Article Text

Download PDFPDF
Role of human epididymis protein 4 (HE4) in detecting recurrence in CA125 negative ovarian cancer patients
  1. Francesco Plotti1,
  2. Federica Guzzo1,
  3. Teresa Schirò1,
  4. Corrado Terranova1,
  5. Carlo De Cicco Nardone1,
  6. Roberto Montera1,
  7. Daniela Luvero1,
  8. Giuseppe Scaletta2,
  9. Salvatore Lopez1,
  10. Stella Capriglione1,
  11. Pierluigi Benedetti Panici3 and
  12. Roberto Angioli2
  1. 1 Università Campus Bio-Medico di Roma Facolta di Medicina e Chirurgia, Roma, Italy
  2. 2 Obstetrics and Gynecology, Gynecology Oncology Unit. Department of Women's and Children's Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy, Rome, Italy
  3. 3 Department of obstetrics and gynecology, La Sapienza University of Rome, Roma, Italy
  1. Correspondence to Dr Federica Guzzo, Gynecology, Universita Campus Bio-Medico di Roma, Roma, Italy; f.guzzo{at}


Objective There are no current guidelines regarding evaluation of patients with normal CA125 at initial diagnosis during routine surveillance after completion of treatment. Thus, the purpose of this study was to evaluate the role of human epididymis protein 4 (HE4) in the detection of recurrence in patients with ovarian cancer and a negative CA125 at diagnosis.

Methods All patients with ovarian cancer with a negative CA125 referred to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome were included in the study. Inclusion criteria were: age between 18 and 70 years old, diagnosis of epithelial ovarian cancer, optimal primary surgery (residual tumor <1 cm), and normal CA125 at initial diagnosis. Patients with other malignancies or chronic diseases were excluded from the study. Statistical analysis was based on the calculation of percentages, means, medians, and ranges of the values.

Results A total of eight patients were included in the study. The median age was 53 years (range 40–75). All patients had a normal CA125 at initial diagnosis while seven (87.5%) patients had abnormal HE4 levels at diagnosis. The International Federation of Gynecology and Obstetrics (FIGO) stages at enrollment varied from IC to IIIC (IB (1), IC (3), IIC (1), IIIC (3)). The most common histologic subtype was serous (62.5%). Seven patients recurred and had abnormal HE4 and normal CA125 values. The median HE4 at recurrence was 107 pmol/L. The median disease-free interval was 55 months (range 5–108) and all the patients underwent optimal cytoreductive surgery.

Conclusions HE4 levels may serve as a marker for recurrence in patients with a normal CA125 at initial diagnosis. Future studies are needed to evaluate the role of HE4 levels in earlier detection of recurrent ovarian cancer.

  • ovarian cancer

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors FP contributed as main planner and researcher. FG and TS contributed in the conduction of the research and in the analysis of data. All the others authors contributed in data collection and revision of the article.

  • 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.