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v-Raf Murine Sarcoma Viral Oncogene Mutation Status in Serous Borderline Ovarian Tumors and the Effect on Clinical Behavior
  1. Marjolijn B. Verbruggen, MD, PhD*,
  2. Nathalie L.G. Sieben, MD, PhD,
  3. Guido M.J.M. Roemen, PhD,
  4. Davy A.P. Rockx, BSc§,
  5. Paul J. van Diest, MD, PhD,
  6. René H.M. Verheijen, MD, PhD and
  7. Josephine C. Dorsman, PhD§
  1. * Department of Obstetrics and Gynaecology, VU University Medical Center, Amsterdam;
  2. Department of Histopathology, Academic Hospital Maastricht,Maastricht;
  3. Department of Pathology, University Medical Center Utrecht, Utrecht;
  4. § Department of Clinical Genetics, VU University Medical Center, Amsterdam; and
  5. Division of Surgical and Oncological Gynaecology, Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht, Utrecht, the Netherlands.
  1. Address correspondence and reprint requests to Josephine C. Dorsman, PhD, Section Oncogenetics, Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands. E-mail: JC.Dorsman{at}


Aims: To determine the incidence of activating v-raf murine sarcoma viral oncogene (BRAF) mutations in 30 serous borderline tumors (SBTs) of the ovary and the accompanying implants and to link BRAF mutation status to the clinical behavior of these tumors.

Methods and Results: Serous borderline tumors and noninvasive implants of 30 patients were analyzed for the presence of the BRAF V599E mutation, and mutation status was correlated to 70 months of clinical follow-up. Mutation status could be assessed in 27 SBTs. Eleven (41%) showed a BRAF mulation. Four (80%) of 5 patients with bilateral SBT showed a BRAF mutation in both ovaries. From the 8 implants that were analyzed for BRAF, 2 (25%) were mutated together with their primary tumor. v-Raf murine sarcoma viral oncogene mutation positive SBTs tend to present with a lower International Federation of Gynecology and Obstetrics stage and a higher tumor volume and are less frequently aneuploid. Seventy months' follow-up indicated no significant recurrence-free survival difference between these groups.

Conclusions: v-Raf murine sarcoma viral oncogene mutations are common in ovarian SBT, are strongly associated with bilateral tumors, and are also found in implants. A larger number of tumors should be investigated to assess clinical importance of BRAF mutation status in SBTs.

  • Borderline ovarian tumor
  • BRAF mutation
  • Clinical behavior
  • KRAS-BRAF kinase pathway

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