Women with postmenopausal bleeding generally undergo an invasive biopsy to look for endometrial cancer, but only 5% to 10% of patients with this symptom ultimately have an underlying malignancy.
New findings indicate that at-home screening tests can distinguish those women likely to have endometrial cancer from those who don’t and who can safely skip a biopsy.
A team of Dutch researchers reported that DNA methylation — a sign of cancer — detected in urine and cervicovaginal brush samples that women can collect at home is highly sensitive and specific for the disease. More specifically, methylation levels assessed using combinations of three genes demonstrated “excellent diagnostic performances,” with near-perfect areas under the receiver operating curve (AUC) for endometrial cancer detection.
Overall, “our study emphasizes the outstanding potential of DNA methylation analysis using patient-friendly home-based sample collection methods for endometrial cancer detection,” said the study investigators, led by Birgit M. M. Wever, a PhD candidate in pathology at Amsterdam UMC, the Netherlands.
DNA methylation testing “may contribute to the timely detection of endometrial cancer in patients with symptoms of postmenopausal bleeding” and with additional validation “could be valuable as a preselection method to inexpensively determine who needs to undergo invasive endometrial tissue sampling,” Wever and colleagues add.
The findings were published online March 13 in the International Journal of Cancer.
Detecting endometrial cancer early is important because advanced-stage disease is associated with a poor prognosis. Recent research indicates that endometrial cancer can be detected via DNA methylation signatures present in tumor cells shed in urine and vaginal fluids.
Using methylation-specific PCR, the team tested for methylation of nine genes associated with endometrial cancer in samples from 103 women with stage I-IV disease and 317 healthy control persons.
In addition to urine, women collected cervicovaginal samples at home using an Evalyn Brush from the Dutch company Rovers Medical Devices. Cervical scrapes were also collected in the clinic for testing.
Each gene showed significantly higher methylation levels in patients with cancer across all sample types.
Comparing the three screening methods, the team found that methylation of the GHSR, CDH13, and SST genes in urine samples had an AUC for endometrial cancer of 0.95; methylation of the GHSR, CDO1, and ZIC1 genes in at-home cervicovaginal brush samples had an AUC of 0.94; and methylation of CDH13, CDO1, and ZIC1 on cervical scrapes in the clinic had an AUC of 0.97.
“Excellent diagnostic performances were maintained” in the 72 women with stage I endometrial cancer, “confirming the ability to detect endometrial cancer at its earliest stage,” the investigators say.
The team noted a caveat to their findings. Because sample collection came after endometrial biopsy in patients with cancer, it is possible that the procedure released tumor DNA into urine and vaginal fluids. However, the median time between biopsy and self-sampling was 37 days, which means the biopsy procedures most likely had little bearing on the presence of tumor DNA, the researchers explain.
Although the findings need to be validated in women presenting with postmenopausal bleeding as well as in asymptomatic women at risk for endometrial cancer, the at-home screening tests appear to have “great potential to noninvasively screen patient populations at risk for endometrial cancer,” Wever and colleagues conclude.
Jamie Bakkum-Gamez, MD, an ob-gyn professor at the Mayo Clinic in Rochester, Minnesota, who was not involved in the research, noted that “this team is doing some exciting work” and “has identified a very promising molecular platform.”
Bakkum-Gamez, who is conductng similar research, has written a paper, which is under review, demonstrating strong results for detecting endometrial cancer through methylated DNA analysis of vaginal fluid collected via tampon.
For “most women with endometrial cancer, the bleeding will be painless; the symptom may be considered more of a nuisance and brushed off at first,” Bakkum-Gamez said. Being able a way to conveniently screen at home “has the potential to truly improve survival in endometrial cancer through earlier detection and earlier intervention.”
Jason Wright, MD, chief of gynecologic oncology at Columbia University, New York City, agreed that this at-home approach shows potential.
The methylation assays reported in the study represent “a promising technology to evaluate and potentially screen for endometrial cancer,” said Wright, who was not involved in the research. However, Wright also agreed with the authors that “these findings must be verified in larger studies of more diverse populations.”
The work was funded in part by the Hanarth Foundation and Weijerhorst Foundation. Wever has disclosed no relevant financial relationships. Two investigators reported minority shares in Self-screen BV, a company that holds patents and products related to methylation markers for cervical screening. Bakkum-Gamez is a named inventor on intellectual property rights for using methylated DNA markers to detect gynecologic cancers. Wright has disclosed no relevant financial relationships.
Int J Cancer. Published online March 13. Full text
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: [email protected].
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