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Early Endometrial Cancer Mutations Detectable in Uterine Lavage Fluid

Allie Strickler @Alliejayes
Published: Friday, Jan 13, 2017

John A. Martignetti, MD, PhD

John A. Martignetti, MD, PhD

As mortality rates continue to climb in endometrial cancer, there remains a pressing need for effective screening and diagnostics.

According to John A. Martignetti, MD, PhD, it is projected that, by 2030, endometrial cancer will become the third leading cancer for women.

The Cancer Genome Atlas (TCGA) carried out a comprehensive, genomics-based analysis of the disease, in which they revealed many of the molecular defects that define this cancer. Based on those findings, Martignetti and his colleagues hypothesized that ultra-deep, targeted gene sequencing may be able to detect somatic mutations in uterine lavage fluid obtained from patients undergoing hysteroscopy as a means of molecular screening and diagnosis.

In an interview with OncLive, Martignetti, an associate professor of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, and network director for the Laboratory for Translational Research at the Western Connecticut Health Network, discussed this novel genomic analysis and what impact the results could have in the detection, screening, and diagnosis of endometrial cancer.

OncLive: What was the rationale for conducting this genomic analysis?

Martignetti: If you think about endometrial cancer, it’s a cancer where there are 55,000 cases a year. And the incidence is actually increasing, so it’s projected by 2030, endometrial cancer will probably have the same number of cases as colorectal cancer for US women. It’ll become the third leading cancer site in women by 2030.

What really has not kept pace with those increasing numbers is any way to diagnosis it. Symptoms can include nonmenstrual bleeding, postmenopausal bleeding, pain, weight loss, back pain, things like that. But really, there’s no clinically useful molecular markers or diagnostics that are currently available. And really, the only way to make a diagnosis, the gold standard way, is to bring a patient into the OR, and do a hysteroscopy, and that really has not changed.

Clearly, to bring the patient into the OR, it’s a big deal because you’re talking about the pain, the cost, the time, the risks of general anesthesia, and then you’ve got issues of tissue sampling, depending on the age of the patient, whether there’s any structural abnormalities, and ultimately, the final interpretation of whether that patient has endometrial cancer or not. It’s really a subjective test in the sense that it’s a section of tissue sent for histology. There aren’t any special stains, no special markers; it’s really a subjective call. And depending on where you are, you may be blessed with a great pathologist, or maybe that’s something you don’t have adequately available.

But there are 2 other interesting forces here. One force is essentially, if you think about a pap smear, they were devised about 70 years ago, and the concept is to touch the cervix and look for cytologic changes that would suggest someone has cervical cancer. Since that test was devised, people have been trying to do a similar thing for endometrial cancer. For a number of reasons, it’s just never really worked out well.

A couple of years ago, some people came up with a clever test of using a tampon-like device to look for genetic changes that could be associated with endometrial cancer. It was fairly good, but it wasn’t great. Earlier this year, another group actually took patients with endometrial cancer and did this lavage procedure that we’ve done in our own study and showed that patients with endometrial cancer did have genetic changes that were discoverable in this lavage.

The other force that made this study timely was, a couple years ago, TCGA sequenced endometrial cancers, and from their sequencing of more than 400 patient samples, they showed that genetic changes within the tumors could predict outcome, and there were specific genes that were mutated in these cancers.

And what specifically did you do in your study?

What we did was different from what’s been done before. We took 102 women who were being diagnosed—in other words, their physicians were suspicious that the patients might have endometrial cancer because the women may have had postmenopausal bleeding, pain, they might have had ultrasound findings of a mass, but couldn’t sort out what it was exactly, but there was a suspicion that there could be cancer there, and they needed to get a hysteroscopy.




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