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Examining the Uterine Lavage Fluid for Early Signs of Endometrial Cancer

Surabhi Dangi-Garimella, PhD
According to a new study published in PLOS Medicine, genetic analysis of the uterine lavage fluid from pre- and post-menopausal women can provide early evidence of endometrial cancer.
The most common gynecologic cancer, the incidence and mortality associated with endometrial cancer has been on the rise. However, an effective screening method for this disease is lacking. Research conducted at the Icahn School of Medicine could change this. According to the study, genetic analysis of the uterine lavage fluid from pre- and post-menopausal women could provide early evidence of this cancer.

According to Peter Dottino, MD, director of Gynecologic Oncology at Mount Sinai Health System and one of the senior authors on the study, “Today, there are no effective screening methods for endometrial cancer, which is increasing in both incidence and mortality in the United States. 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.”

The study, published in PLOS Medicine, collected blood samples and uterine lavage from 107 patients who had hysterectomy and curettage for diagnostic evaluation. The lavage samples—processed to generate cellular and cell-free (cf) DNA—underwent next-generation sequencing using 2 gene panels (56 genes and 12 genes). The hysteroscopy samples were simultaneously analyzed using standard histopathology techniques.

Seven patients were diagnosed with endometrial cancer based on histopathologic analysis, 6 of whom had stage IA cancer; 1 cancer was detectable only as a microscopic focus within a polyp. Genetic analysis found all 7 patients had significant cancer-associated mutations in the cell pellet as well as the cfDNA. Patients whose tumor samples were not available in sufficient quantities had their lavage samples tested; all tumor mutations above a specific allele fraction were found in the lavage DNA samples, the authors write. Of the remaining 95 patients who had benign or non-cancer pathology, 51 had high allele fraction, cancer-associated mutations, which were not detected by histopathologic analysis.

“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 pre-cancerous and cancerous conditions of the uterus,” said senior author John Martignetti, MD, PhD, 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 Western Connecticut Health Network. However, he said that their findings now provide clues to not just an earlier diagnostic test, but also raise questions about disease development and intervention, which the authors plan to explore in another ongoing trial that has enrolled 1000 women across multiple institutions.

“Given that a uterine lavage can be easily and quickly performed even outside of the operating room and in a physician’s office-based setting, our findings suggest the future possibility of this approach for screening women for the earliest stages of endometrial cancer,” the authors concluded in their paper.

Reference

Nair N, Camacho-Vanegas O, Rykunov D, et al. Genomic analysis of uterine lavage fluid detects early endometrial cancers and reveals a prevalent landscape of driver mutations in women without histopathologic evidence of cancer: a prospective cross-sectional study. PLOS Med. 2016;13(12):e1002206. doi: 10.1371/journal.pmed.1002206.

 
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