriate treatment strategy for patients with ovarian tumor. The aim of this study was to investigate the expression of IEX-1 protein in ovarian tumors using S-P immunohistochemistry, and explore its role in the occurrence and development of ovarian carcer. The apoptotic rate (AI) of tumor cells was determined in terminal deoxynucleotide transferase mediated UTP nick end labeling (TUNEL), and explored apoptotic role in the occurrence and development of ovarian carcinoma. The relation between IEX-1 protein expression and apoptosis was also examined, which is useful to clinical diagnosis and therapy.Materials and MethodsOne hundred and five cases of ovarian tumors samples were obtained from the Department of Gynecology and Obestetrics, the first affiliated and the third hospital of Zhengzhou University which included 21 cystadenomas,24 borderline tumors, 60 epithelial ovarian cancer tissue (serous adenocarcinoma 48, mucinous adenocar-cinoma 8,others adenocarcinoma 4), These tumors were examined for the expression of IEX-1 protein by immunohistocehmical staining method. The apoptosis of tumor cells was determined in terminal deoxynucleotide transferase mediated UTP nick end labeling (TUNEL), The apoptotic index=(apototic cells/1000)×100%.Results 1 Expression of IEX-1 protein was found in 38.3%(23/60) ovarian cancer,62.5% (15/24) in borderline tumors,80.9%(16/21) in cystadenomas (P=0.004).2 The expression of IEX-1 was significantly associated with FIGO stage and histological grade (P<0.05), but not with age(P=0.976), histological type (P= 0.481).3 The cell apoptosis rate (AI) in ovarian cancer was found as (5.20±5.78)<(15.68±12.63) in borderline tumors and<(26.82±17.77) in cystadenomas. The cell apoptosis rate was significantly lower in ovarian cancer compared to cystadenomas and borderline tumors (P<0.05).4 The correlation between IEX-1 and AI was significant. with correlation coefficient was rs=0.551(P=0.010)in ovarian cystadenomas; rs=0.548 (P<0.01) in borderline tumors andrs=0.861(P<0.01)in ovarian cancer.Conclusions1 Expression of IEX-1 is significantly reduced in malignant ovarian tumors.The high expression of IEX-1 in benign ovarian tumors and the low expression in malignant ovarian tumors indicate its role in progression of epithelial ovarian tumors.2 In ovarian epithelial tumors, the expression of IEX-1 is positively correlated with apoptosis. The tumors with high expression of IEX-1 have significant apoptosis indicating that IEX-1 may promote tumor cells apoptosis. Thus, the assessment of IEX-1 and apoptosis might be a guide for the diagnosis for ovarian tumors.