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Changes in Ki-67 Labeling Indices During Neoadjuvant Chemotherapy for Advanced Ovarian Cancer Are Associated With Survival
  1. Martin Pölcher, MD*,
  2. Nicolaus Friedrichs, MD,
  3. Christian Rudlowski, MD*,
  4. Rolf Fimmers,
  5. Mignon-Denise Keyver-Paik, MD*,
  6. Kirsten Kübler, MD*,
  7. Axel Sauerwald, MD*,
  8. Reinhard Büttner, MD,
  9. Walther Kuhn, MD* and
  10. Michael Braun, MD*
  1. *Department of Gynecology and Obstetrics, and
  2. Institute of Pathology, Center for Integrated Oncology, and
  3. Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Medical Center, Bonn, Germany. Mr Friedrichs is now with the Zentrale Klinische Forschung, University Freiburg, Freiburg, Germany.
  1. Address correspondence and reprint requests to Martin Pölcher, MD, Department of Gynecology and Obstetrics, Center for Integrated Oncology, University of Bonn Medical Center, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. E-mail: martin.poelcher{at}


Objective: To evaluate changes in Ki-67 expression during neoadjuvant chemotherapy (NACT) in advanced ovarian cancer.

Materials and Methods: Patients with International Federation of Gynecology and Obstetrics stage IIIC or IV and large-volume ascites were treated with NACT within a phase 2 trial. The expression of Ki-67 was evaluated by immunohistochemistry on paraffin-embedded tissue samples and classified by percentage of stained cells. Survival curves were plotted using the Kaplan-Meier method.

Results: Comparison of 40 individual paired results from pretreatment and posttreatment samples revealed a median difference of −0.11 in the Ki-67 index (95% confidence interval, −0.20 to −0.01; P = 0.005, signed rank test). Univariate analysis identified a high Ki-67 index as well as an increasing Ki-67 index after NACT as significant prognostic markers for progression-free survival (P = 0.004 and P = 0.001; log-rank test). Six of 12 patients with an increased Ki-67 index after NACT developed recurrence within 6 months after therapy.

Conclusions: Changes of the Ki-67 index during NACT are associated with progression-free survival. If confirmed in prospective trials, an increasing Ki-67 index during preoperative treatment may serve as an indicator for resistance to chemotherapy.

  • Ovarian cancer
  • Neoadjuvant chemotherapy
  • Ki-67
  • Prognostic factors

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  • Martin Pölcher and Nicolaus Friedrichs contributed equally to this work.