Expression and Their Significance of Apoptosis Regulatory Factors Survivin、XIAP and c-Jun、NF-κB in Epithelial Neoplasm of Ovary
|School||Zunyi Medical College,|
|Course||Pathology and Pathophysiology|
|Keywords||Apoptosis Apoptotic regulators Transcription factor Benign ovarian tumors Ovarian cancer borderline ovarian tumors Ovarian cancer Immunohistochemistry|
Background and Objective:Imbalance of apoptosis has a closely relationship with the occurrence and development of tumors. Ovarian tumors are common tumors of female genital mutilation, who died of ovarian cancer, accounts for various types of gynecological cancer first, a serious threat to the life of women. XIAP is a known inhibitor of apoptosis protein family which is the strongest member. Expression of XI-AP was low in normal tissue expression, and its expression in a variety of malignant tumors was significantly higher.XIAP may play an important role in the process of cell proliferation and malignant transformation. And Survivin widely expressed in va- rious tumor tissues and human embryonic tissues, and in very few normal tissues, Su-rvivin is another inhibitor of apoptosis protein family, a stronger role in the protein,in- hibits apoptosis and regulation of cell mitosis. XIAP、Survivin inhibits apoptosis both by direct initiation factor effect caspase-9 and caspase-3 and caspase-7 activity.NF-KB is important nuclear transcription factor to regulate cell proliferation and apoptosis. In the resting NF-κB binding to its inhibitory protein IκB present in the cell cytoplasm. Chemotherapy drugs, radiation and other factors under, IκB phosphorylation, ubiquitination, and then be hydrolyzed, NF-κB activation and translocation to the nuclear entry, regulating transcription of target genes. NF-κB has been proposed by scholars and its signaling pathway is a strategy for cancer therapy. AP-1 is a class of immediate early gene encoded by the nuclear transcription factor. Most of the studies that the activation of AP-1 can induce cell proliferation, transformation and carcinogenesis, and regulation by AP-1 downstream target genes for matrix degradation around the tumor, tumor cell adhesion and increased exercise capacity, metastatic tumor angiogenesis, cell irregular periods and other links to promote tumor invasion and metastasis. The expressional relationship between apoptotic regulators XIAP、 Survivin、Caspase-3 and transcription factor AP-1、NF-κBp65、IκB-αin epithelial ovarian tumor has not been reported. In this study, detection the expression and its expressional relationship of XIAP、Survivin、Caspase-3、AP-1(c-Jun)、NF-κBp65、IκB-αin epithelial ovarian cancer, preliminary study these six factors in these ovarian cancer development and the role of contact with clinical cases.Materials and Methods:The study samples were from the Department of Pathology,Affi-liated Hospital of Zunyi Medical College from 2006 to 2009 archive material.Collect betw-een 2006-2009 confirmed 60 cases of ovarian epithelial tumors by pathological examination after surgery.These can be divided into four groups:①. ovarian cancer, primary epithelial ovarian cancer 30 cases, including 3 cases of mucinous cystadenocarcinoma,27 cases of serous adenocarcinoma, stages ofⅠandⅡinclude 21 cases,Ⅲand andⅣ,9 cases.Patients aged 30-75 years, mean age 51.4 years, lymph node metastasis in 2 cases, more than 28 case without lymph node metastasis.②. borderline ovarian tumor group,15 cases of borderline ovarian tumors, including borderline mucinous cystadenoma,10 cases of borderline serous cystadenoma in 5 cases, patients aged 19-62 years, mean age 39.2 years.③. ovarian benign tumor group,15 cases of benign ovarian tumors, serous cystadenoma were patients aged 24-69 years, mean age 39.8 years.④. normal ovarian tissue group, normal ovarian tissues (15 cases, biopsies from ovarian, uterine fibroids or dysfunctional uterine bleeding, uterine prolapse cases underwent hysterectomy without ovarian tissue pathology abnormal) served as contrast. Immunohistochemical SP method and were detected by semi-quantitative inte-gral XIAP, Survivin, Caspase-3, AP-1 (c-jun), NF-KBp65, IκB-a in normal ovarian tissue, benign ovarian tumors, borderline ovarian tumors and expression in ovarian cancer. The data obtained are used SPSS 13.0 statistical software,comparing the the experimental group and control group with positive expression rate use Chi-square Test, all the image analysis results are mean and standard deviation (×±S), the index and clinical pathology relationships betw-een features using t test, correlation between the expression of each index using correlation analysis. When p<0.05, it means that these result have statistically significance.When p< 0.01, it means that these result have notable statistically