CA125 Expression on Spontaneous Ovarian Adenocarinornas from Geriatric Laying Hens

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Title: CA125 Expression on Spontaneous Ovarian Adenocarinornas from Geriatric Laying Hens
Author: Jackson, Emily Dawn
Advisors: Kenneth E. Anderson, Committee Member
Chris M. Ashwell, Committee Co-Chair
Paul E. Mozdziak, Committee Chair
Abstract: Despite years of research ovarian cancer remains the most lethal of all gynecological malignancies. Ovarian cancer is the fourth leading cause of cancer death among women in the United States. It is estimated that in the United States in 2007 there will be 22,430 new cases of ovarian cancer diagnosed and 15,280 deaths. The high mortality rate is due to the fact that ovarian cancer typically presents itself as a late stage disease. There is currently no method to detect ovarian cancer in the early stages when the disease is 90% treatable. Progress toward understanding the ovarian cancer disease process is hindered by the absence of a biologically adequate animal model. Domestic hens maintained under intensive egglaying conditions spontaneously develop ovarian adenocarcinomas. A typical hen will produce 280 or more eggs in 50 weeks. Just as in older females, fertility in hens decreases after 2 years of age. The first objective in the current study was to further establish the chicken as an acceptable animal model for human disease. This was done by determining the presence of a known ovarian cancer tumor marker, CA125, in avian ovarian cancer tissue samples and cells isolated from solid tumors. CA125 is a glycoprotein expressed on the cell surface of ovarian cancer cells and has a molecular weight above 200 kDa. In the avian species CA125 is represented by a band of molecular weight 25-50 kDa. The objective of the second experiment was to determine if stage or level of metastasis has an affect on CA125 expression in avian ovarian cancer samples. CA125 has been established as a tool in the clinical setting for following progression of disease and response to treatment because CA125 increases with recurrence of disease after remission. The level of metastasis is significant because ovarian cancer typically is not detected until late disease stage when tumors have spread beyond the ovary to other body organs. Increased levels of CA125 would therefore be correlated with increased levels of disease spread throughout the body cavity. Despite the evidence seen in human clinical results, this experiment did not show any correlation between CA125 expression and disease stage or level of metastasis. The third objective was to evaluate the presence of CA125 in oviductal tumors. CA125 production may play a significant role in determining the primary site of tumor formation, which aids in disease management. This experiment tested whether avian primary oviductal tumors express CA125. It also tested whether oviductal tumors secondary to ovarian cancer expressed CA125. It has been shown that CA125 can be shed from a primary tumor and attach to mesothelin on the mesothelium in the peritoneal cavity to allow metastasis to occur. The results suggest that primary oviductal tumors do not express CA125 and secondary oviductal tumors also do not express CA125. The objective of the fourth experiment was to compare CA125 expressed in human ovarian cancer with samples taken from avian ovarian tumors. Objective 1 resulted in a protein of ˜50 kDa while the reported CA125 protein detected in humans is 200 kDa. The second aim in the current study was to determine if there is a correlation between E-cadherin and the tumor marker, CA125. There is controversy about the status of E-cadherin expression in human ovarian disease. Finding a link between the cell adhesion molecule and CA125 may shed light onto the role of CA125 in ovarian cancer. We found that CA125 is expressed in a human ovarian tumor, while there was no E-cadherin expression in any avian sample.
Date: 2007-12-21
Degree: MS
Discipline: Physiology

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