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Prognostic Impact of Prechemotherapy Serum Levels of HER2, CA125, and HE4 in Ovarian Cancer Patients
  1. Karina Dahl Steffensen, MD, PhD*,,
  2. Marianne Waldstrøm, MD,
  3. Ivan Brandslund, MD§ and
  4. Anders Jakobsen, MD, DMSc*,
  1. *Department of Oncology, Vejle Hospital, Vejle;
  2. Institute of Regional Health Services Research, University of Southern Denmark, Odense; and Departments of
  3. Pathology and
  4. §Clinical Biochemistry, Vejle Hospital, Vejle, Denmark.
  1. Address correspondence and reprint requests to Karina Dahl Steffensen, MD, PhD, Department of Oncology, Vejle Hospital, Kabbeltoft 25, DK-7100 Vejle, Denmark. E-mail: Karina.Dahl.Steffensen{at}


Objective: Human epididymis protein 4 (HE4) has attracted a lot of interest as a relatively novel biomarker for ovarian carcinoma. Research focus has been directed at HE4 as a diagnostic tool with potential for better triage of women with adnexal masses but the prognostic aspect of HE4 in ovarian cancer patients remains to be elucidated. The aim of the present study was to investigate the prognostic value of prechemotherapy serum HER2, cancer antigen 125 (CA125), and HE4 levels in ovarian cancer patients receiving standard combination chemotherapy.

Methods: Serum from 139 patients with newly diagnosed ovarian cancer was analyzed for HER2, CA125, and HE4 using enzyme-linked immunosorbent assay assays. Samples were collected just before first-line chemotherapy, and all patients were treated with carboplatin-paclitaxel combination chemotherapy.

Results: Increasing levels of serum HE4 (grouped into quartiles) was significantly associated with worse progression-free survival (PFS) (P < 10−5) and overall survival (P < 10−5). After adjustment in the Cox model, HE4 serum levels remained an independent prognostic parameter for PFS, with a hazard ratio of 1.77 (95% confidence interval, 1.03-3.04; P = 0.040) for patients with HE4 levels above the median compared with patients with HE4 levels below the median. The shorter PFS for patients with high levels of HE4 also translated into an independent significant difference in overall survival (hazard ratio, 3.17 [95% confidence interval, 1.41-7.10]; P = 0.005).

Serum HER2 and CA125 levels did not demonstrate an independent prognostic value.

Conclusions: High levels of serum HE4 is a strong and independent indicator of worse prognosis in epithelial ovarian cancer patients.

  • Ovarian cancer
  • HE4
  • CA125
  • HER2
  • Prognosis

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  • The study was supported by grants from Vejle Hospital and The Cancer Foundation.

  • The present article was also supported by Fujirebio Diagnostics AB and Siemens Medical Solutions Diagnostics AB, who kindly supported the present article by providing the kits for the CA125, HE4, and HER2 immunoassays.

  • The authors declare that there are no conflicts of interest.