Research shows promise vs. uterine cancer

January 9, 2017

DANBURY - An unsuccessful effort to find a screening test for uterine cancer led one researcher to a discovery so intriguing that it might teach medicine more about how cancer starts - and perhaps why it doesn’t.

If the discovery sounds accidental, it was.

“We found this landscape of mutations that no one had ever seen before - probably because no one had ever looked,” said Dr. John Martignetti, a cancer geneticist at the Icahn School of Medicine at Mount Sinai in Manhattan, and the Director of the Western Connecticut Health Network’s Laboratory for Translational Research. “Does it have something to do with the immune system? Or something we still don’t know about cancer genetics? We don’t know.”

Martignetti and his colleagues discovered to their surprise during a study of 100 women that genes known to cause cancer had mysteriously not developed into cancer.

“These women were developing the early stages of cancer, but it stopped,” said Martignetti, whose research was published in the peer-reviewed journal PLOS Medicine in December. “If you put these genes in mice, the cells continue onto a cancerous pathway, but in these women these mutations were somehow stopping.”

To appreciate how the unexpected occurred, and why Martignetti is so hopeful about a 1,000-woman study he’s proposed to explore the new landscape, it’s helpful to understand some background about 10th leading type of cancer in America.

About 55,000 women will develop cancer of the uterus this year - four times as many as will develop cervical cancer — yet there is no blood test to detect uterine cancer. Symptoms include abnormal bleeding and uterine pain.

“In Mount Sinai we are getting about 10 cases a week,” Martignetti said. “Just in Danbury alone, we are getting about two cases a week.”

A probe procedure that allows physicians to take samples from the uterus is the industry detection standard, but the method does not detect cancer in every case because it relies on a pathologist with a microscope to make the correct diagnosis.

“We don’t think it’s the pathologist’s fault,” Martignetti said. “It’s just that you are looking at tissue and trying to guess its behavior.”

Martignetti’s idea was to use a recent breakthrough in cancer genetics at the National Institutes of Health known as the Cancer Genome Atlas to match the DNA of uterine cancer with samples from patients.

At first Martignetti and his colleagues were elated by the results. Seven of the women in the study had uterine cancer - six of them its earliest possible detection stage.

“The hopeful part was we could detect really small millimeter-sized microscopic cancer,” said Martignetti, who joined the health network that runs Danbury, New Milford and Norwalk hospitals in November.

But then the unexpected happened.

“Half of the women who went into this procedure who did not have cancer also had these mutations,” Martignetti said. “That one was the real head-scratcher.”

The surprise results mean two things:

More clinical study is needed to find a screening test for uterine cancer that does not give a false positive.

More clinical study is needed to understand why known cancer drivers stop short of becoming cancer.

Martignetti hopes to get funding in place soon for a major study of 1,000 women that will pursue both fields of study.

“It’s a new landscape we didn’t know about, but it is making sense with what some other researchers are finding,” Martignetti said. “So we are pretty excited.”

rryser@newstimes.com; 203-731-3342