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Ki67 expression as a predictor of chemotherapy outcome in low-grade serous ovarian cancer
  1. Jacek P Grabowski1,
  2. Clara Martinez Vila2,
  3. Rolf Richter1,
  4. Eliane Taube3,
  5. Helmut Plett1,4,
  6. Elena Braicu1 and
  7. Jalid Sehouli1
  1. 1Department of Gynecology with Center of Oncological Surgery, Virchow Campus Clinic, Charite Universitatsmedizin Berlin, Berlin, Germany
  2. 2Department of Medical Oncology, Hospital Clinic de Barcelona, Barcelona, Spain
  3. 3Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany
  4. 4Department of Gynecology and Gynecologic Oncology, Kliniken-Essen-Mitte, Essen, Germany
  1. Correspondence to Dr Jacek P Grabowski, Department of Gynecology, Charite Universitatsmedizin Berlin, Berlin 13353, Germany; jacek.grabowski{at}


Objective Low-grade serous ovarian cancers characterize a unique clinical pattern and lower chemotherapy responsiveness. The expression level of Ki67 is associated with differences in prognosis; however, this has not yet been evaluated in regard to predicting the outcome of therapy.

Methods Patients with low-grade serous ovarian cancers were identified in an institutional database. Receiver-operator characteristics (ROC) curve analysis was performed to find cut-off values of Ki67 to discriminate patients with residual tumor mass after surgery from maximal debulked patients: therapy response and therapy-free interval (TFI).

Results A total of 68 patients with low-grade serous ovarian cancer were identified. All patients underwent surgery. 61 (89.7%) patients received platinum-based first-line chemotherapy; of these 61 patients, 13 (21.3%) had residual mass (>0 mm) after primary cytoreduction and 11 (18%) received neo-adjuvant chemotherapy. Ki67 ≥3.6% was associated with higher risk of residual mass after surgery (OR 8.1, 95% CI 1.45 to 45.18; p=0.017). Patients with Ki67 <3.6% showed a therapy-free interval of ≥6 months more often (OR 13.9, 95% CI 1.62 to 118.40; p=0.016). In the multivariate analysis of TFI <6 months, including CA125, age at diagnosis, peritoneal carcinomatosis, and ascites, Ki67 <3.6% remained a significant prognostic factor (OR 18.8, 95% CI 1.77 to 199.09; p=0.015). Chemotherapy responsiveness was evaluated in 21 patients who had residual disease and/or received neo-adjuvant chemotherapy. Ki67 ≥4.0% (OR 44.1, 95%CI 2.36-825.17, p = 0.011) was related to a significantly higher response rate (complete and partial response).

Conclusions This is the first study to show an association between Ki67 expression and chemotherapy response, duration of TFI to platinum-based chemotherapy as well as outcome of surgery in low-grade serous ovarian cancers. Further prospective trials should use Ki-67 as a stratification factor to explore the effect of chemotherapy and endocrine strategies.

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  • Contributors Guarantor of the integrity of the study: JPG, JS, CMV. Study concepts: JPG, JS. Study design: JPG, JS. Definition of intellectual content: JPG, JS, EB, ET. Literature research: JPG, CMV. Clinical studies: JPG, CMV, ET, EB, HP, JS. Data acquisition: JPG, CMV, RR, EB, ET. Analysis: JPG, CMV, RR, JS. Statistical analysis: JPG, RR, CMV, JS. Manuscript preparation: JPG, CMV, JS. Manuscript editing: JPG, CMV, JS. Manuscript review: JPG, CMV, JS, RR.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No data are available. NA.