Expression And Clinical Significance Of Ub And Cyclinb1 In Epithelial Ovarian Tumors

Background and Objective:The epithelial ovarian cancer is one of three kinds of malignant tumors in female genital system. Because most patients are asymptomatic until the disease has metastasized, they are diagnosed in advanced stages, with five years survival rates of 30%～40%. The disease continues to be the leading cause of death from gynecological cancers. Currently, the only sensitive tumor marker that has been well-defined and validated role in the management of ovarian cancer is CA₁₂₅, which can be detected in the serum of 80% of women with ovarian carcinoma. However, CA₁₂₅ is robust only in following response to treatment or progression of the disease because it lacks specificity. Thus, there is an urgent need for additional diagnostic and prognostic markers with high specificity for this disease. It is an important subject to find new biomarkers which can be used for early detection,monitering prognosis to elevate the survival rates of patients with ovarian cancer recently.Ubiquitin(Ub )and Ubiquitin-proteasomepathway(UPP), play a great role in the occurrence and development of tumor, ub is a highly conservative polypeptide existing in all eukaryote histiocyte, and it subsists in the form of free molecule and ubiquitous-bindin(protein-Ubation). It distributes in all kinds of tissue widely, and it is a component participating in post-translational modification of paraprotein, aiming to degrade the protein. Under the catalysis of the functional Ub ligase system, which is an enzyme specifically dependent on ATP, all sorts of cell protein are modified by uniquitination, furthermore, with the attendance of lososome and non-lososome system, uniquitinic protein is degraded, if UPP is obstructed, it will have an effect on the modulation of cell cycle, not only can increase the process of oncogene, but also decrease the action of anti-oncogene, so that it can raise the occurrence of tumor. Therefore, it is very important for lots of cells to have a modification of uniquitin, such as the selective degradation of intracellular protein, the stress reaction against all destructive stimulus, the protective reaction for cell trauma and so on. So if there is an abnormal Ub expression in oophoroma and whether there is an influence of its change to the occurrence, development and prognosis of oophoroma are not very clear.The occurrence, development and transformation of tumor are directly bound up with the regulational imbalance of cell cycle.CyclinB1 which is a typical division-cyclin,participates in the regulation of cell cyclin checkpoint and promotes the transition of G₂ stage to M stage and finally accelerates the process of cell cycle. SO far, Six subsets of type B cell cyclin have been discovered in mammal , namely CyclinB1-6. CyclinB1 mainly appears in S stage and starts to express in this period, what is more,it reaches the peak point at the stage of G₂/M and it is degraded swiftly by Ubation. The excessive expression of CyclinB1, which shortens the transition time of cell cycle from G₂ stage to M one, induced cell transformation.To investigate the expression of Ub and CyclinB1 protein in ovarian epithelial carcinomas and its clinical significance, we used immunohistochemistry to analyze the relationship of the expression with its clinical pathological character and survival of patients with ovarian epithelial carcinomas. We want to reveal the role of Ub and CyclinB1 in the growth and progression of ovarian carcinomas, and supply scientific date and theoveticac evidence for studying its biological function.Materials and Methods1 Paraffin imbedded 70 ovarian epithelial tumors and 20 hysteromyoma were collected with pathological and clinical integrity data , including all patients were operated at the Department of Gynecology, the First Affiliated Hospital of Zheng zhou University from January 2004 to December 2008. No radiotherapy, chemotherapy or other therapy were performent before operation. 50 malignant ovarian tumors (include 36 serous cystadenocarcinoma, 9 mucous cystadeno carcinoma, 5 endometrioid carcinoma), 20 benign ovarian tumors (include 16serous cystadenoma, 4 mucous cystadenoma).2 Immunohistochemistry was used to detect the expression of Ub and CyclinB1 in 20 cases of normal ovarian tissue , 20 cases of benign ovarian tumor and 50 cases of primary epithelial ovarian cancer . The relationships with histological type pathological grading, clinical staging and lymphatic metastasis were analyzed.3 All data were analyzed by the SPSS statistical package program 13.0. Discussing relationship between their expression and clinical-pathological factors by Chi-Square Test, their relationship by Spearman. Statistically significant level was considered as "alpha equals 0.05" (a =0.05).Results1 The positive rate of Ub protein expression in epithelial ovarian carcinomas and benign ovarian epithelial tumors and normal ovaries were 34%,10%,5% respectively. The positive rate of CyclinB1 protein expression in epithelial ovarian carcinomas and benign ovarian epithelial rumors and normal ovaries were 42%, 15%, 5% respectively. The expression of Ub and CyclinB1 protein in ovarian epithelial carcinomas was significantly higher than that in normal ovaries and benign ovarian epithelial tumors (P<0.01).2 The expression of Ub protein in ovarian epithelial carcinomas was significantly associated with histological grade, FIGO stage and lymph node metastases (P<0.05) and was not significantly associated with the patients' histological subtype (P>0.05). The positive rate of Ub protein expression in tissues withⅢ,Ⅳstage was significant higher than that ofⅠ,Ⅱstage (χ²=4.529; P<0.05); The positive rate of Ub protein expression in G₁,G₂ grade tissues was significantly higher than that of G₃ grade tissues (χ²=3.964, P<0.05); the positive rate of Ub protein expression in tissue with lymphoid node metastasis was significant higher than that of tissues without lymphoid node metastasis (χ²=6.269, P<0.05).3 The expression of CyclinB1 protein in ovarian epithelial carcinomas was significantly associated with the patients' histological grade, FIGO stage and lymph node metastases (P<0.05); wasn't significantly associated with the patients' histological subtype (P>0.05). The positive rate of CyclinB1 protein expression in tissues withⅢ,Ⅳstage was significantly higher than that ofⅠ,Ⅱstage (χ²=5.520, P<0.05); the positive rate of CyclinB1 protein expression in G₃ grade tissues was significantly higher than that of G₁,G₂ grade (χ²=4.217, P<0.05); the positive rate of K.LK15 protein expression in tissues with lymphoid node metastasis was significantly higher than that of without lymphoid node metastasis (χ²=6.226, P<0.05).4 The correlation between the expression of Ub and CyclinB1 protein in ovarian epithelial carcinomas was analyzed. Their expression which were all positive or negative were respectively 7 cases and 19 cases. The expression of Ub was positive with negative expression of CyclinB1 were 10 cases. The expression of CyclinB1 was positive with negative expression of Ub were 14 cases. There was positively correlation between the expression of Ub and CyclinB1 protein in ovarian epithelial carcinomas (r =0.301, P=0.033).Conclusions1 Ub and CyclinB1 protein showed high expression in ovarian epithelial carcinomas, while showed low expression in benign ovarian epithelial tumors and normal ovaries. There was a close relationship between the positive rate of Ub and CyclinB1 with surgical- pathological stages, histological differentiation and lymph node metastasis. It suggested that Ub and yclinB1 might play an important role in the, development and metastasis of ovarian epithelial carcinomas.2 The expression of Ub protein was correlated with that of CyclinB1 protein in ovarian epithelial carcinomas, implying that Ub may cooperate with CyclinB1 in ovarian epithelial carcingenclis. It might provide a new management to treat ovarian epithelial carcinoma in the future.3 Detecting the expression level of Ub and CyclinB1 might have important significance in judging malignant degree of ovarian epithelial carcinoma .