title: GALR1 methylation in vaginal swabs is highly accurate in identifying women with endometrial cancer.
abstract: Endometrial cancer has become the most common gynecological cancer in developed countries. Postmenopausal bleeding is indicative of the disease in only 1 of 10 women with this symptom. A noninvasive tool to identify women with cancer would be highly desirable. We analyzed more than 27,000 CpGs in normal endometrial tissue (n = 23) and endometrial cancers (n = 64) and found that DNA methylation of GALR1 is among the most frequent epigenetic alterations in this cancer. We then developed a real-time polymerase chain reaction-based GALR1 methylation test and applied this test to vaginal swabs from 79 women who presented with postmenopausal bleeding. The receiver operating characteristics area under the curve, describing sensitivity and specificity to correctly identify the 41 women with both premalignant and malignant endometrial changes, was 0.93 (95% confidence interval, 0.87-0.97; P < 0.0001).GALR1 DNA methylation is one of the most common molecular alterations in endometrial cancer, and the presence of GALR1 methylation in vaginal swabs from women with postmenopausal bleeding indicates the presence of endometrial malignancy with a sensitivity of 92.7% and a specificity of 78.9%.
authors.affiliation: Department of Women's Cancer, University College London Elizabeth Garrett Anderson Institute for Women's Health, University College London, United Kingdom.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Doufekas
authors.forename: Richard
authors.initials: R
authors.lastname: Hadwin
authors.forename: Raju
authors.initials: R
authors.lastname: Kandimalla
authors.forename: Allison
authors.initials: A
authors.lastname: Jones
authors.forename: Tim
authors.initials: T
authors.lastname: Mould
authors.forename: Susanna
authors.initials: S
authors.lastname: Crowe
authors.forename: Adeola
authors.initials: A
authors.lastname: Olaitan
authors.forename: Nicola
authors.initials: N
authors.lastname: Macdonald
authors.forename: Heidi
authors.initials: H
authors.lastname: Fiegl
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wik
authors.forename: Helga B
authors.initials: HB
authors.lastname: Salvesen
authors.forename: Martin
authors.initials: M
authors.lastname: Widschwendter
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis* / Q000235:genetics; D019175:DNA Methylation; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000235:genetics; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017698:Postmenopause; D011379:Prognosis; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D044091:Receptor, Galanin, Type 1 / Q000235:genetics*; D012680:Sensitivity and Specificity; D014626:Vaginal Smears
chemical_list: D044091:Receptor, Galanin, Type 1