PNDRI | June 25, 2003: New Ovarian Cancer Hope For Women

Frequently Asked Questions

Here are some of the more likely questions about ovarian cancer diagnosis and the July 1, 2003, Cancer Research paper concerning HE4. For more detailed background information, contact Rich Murphy, Director of Community Relations at PNRI (now PNDRI), 206-726-1200, rmurphy@pndri.org.

What is ovarian cancer?

Ovarian cancer is cancer that begins in the cells that constitute the ovaries, including surface epithelial cells, germ cells, and stromal cells. Cancer cells that spread from other organ sites to the ovary (most commonly breast or colon cancers) are not considered ovarian cancer.

The most common type of ovarian cancer is epithelial.

(source: National Ovarian Cancer Coalition)

What is the incidence of ovarian cancer?

The American Cancer Society estimates that more than 25,000 new cases of ovarian cancer will be diagnosed in the U.S. in 2003. More than 14,000 deaths are expected to occur from the disease this year. Ovarian cancer causes more deaths than any other cancer of the female reproductive system.

If the disease is diagnosed and treated in its early stages, it can often be effectively managed. 95% of patients with early diagnosis survive at least five years after treatment. But only 25% of all cases are detected early.

(source: American Cancer Society, Cancer Facts and Figures (555KB PDF))

What does the Hellstrom study in Cancer Research show?

Researchers demonstrate that ovarian cancer can be detected in a new and more reliable way. They show that a protein very common to ovarian cancer cells, but very rare in other cells-HE4-can be used to recognize the presence of ovarian tumor cells. This finding suggests that a new and improved clinical test for ovarian cancer may be possible and earlier diagnosis of the disease may be within reach.

How many patients were tested in the Hellstrom study?

Blood samples from 121 women were tested in blind assays. 37 had ovarian cancer; 19 had benign ovarian disease; 65 were healthy. With perfect specificity-i.e., with no false positive results-the Hellstrom test for ovarian cancer was 40% more exact than the only other biomarker test available.

What special test did the study use to detect HE4?

Technically, a double determinant ELISA.

The researchers created two antibodies to different components of the HE4 molecule. Both antibodies bind themselves to the protein only when it is HE4, and the presence of HE4 is highly correlated with the presence of ovarian carcinoma.

Who were the scientists collaborating with Dr. Hellstrom in the HE4 study?

John Raycraft, Martha Hayden-Ledbetter, Jeffrey A. Ledbetter, and Karl Erik Hellstrom, at PNRI. Michel Schummer, at Institute for Systems Biology. Martin McIntosh, Charles Drescher, and Nicole Urban, at the Fred Hutchinson Cancer Research Center. The Marsha Rivkin Center for Ovarian Cancer Research also supported the work.

Why is ovarian cancer so hard to detect?

The ovaries are located so deep in the pelvis that they cannot be seen directly without surgery. Small ovarian tumors are difficult for even the most skilled examiner to feel. Early cancers of the ovaries tend to cause no symptoms or symptoms that are relatively nonspecific. By the time symptoms appear or ovarian cancer is considered as a possible cause, the cancer may have already spread beyond the ovaries.

Women may be screened for ovarian cancer by ultrasound and blood tests. However, even when an ultrasound finds a mass in the ovary, it does not accurately predict which masses are cancers and which are due to benign disease. Blood tests for measuring the amount of CA125 (cancer-associated antigen 125) in the blood are also inexact. Some noncancerous diseases of the ovaries can also increase the blood levels of CA125 and some ovarian cancers may not produce enough CA125 to cause a positive test.

(source: American Cancer Society)

What are the stages of ovarian cancer?

Untreated ovarian cancer moves through four general stages. In the first, cancer cells grow within and on the surface of the ovaries. In the second, the tumor remains within the pelvis, but it extends to the uterus, fallopian tubes, and other pelvic organs. In both the first and second stages, the tumor is said to be "primary."

In the third stage, ovarian cancer spreads beyond the pelvis to the lining of the abdomen and then to the lymph nodes. In the fourth stage, the most advanced, the cancer spreads to organs beyond the abdomen. Ovarian cancer in the third and fourth stages is said to be "metastatic."

What is CA125?

CA125 is a protein produced by a variety of cells, including some ovarian cancer cells. Levels of CA125 in the blood may go up in women with ovarian cancer. High levels of CA125 can also occur when other cancers are present, and sometimes when benign conditions are present. The CA125 blood test is approved by the FDA to monitor patients with ovarian cancer, but is considered experimental as a screening test.

(source: National Cancer Institute)

What is HE4?

HE4 is a protein that is over-expressed in ovarian cancer, but its expression in normal tissues is low. Because HE4 is secreted from cancer cells into the blood, it is possible to test for the presence of this protein in small quantities of serum in the laboratory.

HE4 was discovered in 1991, but was not associated with ovarian cancer at that time. Its function is still unknown. But the study by Hellstrom and her colleagues demonstrates that it is possible to use HE4 as a new biomarker for ovarian cancer. In early results, it promises to be at least as specific as CA125 and significantly more sensitive.

How do CA125 and HE4 compare as biomarkers for ovarian cancer?

CA125 is the only commercially available clinical biomarker for diagnosing ovarian cancer. But CA125 does not detect all instances of ovarian cancer in patients, and sometimes it indicates the presence of cancer in patients who are in fact tumor free.

The HE4 assay, on the other hand, detected a similar percentage of actual cancer cases as CA125, but it indicated significantly fewer "false positive" results.

Is HE4 being developed for clinical use?

Yes. Fujirebio Diagnostics, in a license agreement with Hellstrom and PNRI, is confirming the laboratory assay results and working to develop a new clinical diagnostic test. The most promising possibility is that a new, combined test may be developed. When CA125 and HE4 are both used to test serum samples, the specificity and sensitivity of their combined diagnosis is significantly greater than either alone.

How soon will a test be available for clinical use?

Scientists are still years away from a commercially available test for widespread use in clinical settings. In the meantime, laboratory research continues in the search for other complementary ovarian cancer biomarkers. Commercial development of multiplex tests is underway. Clinical trials will be undertaken.

In the meantime, HE4 is the most promising ovarian cancer biomarker discovered to date, and it should give patients and doctors hope that effective ovarian cancer diagnosis is on its way.