Πέμπτη, 5 Ιανουαρίου 2017

ENDOMETRIAL CANCER DETECTED IN ENDOMETRIAL LAVAGE FLUID

Genetic analysis of endometrial lavage fluid may be a way to identify early-stage endometrial cancer, and it could also identify a precancer or a cancer-prone uterine environment, researchers suggest. But the test is not yet ready for the clinic, they say.
The findings, from a study conducted in a group of pre- and postmenopausal women undergoing diagnostic hysteroscopy, were published online December 27, 2016, in PLOS Medicine.
The researchers found that targeted genetic sequencing of uterine lavage fluid identified cancer driver mutations in all women found to have early-stage endometrial cancer. About 50% of women with benign disease also had driver mutations, raising the question as to whether genetic tests can identify precancer or a cancer-prone uterine environment.
"The technology is so sensitive that we can detect mutations from tumors that are microscopic in size and are still stage I cancers," lead author Jonathan Martignetti, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York City, told Medscape Medical News.
Currently, there are no effective screening methods for endometrial cancer, which represents the most common gynecologic cancer in women. The incidence and mortality rate from endometrial cancer are increasing in the United States.
Postmenopausal bleeding is one of the few clinical signs of endometrial cancer, but only about 5% to 10% of older women who go to their gynecologist with abnormal bleeding have cancer. Having a way to screen for and detect early-stage endometrial cancer could potentially improve the care of many women, Dr Martignetti commented.
Scientists have known for more than 70 years that endometrial cancer cells are shed into the uterine cavity. However, past studies involving the use of these cells for cancer detection have included only women who had already been diagnosed with cancer. The new study differs from past studies because it looked prospectively at women who had not yet been diagnosed with cancer.
Study Details
The study included 107 women with abnormal bleeding or abnormal pelvic ultrasound findings. The patients underwent hysteroscopy and uterine lavage, the gold standard for diagnosing endometrial cancer.
Researchers used a 56-gene panel and a 12-gene panel of known cancer driver genes to analyze cellular DNA and cell-free DNA in the lavage fluid. They also conducted a standard histopathologic analysis of the samples.
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About 50% (n = 51) of women without histopathologic evidence of cancer were also found to have cancer-driver mutations in their lavage fluid.
Women with driver mutations were significantly older than women without driver mutations (P = .002). They were also more likely to be postmenopausal in comparison with the women who did not have driver mutations (P = .004).
The really interesting part of this study is that about 50% of the women who by histopathology had benign disorders or no evidence of cancer had mutations," Dr Martignetti said.
This brings up the question, did the genetic tests detect precancerous lesions or identify a cancer-prone "landscape" in some women who are somehow able to keep cancer from developing or halt its progression?
By discovering a previously unrecognized cancer gene mutation landscape in women both with and without cancer, this work represents a powerful opportunity to gain new insights into why some women remain healthy and cancer free while others succumb to this disease," commented Eric Schadt, PhD, founding director of the Icahn Institute for Genomics and Multiscale Biology at Mt. Sinai and head of the department where much of the research took place.
"Understanding why some women remain resilient to developing endometrial cancer has implications not only for this cancer but may possibly lead to greater understanding across many cancers," Dr Schadt added in a statement.
Although the study suggests that genetic testing could form the basis of screening for endometrial cancer, the technology is not yet translatable to the clinic.
"The sensitivity is there, but the specificity isn't there yet. It's obviously not ready for the clinic, but it's a great research tool for right now," Dr Martignetti told Medscape Medical News.
"As we start applying these cancer mutation screening programs, we may come up with a lot of findings that are really too soon for translation into the clinic. We're going to be detecting mutations, but that doesn't mean that that person has a clinical disease yet," he added.
The researchers plan to follow this group of women over time to see who develop cancer. They have also started a new study that will include 1000 women from multiple institutions. They plan to increase the variables in the genetic panels to evaluate whether other factors may be associated with these genes and to improve the test's specificity.
Jonathan Martignetti and Peter Dottino received funding from the Gordon family, the Derald H Ruttenberg Foundation, and the Varadi Ovarian Initiative in Cancer Education (VOICE).Timothy Harkins, Cassie Schumacher, and Jonathan Irish are employees of Swift Biosciences.
PLoS Med. Published online December 27, 2016. Full text

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