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Uterine Cancer
GALR1 Methylation in Vaginal Swabs Is Highly Accurate in Identifying Women With Endometrial Cancer
  1. Konstantinos Doufekas, MBChB*,
  2. Richard Hadwin, BM*,†,
  3. Raju Kandimalla, PhD*,
  4. Allison Jones, BSc*,
  5. Tim Mould, MD*,
  6. Susanna Crowe, MBBS*,
  7. Adeola Olaitan, MD*,
  8. Nicola Macdonald, MD*,
  9. Heidi Fiegl, PhD‡,
  10. Elisabeth Wik, MD§∥,
  11. Helga B. Salvesen, MD, PhD§∥ and
  12. Martin Widschwendter, MD*
  1. *Department of Women’s Cancer, University College London Elizabeth Garrett Anderson Institute for Women’s Health, University College London, United Kingdom;
  2. †Department of Gynaecological Oncology, University Hospital Southampton, United Kingdom;
  3. ‡Department of Gynaecology and Obstetrics, Innsbruck Medical University, Innsbruck, Austria;
  4. §Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway; and
  5. ∥Department of Clinical Science, University of Bergen, Norway.
  1. Address correspondence and reprint requests to Martin Widschwendter, MD, Department of Women’s Cancer, UCL EGA Institute for Women’s Health, University College London, Medical School Building, Room 340, 74 Huntley St, London WC1E 6AU, United Kingdom. E-mail: M.Widschwendter@ucl.ac.uk.

Abstract

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%.

  • Epigenetics
  • DNA methylation
  • Endometrial cancer
  • Vaginal swab
  • Postmenopausal bleeding

https://doi.org/10.1097/IGC.0b013e3182959103

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    Footnotes

    • Konstantinos Doufekas, Richard Hadwin, and Raju Kandimalla contributed equally to this work.

    • This work was funded by the Eve Appeal ( http://www.eveappeal.org.uk/) and a grant from the UCLH/UCL Comprehensive Biomedical Research Centre project, and by the NIHR Health Technology Assessment Programme, and the work has been undertaken at UCLH/UCL, which received a proportion of its funding from the Department of Health NIHR Biomedical Research Centres (BRC) funding scheme. Additional funding came from the EGA Trustees. H. B. Salvesen received support from Helse Vest, Research Council of Norway, and The Norwegian Cancer Society (Harald Andersens legat). This pan-European collaboration was supported by the European Network Translational Research in Gynaecological Oncology (ENTRIGO) and the European Network of Individualized Treatment of Endometrial Cancer of the European Society of Gynaecological Oncology (ESGO).

    • The authors declare no conflicts of interest.