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High levels of Bcl-2 in urine may flag ovarian cancer.

SAN DIEGO -- High levels of Bcl-2--an anti-apoptotic protein that promotes cell survival--in urine could be a marker for ovarian cancer, according to a study of data from urine samples from 295 women.

The average amount of Bcl-2 in the urine of patients with ovarian cancer was up to 10 times greater than for healthy controls in the study reported by Dr. Patricia Kruk, of the University of South Florida, Tampa, in a poster at the annual meeting of the American Association for Cancer Research.

"Measuring urinary Bcl-2 could provide a safe, specific, and economical way to detect ovarian cancer at an early, and therefore potentially curable, stage," Dr. Kruk and her coauthors suggested.

The symptoms of ovarian cancer--gas, pelvic pain, abdominal bloating--are nonspecific and experienced by virtually all women from time to time. Because these signs are so vague, most women with ovarian cancer are diagnosed with late-stage disease and have a very poor prognosis, with 5-year survival no better than 37%. Dr. Kruk said, "Many people refer to this as the disease that whispers because there are no symptoms."

To validate an earlier pilot study that found high urinary levels of Bcl-2 were associated with ovarian cancer, she obtained additional urine samples from Dr. Robert Bast of the University of Texas M.D. Anderson Cancer Center, Houston. The samples were collected from 58 normal, healthy volunteers, 122 patients with benign gynecologic disease, and 115 patients with ovarian cancer. They were measured for Bcl-2 by enzyme-linked immunosorbent assay (ELISA).

The average amount of Bcl-2 in the urine of ovarian cancer patients was greater than 2 ng/mL and up to 10 times greater than in healthy controls or in patients with benign disease. With logistic regression, the investigators calculated that the predicted odds of cancer increased 27% with a 0.1-ng/mL increase in urinary Bcl-2 (P less than .001). Analysis of variance (ANOVA) analyses of clinical parameters indicated that the urinary levels of Bcl-2 were not significantly related to tumor size, grade, or stage.

Urinary Bcl-2 was more accurate in identifying ovarian cancer than was cancer antigen 125 (CA125), which is currently considered the accepted standard for ovarian cancer detection, Dr. Kruk said.

"The CA125 test is the best test we have, but it's not 100% accurate. Some people say it ranges anywhere from 50% to 70% in accuracy and specificity, so there are a number of false positives and false negatives," she said. "We found that our urinary Bcl-2 test performs at least as well, and in some instances better than the C125 test."

Dr. Kruk also reported that urinary levels of Bcl-2 decreased in ovarian cancer patients following initial debulking surgery and remained low while the women were receiving chemotherapy. However, these levels increased significantly with recurrence of disease.

The urine test has been patented and has been licensed to GeoPharma Inc., she added.

"The hope is that this test will be used as part of a woman's annual physical examination, right in her doctor's office. A urine test is very simple, we would expect high patient compliance, and used either alone or in conjunction with C125, might be a better way to diagnose ovarian cancer," she said.

Diagnosing ovarian cancer at an earlier stage will save lives, Dr. Kruk said.


Orlando Bureau
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Author:Lowry, Fran
Publication:OB GYN News
Date:May 1, 2008
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