This article is more than 5 years old. Information may no longer be current.
Uterine lavage fluid analysis may be used as screening method for endometrial cancer
Researchers detected mutations associated with endometrial cancer in uterine lavage fluid of pre- and postmenopausal women, suggesting uterine lavage analysis may be useful for gynecologic cancer screening, according to results of a prospective cross-sectional study.
“Since a uterine lavage can be easily and quickly performed in a physician’s office, our initial idea was that this molecular approach could lead to early detection of precancerous and cancerous conditions of the uterus,” John Martignetti, MD, PhD, associate professor of genetics and genomic sciences at Icahn School of Medicine at Mount Sinai, told HemOnc Today. “However, these findings go beyond genetic screening since they have implications for both molecular diagnostics and raise previously unexplored questions into endometrial cancer development and its possible interruption.”
Currently, there are no screening methods available for the detection of premalignant lesions or early-stage endometrial cancer, a cancer that is increasing in both incidence and mortality in the United States, according to study researcher Peter Dottino, MD, director of gynecologic oncology at Mount Sinai Health System.
“We were therefore interested in the possibility of coupling newly developed genomic technologies with current treatment practices to develop a precision medicine assay for screening and early detection of this cancer,” Dottino said in a press release.
Researchers conducted next-generation sequencing on uterine lavage and paired blood samples from 107 women (mean age, 57.5 years; range, 29 to 85) undergoing hysteroscopy and curettage due to postmenopausal uterine bleeding or abnormal pelvic ultrasound results. The lavage fluid was separated into cellular and acellular fractions by centrifugation, and the cellular and cell-free DNA were isolated from each lavage.
Analysis showed seven patients had endometrial cancer based upon histopathological evidence, and all of these patients — including six who had small, microscopic evidence of cancer — had significant cancer-driver gene mutations detected in their uterine lavage fluid.
Analysis of four of these patients with adequate tumor samples showed all mutations above a specific allele fraction also were present in the uterine lavage DNA samples. Further, mutations thought only to be found in the lavage fluid were later detected in the tumor samples at allele fractions significantly less than 1%.
Another 95 women were diagnosed with benign or noncancer pathology, 44 of whom had no mutations detected.
However, 51 patients with no histopathological evidence of cancer each carried high allele fraction (1%-30.4%) cancer-associated mutations in the cells or the cell-free DNA from their lavage fluid.
Because of this, uterine lavage fluid alone was not able to differentiate between women with and without clinically relevant evidence of endometrial cancer. Therefore, Martignetti said caution needs to be taken.
“We detect these cancer mutations even in a subpopulation of women who do not have histopathologically detectable cancer,” he said. “Have we detected precancerous lesions or uncovered something unknown about how genetic lesions develop but somehow are not enough to lead to cancer development?”
The likelihood of harboring mutations increased with older age (mean age mutated, 57.96 years; mean age no mutations, 50.35 years; P = .002) and postmenopausal status (P = .004).
The basis for screening is possible, but not yet translatable to the clinic, Martignetti said. Additional research is required to understand the significance of driver mutations in women without evidence of cancer to determine whether and how these precancerous mutations can lead to cancer.
“The next phase of our ongoing research with 1,000 women enrolled from across multiple institutions will help us to begin sorting out these questions which will ultimately be key to improving upon cancer care,” Martignetti said. – by Melinda Stevens
For more information:
John A. Martignetti , MD, PhD, can be reached at john.martignetti@mssm.edu.
Disclosure: Martignetti and another researcher report funding from the Gordon family, the Derald H. Ruttenberg Foundation and the Varadi Ovarian Initiative in Cancer Education. Three other researchers report employment with Swift Biosciences.