The role of HE4 in ovarian cancer follow-up: A review

Elisa Piovano, Lorenza Attamante, Chiara Macchi, Camilla Cavallero, Cesare Romagnolo, Tiziano Maggino, Fabio Landoni, Angiolo Gadducci, Enrico Sartori, Massimo Gion, Paolo Zola

Research output: Contribution to journalArticlepeer-review


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 (8Y73 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.

Original languageEnglish
Pages (from-to)1359-1365
Number of pages7
JournalInternational Journal of Gynecological Cancer
Issue number8
Publication statusPublished - Oct 1 2014


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

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology
  • Medicine(all)


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