Dissertation > Medicine, health > Oncology > Genitourinary tumors > Female genital tumors > Ovarian tumors

Expression and Clinical Significance of WT-1,ER,PR in Ovarian Serous Cancer

Author ChenDong
Tutor WangGuoPing
School Huazhong University of Science and Technology
Course Pathology
Keywords WT-1 ER estrogen receptor PR progesterone receptor ovarian serouscarcinoma
CLC R737.31
Type Master's thesis
Year 2012
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Background and objectiveRecent years, more and more researchers come to study about Wilm’s tumor gene(WT-1gene) and they found in addition to the embryonic kidney, spleen and leukemia,WT-1gene can also express in epithelia ovarian tumors. Some researchers believedthat WT-1can be used as a sensitive indicator to identify some epithelial ovariantumors. The major physiological function of WT-1protein is to recognize and bind tospecific target DNA and thus plays the role as the transcription regulator. The specificmechanism of WT-1gene abnormal expression in ovarian tumors is still unclear, whichneeds further study. It may be associated with the gene mutation, DNA methylationand histone deacetylation. With the extensive developing of research, people haveachieved some successes in the WT-1antisense gene therapy and the WT-1genevaccine which provide new ideas and new perspectives for the treatment of tumorimmunity.The ovaries are the important endocrine target organs of females and there are verysophisticated synergistic or antagonistic effects among various hormones in them.Studies have shown that the ovarian cancer morbidity rate of postmenopausal women was significantly higher than those who are at reproductive age, and the mostsignificant endocrine changes of postmenopausal women lay in the gonadal hormonelevels. In contrast, those who have a long-term use of oral contraceptives or withmultiple pregnancies are at a low level of women gonadotropin in vivo. During thepast20years, molecular biology researches of the female sex hormones regulationgene expression have further deepened the understanding of the close relationshipbetween the endocrine and ovarian tumor. It has become a consensus that endocrinefactors are the most important risk factor in the pathogenesis of ovarian cancer. As theimportant sex hormones in the body of the females, estrogen and progesterone play abiological role through their respective receptors. Although its mechanism of actionand impact in the development process of epithelial ovarian tumors is not clear,endocrine therapy remains providing a new direction and ideas in the treatment ofovarian tumors.Ovarian serous carcinoma (OSC) is the most common histologic type of epithelialovarian cancer which is characterized as rapid progression, prone to metastasis, higherrecurrence and mortality rate. There are no effective methods for early diagnosis as sofar. Only CA125in serum and vagina B-ultrasonography become the most valuableexamine methods, but both of them are lack of specificity and sensitivity and of littlesignificance in the tumor screening.60%to70%of patients come to visit doctor withthe OSC lesions beyond the pelvic range. OSC has become a serious threat to women’shealth in malignant cancer characterized as low5-year survival rate, hovering in therange of25%to30%. In this paper, the WT-1, ER and PR expression levels wereexamined by immunohistochemistry in55cases of ovarian serous carcinoma, used toexplore the relationships between their expressions and clinicopathologic factors (suchas age, tumor size, differentiation degree, stage, lymph node metastasis, ascites), aswell as the relationships among their three, aiming to provide a theoretical basis for theclinical diagnosis of ovarian serous carcinoma and endocrine therapy. Method1.55cases of ovarian serous carcinoma were collected from the pathology departmentof Tongji hospital, Huazhong University of Science and Technology, all of which weresurgical resected during August2008to May2012and pathologically diagnosed asovarian serous carcinoma as their final results. Patients, aged between32-74years old,were all newly diagnosed and none of them received preoperative radiotherapy orchemotherapy before surgery. Their clinical medical records were of great integrity.2. The tumor tissues were made into pathologic slices. The expression of WT-1, ERand PR protein were observed under the microscope, stained byimmunohistochemistry.3. The data were analyzed by Chi-squared test, Fisher’s exact test and Spearman rankcorrelation by the means of SPSS19.0software and thus explored the relationshipsbetween the expressions and clinicopathologic factors (such as age, tumor size,differentiation degree, stage, lymph node metastasis, ascites), as well as therelationship among the three above.Results:1. WT-1expression had no significant difference among the clinicopathologic factorsgroups (P>0.05).2. ER expression had no significant difference among the clinicopathologic factorsgroups (P>0.05).3. The PR expression had no significant difference among the clinicopathologic factorsgroups (P>0.05), except the group of ascites (P<0.01).4. The expression levels of WT-1showed correlation with ER(P<0.05), but thereappeared no statistically significant difference between the expression levels of WT-1and PR, the same as ER and PR(P>0.05). Conclusions1. WT-1protein, ER and PR protein were all showed expressions in OSC. The rates oftheir expressions were96.4%,74.6%and29.1%respectively. The expression of WT-1protein could be used as a new target to provide a theoretical basis for OSC genetargeted therapy. The expressions of ER, PR could be used to determine the tumor’ssensitivity to hormones and will contribute to endocrine therapy to some degree.2. The expression levels of WT-1and ER showed no significant correlation with theOSC clinicopathological indicators (age, tumor size, stage, histology, lymph nodemetastasis and ascites), therefore either of them could be used as a basis to determinethe biological behavior of OSC tumor.3. It has been reported that ascites was associated with prognosis of ovarian cancer,and this study showed that the level of PR expression had significant correlation withascites (P<0.01).Therefore ascites could be combined together with the expression ofPR as prognostic indicators of the OSC to some extent.4. The expression level of WT-1was associated with ER, which suggested the twoabove both acted in the OSC occurrence progression. If the mechanism could beelucidated, it may aid in providing new ideas and methods of clinical diagnosis andtreatment for the OSC.

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