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The Role of HE4 in Ovarian Cancer Follow-up: A Review
  1. Elisa Piovano, MD*,
  2. Lorenza Attamante, MD*,
  3. Chiara Macchi, MD*,
  4. Camilla Cavallero*,
  5. Cesare Romagnolo, MD,
  6. Tiziano Maggino, MD,
  7. Fabio Landoni, MD§,
  8. Angiolo Gadducci, MD,
  9. Enrico Sartori, MD,
  10. Massimo Gion, MD# and
  11. Paolo Zola, MD*
  1. *Department of Surgical Sciences, University of Turin, Turin;
  2. Unit of Gynaecology and Obstetrics, G. Fracastoro Hospital, San Bonifacio, Verona;
  3. Unit of Obstetrics and Gynaecology, Dell’Angelo Hospital, Mestre-Venice;
  4. §Department of Gynecology, Cervical Cancer Center, European Institute of Oncology, Milan;
  5. Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa;
  6. Department of Obstetrics and Gynaecology, University of Brescia, Brescia; and
  7. #Regional Centre for Biomarkers, Department of Clinical Pathology, Campo SS. Giovanni e Paolo, Venice, Italy.
  1. Address correspondence and reprint requests to Elisa Piovano, MD, Department of Surgical Sciences, University of Turin, Via Ventimiglia 3, 10126 Turin, Italy. E-mail: piovano.elisa{at}


Objective The aim of this review was to analyze the state of the art about HE4 and follow-up in patients treated for ovarian cancer.

Methods A literature search was conducted in the MEDLINE database using the key words “HE4” and “ovarian cancer” and “recurrence” or “relapse” or “follow up.”

Results Seven of 28 clinical studies were selected. Four studies were prospective, and all of them were based on a small number of patients (8–73 women). A failure of HE4 levels to normalize at completion of standard therapy may indicate a poor prognosis, thus suggesting the need of a closer follow-up. Moreover, HE4 showed better sensibility and specificity in the diagnosis of ovarian cancer recurrence with respect to CA-125, being also an earlier indicator of the relapse with a lead time of 5 to 8 months. HE4 showed a better performance in this setting if performed in association with other markers (CA-125, CA-72.4). HE4 seems to be an independent predictive factor for the surgical outcome at secondary cytoreductive surgery and to maintain its prognostic role even after the recurrence.

Conclusions These preliminary data start to suggest a superiority of HE4 over CA-125 in the detection of ovarian cancer recurrence. Moreover, the prognostic role of HE4 could help clinicians to personalize the follow-up program, whereas its predictive role could be useful to plan the treatment of the relapse. The role of HE4 in ovarian cancer follow-up deserves to be further investigated in prospective randomized multicentric studies.

  • HE4
  • Ovarian cancer
  • Follow-up
  • Recurrence
  • CA-125

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  • The authors declare no conflicts of interest.