A new test designed to detect hidden ovarian cancer in patients finishing treatment for the disease appears more sensitive than a standard assay, USC/Norris scientists found in an initial comparison of the two methods. They reported the findings in the Feb. 4 Journal of the National Cancer Institute.
The study marks the first step in the development of a test that may be used to determine who has been successfully treated with chemotherapy and who still harbors remnants of disease, said Louis Dubeau, a USC/Norris pathologist who co-authored the study with Bridgette Duggan, a gynecologic oncology fellow at the Norris.
“Physicians are in dire need of a better test,” Dubeau said.
Ovarian cancer is much less common than other gynecological cancers, yet it remains very deadly, proving fatal for some 13,000 women each year. Many women successfully battle the tumor initially, only to have the disease return. Part of the problem is the lack of a sensitive test that will pick up the few rogue tumor cells that may remain after therapy.
To catch such cancer cells, doctors now use a “second-look surgery,” in which surgeons take biopsies and wash fluids through the abdomen to look for signs of cancer. Though this procedure is considered the most sensitive available, it often fails to find residual disease. Nearly half of patients who show no sign of disease with the second look go on to develop subsequent tumors.
In a 1997 paper, Dubeau and his colleagues suggested another way. They found ovarian cancer cells have unusually high levels of telomerase. Telomerase is an enzyme critical to cell replication – without it, cells can only divide a set number of times before damaging the chromosomes. Usually, adult cells in the body don’t need telomerase since they have a limited life span. But most cancer cells, with a potential to grow and divide endlessly, produce lots of telomerase.
Since then, Dubeau has labored to find out whether telomerase can be used as a marker of the disease in patients. The recent study compared the ability of an assay for telomerase with a cytological exam to detect cancer.
In this study, Dubeau’s team ran both tests on 42 women with active ovarian cancer (determined by biopsy) and 43 controls – women with either benign ovarian cysts or liver failure, but not cancer. In the study, half the washing fluid from each patient was sent to cytologists, and the other half was analyzed by Dubeau’s team. They found that the telomeric assay was more sensitive – 88 percent of the cancer patients tested positive with the telomerase assay compared to 64 percent with the cytological exam. The telomerase assay identified as positive 10 cases that cytological analysis missed. In related test tube experiments, Dubeau showed that the assay could detect as few as 10 to 50 cancer cells in a sample.
The telomerase assay proved to be highly specific- only two control patients who did not have cancer showed “false positive” results. Five patients’ tumors weren’t detected by either test, highlighting the need for further study and development of the test. “We need to understand in what patients this test will work best in,” Dubeau said.
“There’s a lot of promise in using telomerase as a marker of disease,” Dubeau said. “Along with colleagues at many study centers around the country, we’re now following up on this study to see if the new test will reliably predict recurrence.”
Duggan, B.D., Wan, M., Yu, M.C., Roman, L.D., Muderspach, L.I., Delgadillo, E., Li W.-Z., Martin, S.E. and Dubeau, L. “Detection of Ovarian Cancer Cells: Comparison of a Telomerase Assay and Cytologic Examination.” JNCI, vol. 90, no. 3, p238-242