Endometrial cancer (EC) is the most common gynecologic malignancy in the United States and in many other developed countries. Women with EC detected at an early stage have a higher likelihood of being cured of their cancer. Early detection also lowers the likelihood of needing additional treatment, such as radiation and/or chemotherapy after surgery.
A recent study by Mayo Clinic researchers, published in Gynecologic Oncology, aims to demonstrate the feasibility of detecting EC by combining minimally invasive specimen collection techniques with sensitive molecular testing.
Before diagnosis of EC, many women experience prolonged irregular bleeding prior to the development of advanced cancer. According to previous research, up to 25 percent of women who develop EC are diagnosed with a precursor lesion, endometrial hyperplasia, between one to 20 years prior to their EC diagnosis. This indicates that there is an opportunity to identify at-risk women with early detection methods.
According to Jamie Bakkum-Gamez, Mayo Clinic consultant of gynecologic surgery and first author of this paper, “The earlier an EC is detected, the lower the mortality risk of the cancer and the lower the morbidity is of the treatment.”
In developing the test, Mayo Clinic wanted to create a collection method that was easy for women to accept.
“Since the common tampon is a highly accepted hygiene product, we started by centering our test around the patient,” said Dr. Bakkum-Gamez.
Mayo determined the initial panel of genes to be tested based on what was in the literature as methylated genes reported in gynecologic cancers at the time the trial started. Novel genes were also added, which were identified by Mayo’s collaborators at the NCI using the Illumina GoldenGate platform. 97 CpGs within 12 genes were evaluated overall. Mayo decided to use pyrosequencing on the tampon DNA to detect methylation as Mayo has expertise in using this method.
The study results indicate that, overall, there are significantly higher rates of DNA methylation in EC compared to benign endometrium among nine of the 12 genes tested. By picking up these methylation differences in biospecimens collected using the common intravaginal tampon, the study enabled detection of primary tumor changes in the downstream effluent of the female reproductive tract.
“If one CpG site is methylated, most if not all of the CpG sites within that gene are also methylated, which means we should be able to simplify the test per gene to focus on 1-2 CpGs/gene,” said Dr. Bakkum-Gamez.
The overall methylation rates were higher in EC, however, there was overlap between the level of methylation among some of the ECs and benign endometrium, which tells indicates the gene panel needs refinement.
While self-collection of a vaginal tampon biospecimen is the ultimate goal and a feasible one, Mayo is centering its efforts around the patient to develop a test that is well-accepted by women and one that could be done in the comfort of their own home.
Based on this pilot study, Mayo identified genes that will likely be retained in the final early detection/screening test. It was also determined that there is still work to be done to improve the sensitivity of this test to detect 100 percent of ECs and precancerous endometrial lesions.
“Most importantly, we learned that tailoring our research and test development so that the ultimate test developed is acceptable and easy for a patient to use is critical and that the common tampon is a biospecimen collection device that is highly accepted by women,” said Dr. Bakkum-Gamez.