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The role of HE4 for prediction of recurrence in epithelial ovarian cancer patients—results from the OVCAD study

Tumor Biology volume 37, pages 3009–3016 (2016)Cite this article

Abstract

Patients with epithelial ovarian cancer (EOC) are at high risk of tumor recurrence. Human epididymis protein 4 (HE4) has been shown to be overexpressed in EOC. The primary aim of our study was to evaluate the role of HE4 in predicting recurrence in EOC patients. Furthermore, we assessed the role of HE4 in predicting recurrence after second-line chemotherapy. We retrospectively analyzed data of 92 out of 275 primary EOC patients of the multicenter project “Ovarian Cancer: Diagnosis of a silent killer” (OVCAD). The concentrations of HE4 and CA125 were determined preoperatively and 6 months after the end of platinum-based first-line chemotherapy (FU) using ELISA and Luminex technique, respectively. The role of HE4 and CA125 for prediction of recurrence was determined using receiver operating characteristics (ROC) curves. Out of 92 patients included, 70 (76 %) were responders and 22 (23 %) non-responders in terms of response to platinum-based first-line chemotherapy. Median HE4 concentrations at follow-up (FU) differed between responders and non-responders (60.5 vs. 237.25 pM, p = 0.0001), respectively. The combined use of HE4 and CA125 at FU with cut-off values of 49.5 pM and 25 U/ml for HE4 and CA125, respectively, for predicting recurrence within 12 months after first-line chemotherapy performed better than HE4 or CA125 alone (area under the curve (AUC) 0.928, 95 % confidence intervals (CI) 0.838–1, p < 0.001). HE4 at FU could predict recurrence within 6 months after second-line chemotherapy (AUC 0.719, 95 % CI 0.553–0.885, p = 0.024). The combination of both elevated biomarkers revealed significantly worse estimated median progression-free survival (PFS; hazard ratio (HR) 8.14, 95 % CI 3.75–17.68, p < 0.001) and slightly worse PFS in those in whom only one biomarker was elevated (HR 1.46, 95 % CI 0.72–2.96, p = 0.292) compared to those patients in whom no biomarker was elevated. For the estimated median overall survival (OS), our analysis revealed similar results. HE4 in combination with CA125 performed better than CA125 and HE4 alone in predicting recurrence within 12 months after first-line chemotherapy.

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Acknowledgments

This work is part of a Master’s thesis of the Master’s Program in Clinical Research, Center for Clinical Research and Management Education, Division of Health Care Sciences, Dresden International University, Dresden, Germany. Dr. Elena Ioana Braicu is a participant of the Charité Clinical Scientist Program funded by the Charité Universitätsmedizin Berlin and the Berlin Institute of Health.

Conflicts of interest

This study was performed within the OVCAD FP6 European Project. The sample analysis was performed by Fujirebio Diagnostics AB, Sweden. Christina Hall is an employee of Fujirebio Diagnostics AB in Sweden. Dr. Elena Ioana Braicu is a participant of the Charité Clinical Scientist Program funded by the Charité Universitätsmedizin Berlin and the Berlin Institute of Health. The other authors declare no conflicts of interest in regard to the present study.

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Affiliations

  1. Department of Gynecology, Tumor Bank Ovarian Cancer (TOC), European Competence Center for Ovarian Cancer, Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Mani Nassir, Jun Guan, Hrvoje Luketina, Irena Rohr, Rolf Richter, Jalid Sehouli & Elena Ioana Braicu

  2. Center for Clinical Research and Management Education, Division of Health Care Sciences, Dresden International University, Dresden, Germany

    Mani Nassir & Timo Siepmann

  3. Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    Timo Siepmann

  4. Molecular Oncology Group, Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria

    Dan Cacsire Castillo-Tong & Robert Zeillinger

  5. Ludwig Boltzmann Cluster Translational Oncology, General Hospital of Vienna, Vienna, Austria

    Robert Zeillinger

  6. Division of Gynaecological Oncology, Department of Obstetrics and Gynaecology, Leuven Cancer Institute, University Hospitals Leuven, Katholieke Universiteit Leuven, Leuven, Belgium

    Ignace Vergote & Els Van Nieuwenhuysen

  7. Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria

    Nicole Concin & Christian Marth

  8. Fujirebio Diagnostics AB, Gothenburg, Sweden

    Christina Hall

  9. Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Sven Mahner & Linn Woelber

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  1. Mani Nassir
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  2. Jun Guan
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  7. Dan Cacsire Castillo-Tong
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  11. Nicole Concin
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  13. Christina Hall
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  14. Sven Mahner
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  15. Linn Woelber
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  16. Jalid Sehouli
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  17. Elena Ioana Braicu
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Correspondence to Mani Nassir.

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Nassir, M., Guan, J., Luketina, H. et al. The role of HE4 for prediction of recurrence in epithelial ovarian cancer patients—results from the OVCAD study. Tumor Biol. 37, 3009–3016 (2016). https://doi.org/10.1007/s13277-015-4031-9

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  • DOI: https://doi.org/10.1007/s13277-015-4031-9

Keywords

  • HE4
  • CA125
  • Prediction
  • Recurrence
  • Epithelial ovarian cancer