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Protein Announces Presence of Ovarian Cancer

New marker could improve early detection efforts

FRIDAY, Oct. 5, 2001 (HealthDayNews) -- A protein footprint left in the blood by ovarian cancer cells could offer doctors a way to detect the disease early enough to treat it effectively, suggests a new study.

The study shows that secretion of prostasin, an enzyme also found in the prostate gland and several other body tissues, is significantly elevated in ovarian cancer cell samples. Researchers say the enzyme appears to be equally prevalent in both mature and early-stage ovary tumors, suggesting that it could be pressed into service as a cancer-screening tool, especially in tandem with other genetic markers of malignancy. A report on the discovery appears in the latest issue of the Journal of the National Cancer Institute.

An estimated 27,000 women in the United States will be diagnosed with ovarian cancer this year, and 14,000 will die from the disease, the American Cancer Society says. Surgery and drug therapy are effective treatments against the disease, but since the overwhelming majority of tumors are detected late, the prognosis for most patients is poor.

Treating ovarian cancer before it advances enough to spread or cause symptoms is imperative. Since the organs are well hidden in the body, signs of abnormal growth aren't readily apparent and biopsies are difficult.

But one way to get the jump on tumors -- an approach that has become a major focus of recent cancer research -- is to look for telltale chemical traces of their activity.

The most accurate ovarian cancer marker yet discovered is a blood-borne protein known as cancer antigen 125 (CA 125), which is secreted by these tumors. Testing for CA 125 levels is common in women with suspicious ovarian lesions. The antigen also may prove to be a useful target for an annual test for ovarian cancer.

In the latest study, a team led by Dr. Samuel Mok of Brigham and Women's Hospital in Boston used DNA chip technology to screen for other genetic markers of ovarian cancer in 64 women with the disease and 137 without it.

Blood levels of prostasin were about twice as high in samples of malignant cells from ovarian cancer patients as they were in tissue from healthy women. Mok's group also found that prostasin levels dropped in 14 of 16 women who had surgery to remove the cancer.

Prostasin belongs to a group of enzymes called serine proteases, whose job it is to chew up other proteins. Why it's hyperactive in ovarian cancer cells isn't certain, but that activity may have something to do with allowing those cells to spread, Mok says.

Mok says testing for prostasin is easy. And while screening for CA 125 is both more sensitive, more specific and less likely to miss tumors, it has limitations. However, combining the two tests could enhance detection possibilities into the 90 percent range, the researchers say.

The study showed that prostasin appeared to be an effective marker only for ovarian cancers known as serous cell tumors, which make up about 60 percent of all cases. Additional work is needed to see if the protein also is over-expressed by the three other forms of ovarian cancer, says Mok. He says his team plans to study the marker in a larger group of patients.

Dr. Eddie Reed, director of the Mary Babb Randolph Cancer Center at West Virginia University in Morgantown, says CA 125 is "extremely useful" for helping doctors determine the effectiveness of ovarian cancer therapy and whether the disease is in remission.

But the marker is less adept as a screening device. "The first limitation is it is unclear how early in the process the CA 125 will be elevated," says Reed, an ovarian cancer specialist and former National Cancer Institute researcher. In addition, pregnancy and nursing, as well as non-cancerous diseases like endometriosis and even cirrhosis of the liver, boost CA 125 levels in women. That dilutes the significance of a spike in the marker, he says. "It's not good enough to be used by itself."

What To Do

For more about screening methods, check the Early Detection Research Network, an initiative coordinated by the National Institutes of Health.

To find out more about CA 125, try the University of Pennsylvania.

For more about ovarian cancer, try the National Ovarian Cancer Coalition.

SOURCES: Interviews with Samuel Mok, Ph.D., director, laboratory of gynecologic oncology, Brigham and Women's Hospital, Boston, and Eddie Reed, M.D., director, Mary Babb Randolph Cancer Center, West Virginia University, Morgantown; Oct. 3, 2001, Journal of the National Cancer Institute
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