Gene Marker May Identify Risk for Recurrence of Endometrial Cancer

Contact:
Darrell E. Ward
(314) 286-0122
wardd@msnotes.wustl.edu

May 29, 2002 – Researchers at Washington University School of Medicine in St. Louis have found a possible marker for women at risk for recurrent endometrial cancer, a disease that is usually fatal. The study also suggests that African-American women may be at higher risk for recurrence of this malignancy. The findings are published in the June 1 issue of the journal Cancer.

"This exciting preliminary finding may improve the management of women with endometrial cancer and may provide insight into the biology of endometrial tumors," says Matthew A. Powell, M.D., instructor of obstetrics and gynecology and lead author of the paper.

The American Cancer Society predicts that 39,300 women in the United States will develop endometrial cancer this year and that 6,600 of them will die of the disease. Caught early, 96 percent of women treated are disease-free after five years, but that rate drops to 63 percent if the disease has spread to nearby lymph nodes and to 26 percent if it has spread to other areas of the body.

Doctors have clear guidelines for treating women diagnosed early, with tumors confined to the endometrium, the inner lining of the uterus: The uterus is surgically removed, and the women are likely to be cured of the disease. Women diagnosed with advanced disease -- tumors that have spread to the lymph nodes -- must be treated aggressively with surgery followed by radiation and perhaps chemotherapy.

But physicians are often unsure about how to treat women with intermediate-stage tumors - those that have invaded the underlying muscle of the uterus but have not spread to the lymph nodes - the stage at which most women with endometrial cancer are diagnosed.

In five or six percent of these women, tumor cells already have spread at the time of surgery and those undetectable cells become the source of recurrent tumors. Because doctors can't identify which women with intermediate disease will experience a recurrence, many of these patients are treated with radiation as a precaution.

"We hope this marker will help us identify women who are unlikely to have a recurrence and thereby help us avoid giving radiation to patients who don't need it," says Paul J. Goodfellow, Ph.D., professor of surgery and of obstetrics and gynecology, associate professor of genetics and principal investigator for the study. 

The research team also included David G. Mutch, M.D., the Ira C. and Judy Gall Professor in Obstetrics and Gynecology, Janet S. Rader, M.D., associate professor of obstetrics and gynecology, and Thomas J. Herzog, M.D., associate professor of obstetrics and gynecology.

The study investigates the prognostic significance of a chemical change in DNA known as methylation. Healthy cells use methylation to turn off unused genes; tumor cells often have abnormally elevated levels of methylation.

In this study, researchers for the first time looked at methylation of ribosomal DNA (rDNA) in endometrial tumor cells. Instead of carrying instructions for making a protein, rDNA carries instructions for making ribosomes -- tiny structures in cells that help link amino acids together to make proteins.

The study involved 215 women with endometrial cancer. Of these, 176 were Caucasian and 39 were African American. The median age of surgery was 66 years (range 30-93 years). The researchers correlated the presence of methylation with the outcome of the women following treatment. More than two-thirds of the women (69 percent) had intermediate-stage tumors.

The researchers found that rDNA from healthy cells from the women showed little rDNA methylation, while 74 percent of tumor cells showed high levels of rDNA methylation.

"Then came the surprise," says Goodfellow, who also leads the Cancer Genetics Program at the School of Medicine and Barnes-Jewish Hospital's Alvin J. Siteman Cancer Center. "Tumors that showed low levels of methylation were much more aggressive and more likely to recur. Furthermore, African-American women were more likely to have tumors showing low levels of rDNA methylation." Of the African-American patients, 46 percent showed low levels of rDNA methylation compared to 22 percent of Caucasian patients.

These results, which must be verified by studies in larger groups of women, suggest that testing endometrial cancer cells for rDNA methylation may help identify patients with intermediate-stage endometrial cancer who are likely to have a recurrence and should receive radiation therapy following surgery, while sparing others from unnecessary treatment, says Goodman.

The researchers now are preparing to study an additional group of patients and are developing a clinical test to detect rDNA methylation.

Endometrial cancer usually occurs in postmenopausal women. The most common sign is vaginal bleeding or spotting. "Any woman who experiences abnormal vaginal bleeding should be examined by a physician," says Powell.

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Powell MA, Mutch DG, Rader JS, Herzog TJ, Huang TH-M, Goodfellow PJ. rDNA methylation in endometrial cancer: an independent prognostic marker. Cancer, 94 (11), 2941-2952, June 1, 2002.

This research was funded by grants from the National Cancer Institute.

The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
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