Ovarian Cancer

Ovarian cancer is the second most common gynecological cancer among women. Because the tumor is not detected until late in its development, usually not until after it has spread beyond the ovary, it is difficult to treat. Thus, ovarian tumors are often fatal and account worldwide for almost half of the deaths from cancer in the female reproductive tract. Tumors of the ovary are classified by the cell type of origin—surface epithelium, germ cells, and stromal tissue. Metastatic ovarian cancer is also common. Most (around 90 percent) ovarian tumors arise from the ovarian surface epithelium (OSE) and produce relatively mild symptoms until the disease is far advanced. Symptoms include abdominal pain and distention, urinary and gastrointestinal tract symptoms resulting from compression by the tumor or invasion into adjacent organs, and vaginal bleeding. At late stages, tumors cause progressive weakness and unintended weight loss. Carcinomas extending beyond the ovary tend to seed the peritoneal cavity, covering the serosal surface diffusely with small (0.1–0.5 cm) surface implants and causing massive fluid accumulation (ascites). The five-year survival rates are poor (30 to 40 percent), thus, prevention and early detection are of high priority.

Family history of ovarian cancer is a major risk factor in 5 to 10 percent of cases. Risk increases from 1.4 percent in the general population to 8 percent in women with two affected first-degree relatives. Strong associations with familial breast cancer, and a lesser association with familial colon and endometrial cancer are known. Biomarkers for early detection include CA-125, a high molecular weight glycoprotein present on more than 80 percent of epithelial ovarian tumors, and osteopontin, expressed at high levels in ovarian cancer patients. Proteomic assays that examine the patterns of circulating proteins in patients compared with nonaffected controls are being conducted, but require validation before they can be used as screening modalities. Current screening strategies for at-risk women, assessed by positive family history, include testing for mutations in germ line tumor suppressor genes such as BRCA1 and BRCA2. Prophylactic removal of the ovaries is current practice for women at high risk, but the impact of these strategies on ovarian cancer death rate has not been determined.

The processes leading to ovarian tumor development are similar to processes for cancer initiation, promotion, and progression described in the “Obesity and Cancer” entry in this encyclopedia. The stationary ovarian surface epithelium (OSE) is a flat to cuboidal layer of epithelial cells with few distinguishing attributes. While on the ovarian surface, the OSE transports materials to and from the peritoneal cavity and takes part in cyclical follicle rupture and ovarian surface repair. Sometimes, in the process of follicle rupture, epithelial cells become entrapped in the underlying stroma. Through the years, after many cycles of rupture and repair, epithelial cells can become incorporated into the stroma. Normally, trapped epithelial cells differentiate and become incorporated into the ovarian stroma as stromal fibroblasts. Some epithelial [Page 569]cells are unable to differentiate into fibroblasts, retain their epithelial phenotypes and aggregate within the stroma as inclusion cysts. While on the ovarian surface, epithelial cells do not express membrane-bound markers; however, epithelial cells in inclusion cysts are known to express a variety of markers including CA-125. It is these trapped epithelial cells that have a high potential to transform into cancer cells.

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