On the Trail of a Killer : Blood Test Developed at UCI May Detect Ovarian Cancer Earlier
A new blood test for ovarian cancer developed at UC Irvine has become the focus of a national study to determine if eventually it could speed detection of the disease, which often kills its victims by growing undiscovered.
With the approval of the National Cancer Institute, 140 women with ovarian cancer will be followed from their original diagnosis through two years of treatment, including surgery and chemotherapy, to see if the test can accurately detect changing levels of malignancy.
Dr. Gale Granger, a UCI microbiologist who pioneered the basic research behind the new test, said that when it was tried on stored blood from 53 ovarian cancer patients, it proved much more sensitive than the standard blood test now used to monitor ovarian cancer.
If the study shows the test can detect changes in malignancy in women known to have cancer, it is hoped it eventually could be used as a screening test for early detection of ovarian cancer. No such test exists now.
Granger cautioned, however, that although the new test shows promise, this larger study of current patients--not one that uses stored blood--is needed to confirm the preliminary results.
The nationwide study is being jointly conducted by UCI and Long Beach Memorial Medical Center. The Gynecologic Oncology Group, a national research coalition of major medical centers funded by the National Cancer Institute, will provide the cancer patients and their blood samples.
Gynecologists have long been waiting for a diagnostic test for ovarian cancer that would be comparable to a Pap smear for cervical cancer, said Dr. Philip J. DiSaia, director of gynecology oncology at UCI, whose department has collaborated with Granger’s researchers in developing the new assay.
DiSaia said the standard test for ovarian cancer, which looks for an antigen produced by cancer cells called CA 125 in the bloodstream, has many shortcomings and is not sensitive enough to be used as a screening device. The test works by detecting the level of CA 125; a higher level means more malignancy.
“If a woman has a tumor the size of a hen’s egg, there is only a 50% chance of having a positive CA 125 test,” he said. Moreover, he added, more than half of the time when the CA 125 level drops to zero during therapy, exploratory surgery will still find active cancer.
The new test works by detecting the level of a protein molecule emitted by cancer cells.
Yet another problem with CA 125 is that it occurs in low levels when women have medical problems not related to cancer, such as endometriosis and uterine fibroids.
Dr. Otis Browley, program director in the National Cancer Institute’s division of cancer prevention and control, agreed that a more accurate test for ovarian cancer would be welcome.
“If it has high sensitivity for cancer still in the ovary, it would be wonderful,” he said, noting that ovarian cancer diagnosed at this stage can be cured more often than when it has spread to other body organs.
Women whose cancers are detected in the earliest stage--while confined to the ovaries--have an 88% chance of surviving five years after their diagnosis, according to the American Cancer Society.
But ovarian cancer, which will kill about 13,600 American women in 1994, usually shows no obvious symptoms until late in its development; only 23% of ovarian cancers are discovered early. Most often by the time the cancer is discovered, it has spread beyond the ovaries, when the chance of survival for five years after diagnosis plunges as low as 17%.
UCI officials say the new ovarian cancer test was developed after basic researchers at UCI teamed with gynecologists working at UCI and Long Beach Memorial Medical Center. For 20 years Granger’s research group at UCI has studied protein molecules called tumor necrosis factors, which the body’s immune system produces to kill cancers.
Until five years ago, researchers were puzzled why these weapons didn’t do their job very well. At that time, UCI scientists discovered that cancerous tumors secrete blocking agents that intercept and, in effect, defuse cancer-killing TNF. These blocking agents mimic the receptors on the cancer cells that the TNF uses as an entryway to the malignant cells. As a result, many of the TNF cells spend themselves attacking false targets. The researchers isolated these agents and developed a laboratory test to detect them in body fluid.
But it was a gynecologist fellow at UCI, who was working with the basic researchers, who had the idea that the microscopic blocking agents found in the fluid surrounding ovarian cancers could be used as a marker for ovarian cancer.
“I thought if we can pick it up in the fluid, maybe we can pick it up in the blood.” said Dr. Elizabeth A. Grosen, who now is completing her specialty education at the City of Hope.
To test her hypothesis, Grosen applied the new test to blood belonging to ovarian cancer patients whom DiSaia had treated over the years at UCI Medical Center and Long Beach Memorial Medical Center.
She found that the TNF blockers, called soluble TNF receptors, were elevated in the blood of women with diagnosed cancer and declined as cancer therapy progressed, mirroring the decline of CA 125. An article on the research was published last year in Gynecologic Oncology.
Most important, the TNF blockers continued to be detectable through blood testing after CA 125 had disappeared from the blood of patients who still had cancer even of microscopic size. These malignancies were found through biopsy or surgery.
“Based on the results of the testing they have done at UCI, it looks promising,” said Dr. Edward Trimble, who gave the National Cancer Institute’s approval to the expanded study. He said other medical centers also are looking for markers such as antigens produced by cancer tumors that in combination with CA 125 might be more effective in detecting ovarian cancer.
The blood samples collected by the Gynecologic Oncology Group will be tested at Memorial Cancer Institute of Long Beach Memorial Medical Center. The test results then will be sent to the Gynecologic Oncology Group office in Philadelphia where they will be statistically analyzed.
The gathering of blood samples for the new study began in March, Granger said. He emphasized that if the study determines that TNF blockers are a better measurement of cancer than CA 125, a much larger future study will be needed to learn if this new test is accurate enough to be used as part of a routine examination to screen women for the first signs of ovarian cancer.
Granger said there is also some evidence that TNF blockers may indicate the presence of other kinds of cancer. “It is kind of opening a door,” he said of the research under way.
The Body’s Battlefield
How the body tries to fight ovarian cancer and how cancer fights back.
How cancer defends itself: When white blood cells releases TNF, cancer cells responds by releasing countless imposters. TNF is neutralized if it latches on to an imposter. Receptor: Vulnerable spot of cancer cell where TNF can attach. Imposter: Phony receptors released by cancer cell to fool TNF. TNF: Powerful, tumor-fighting protein released by white blood cell. White blood cell: Fights infections. How white cell fights cancer: White blood cell releases TNF; it searches; for the real receptor. If TNF finds real receptor, it connects like a jigsaw puzzle piece and begins killing the cancer cell.
Source: Dr. Gale Granger; Researched by CAROLINE LEMKE / Los Angeles Times