significance.Results:1. The positive expression rates of apoptosis regulators XIAP in normal ovarian tissue, benign ovarian tumor, borderline ovarian tumors, epithelial ovarian cancer were: 0%,13.3%,20%,73.3%. The positive expression rates of Survivin in normal ovarian tissue, benign ovarian tumor, borderline ovarian tumors, epithelial ovarian cancer were: 0%,13.3%,26.7%,76.7%. The statistical comparison results of regulatory factor XIAP showed that this factor in the malignant group and the normal group (p<0.01), borderline group, benign group, was statistically significant (p<0.05), the junction of group with the benign group, the normal group was no significant difference (p> 0.05). The statistical comparison of Survivin showed that in malignant and normal group (p<0.01), and the borderline group, compared with the benign group, was statistically significant (p<0.05), the junction with the benign group, the difference with normal group Statistically significant (p<0.05), benign and normal group the difference was not statistically significant (p<0.05).The positive expression rates of transcription factor AP-1 (c-jun) in normal ovarian tissue, benign ovarian tumor, borderline ovarian tumors, epithelial ovarian cancer were:26.7%,46.7%,53.3%,86.7%. Statistical comparison of its results showed that ovarian cancer compared with the control group was statistically significant (p<0.01), ovarian cancer and borderline group, benign group was statistically significant (p<0.05), the junction with the benign group group and normal group was not statistically significant (p>0.05), benign and normal group was not statistically significant (p> 0.05). The positive expression rate of Caspase-3 in normal ovarian tissue, benign ovarian tumor, borderline ovarian tumors, epithelial ovarian cancer were 33.3%,46.7%,66.7%,83.3%. The positive expression rates of NF-κBp65 in normal ovarian tissue, benign ovarian tumor, borderline ovarian tumors, epithelial ovarian cancer were:20%,33.3%,46.7%,70%. The positive expression rates IκB-αin normal ovarian tissue, benign ovarian tumor, borderline epithelial ovarian tumors, epithelial ovarian cancer were:26.7%,53.3%,73.3%,80%. The statistical comparison of Caspase-3, transcription factor NF-κBp65 and IκB-αshowed these three factors in the malignant group compared with the normal group was significant (p<0.01), malignant and borderline group, and the benign group, borderline group and the benign group compared with the normal, benign and normal groups were not statistically significant (p> 0.05). 2.Expression of apoptosis regulators XIAP、Survivin、Caspase-3 and transcription factor NF-κBp65 in ovarian cancer tissues were positively correlated with the clinical stage. Expression of XIAP, Survivin and the transcription factor NF-κBp65 in ovarian cancer tissues were positively correlated. Expression of transcription factor AP-1 (c-Jun) and the transcription factor NF-KBp65 in ovarian cancer tissues were positively3.correlated.Expression of IκB-αand NF-KBp65 in ovarian cancer tissues were negatively correlated.Expression of transcription factor IκB-αin ovarian cancer tissues were negatively correlated with the clinical stage.Expression of Transcription factor AP-1 (c-Jun) in ovarian cancer tissue correlated with clinical stage. Expression of these factors in the ovarian cancer tissues with patient age, pathological type, lymph node metastasis has not correlated.Conclusions:1. Apoptosis regulatory factors XIAP、Survivin、Caspase-3and transcrip-tion factor AP-1(c-Jun、NF-KBp65、IκB-a in ovarian normal tissue, benign ovarian tumor, borderline ovarian tumors, ovarian cancer rate and expression intensity was gradually increased,These result suggest that these inhibitory factory factor and regulatory factors may be involved in the occurrence and development of ovarian tumors, and can be used as a diagnostic and differential diagnosis of ovarian tumors of reference.2. Expression of XIAP、Survivin and Caspase-3 increased according to the cinical stage of ovarian cancer, suggesting that these factors may be involved in the differentiation of ovarian cancer and ovarian response to some extent Cancer malignancy And indicates a poor prognosis.3. Expression of XIAP、Survivin correlate to the expression of NF-KBp65 suggest that NF-KBp65 has a facilitating role on the expression of XIAP、Survivin.4. Expression of transcription factor AP-1 (c-Jun) and the transcription factor NF-KBp65 in ovarian cancer tissues were positively correlated, suggesting that these factors may play a promoting role on the development of ovarian cancer.5.Expression of apoptosis regulatory factors XIAP、Survivin、Caspase-3 and transcription factors AP-1 (c-Jun)、NF-KBp65、IκB-αwith age、pathological type、lymph node metastasis and other factors had no relationship.