DNA test may help with endometrial cancer screening

Volume 4, Issue 3, 2015


Researchers have shown that endometrial cancer can be detected from tumor DNA on tampons.

Photograph of Jamie N. Bakkum-Gamez, M.D., of Mayo Clinic

Jamie N. Bakkum-Gamez, M.D.

Researchers at Mayo Clinic have shown that it's possible to detect endometrial cancer using tumor DNA picked up by ordinary tampons.

The new approach specifically examines DNA samples from vaginal secretions for the presence of chemical off switches — known as methylation — that can disable genes that normally keep cancer in check.

The finding is a critical step toward a convenient and effective screening test for endometrial cancer, which is the most common gynecologic malignancy in the United States. Results of the endometrial cancer study were published in the April 2015 issue of Gynecologic Oncology.

"Unfortunately, there is no equivalent to a Pap smear or a mammogram for endometrial cancer," said Jamie N. Bakkum-Gamez, M.D., a gynecologic oncologist at Mayo Clinic in Rochester, Minnesota, and the study's lead investigator. "We know that the earlier a woman is diagnosed, the better the likelihood is that she is going to have a positive outcome from cancer treatment. Our goal is to use our findings to develop a tool for the early detection of endometrial cancer that women could use in the comfort of their own homes."

In most cases, women learn that they have endometrial cancer only after abnormal vaginal bleeding prompts a visit to the doctor. However, more insidious molecular changes take place long before such symptoms appear.

A small study published in 2004 showed that DNA samples collected from tampons were excessively methylated (hypermethylated) in women with endometrial cancer compared with women without the disease. However, in the years since, little progress has been made in turning that approach into a practical screening test.

"We wanted to take this initial study one step further and use advances in technology to see if we could develop a better method of differentiating between cancerous and benign cells," Dr. Bakkum-Gamez said.

First, Dr. Bakkum-Gamez and her colleagues obtained samples from 66 women who were about to undergo a hysterectomy, 38 because of endometrial cancer and 28 for other indications. Each woman used an intravaginal tampon to collect vaginal secretions and also underwent endometrial brushing, a procedure that uses a wire brush to scrape cells from the inner lining of the uterus.

The researchers isolated DNA from the samples and then analyzed 97 methylation sites along 12 different genes, half initially discovered by members of the research team and half previously reported by other researchers. They found that methylation was higher in specimens from women with endometrial cancer for nine of the 12 genes analyzed. The results were similar regardless of whether DNA was acquired through a tampon or endometrial brushing.

Researchers say they need to further refine their method before it can be used clinically. Dr. Bakkum-Gamez and her colleagues are now looking for additional genes that are mutated or methylated in the earliest stages of endometrial cancer.

Once they have the final lineup of genes to use in the test, they plan to validate the test using samples obtained through a clinical trial that is currently accruing 1,000 women at higher risk of endometrial cancer.