HE4 expression in plasma correlates with surgical outcome and overall survival in patients with first ovarian cancer relapse

Ann Surg Oncol. 2014 Mar;21(3):955-62. doi: 10.1245/s10434-013-3347-1. Epub 2013 Nov 12.


Background: Epithelial ovarian cancer (EOC) remains the main cause of mortality due to gynecological malignancies. Optimal tumor debulking and platinum response are the most important prognostic factors for overall survival (OS) in primary EOC. In the setting of recurrence, the role of cytoreduction is not clear. A critical point is to predict preoperatively the subgroup of patients with optimal surgical outcome. The aim of the study was to analyze the predictive role of HE4 for surgical outcome and platinum response in EOC patients experiencing a first relapse. Secondary aims were the prognostic role of HE4 for OS and progression-free survival (PFS).

Methods: Plasma was obtained before secondary cytoreduction from 73 EOC patients. A total of 66.7 % underwent a total macroscopic tumor clearance; 86.3 % of the patients had disease that responded to platinum therapy. HE4 was detected by enzyme-linked immunosorbent assay. For statistical analysis, the chi-square test, Fisher's exact test, Kendall's tau b, and Mann-Whitney U test were used. OS, PFS rates, and respective 95 % confidence intervals (CI) were estimated according to the Kaplan-Meier method.

Results: At a HE4 cutoff value of 250 pMk, a sensitivity of 52 % and a specificity of 93.8 % (p = 0.001, 95 % CI 0.601-0.861) were reached in predicting total macroscopic tumor clearance. Plasma HE4 concentrations together with platinum response were the only independent prognostic factors for OS (p < 0.001, hazard ratio [HR] 18.77, 95 % CI 4.68-75.25; and p = 0.044, HR 3.33, 95 % CI 1.03-10.7, respectively). Together with ascites, HE4 was the only independent predictive factor for surgical outcome (p = 0.029, odds ratio [OR] 7.2, 95 % CI 1.22-42.19 and p = 0.036, OR 10.18, 95 % CI 1.16-88.69, respectively).

Conclusions: HE4 is an independent predictive marker for surgical outcome and OS in patients with recurrent EOC. Larger population studies are needed to validate these results.

MeSH terms

  • Adenocarcinoma, Mucinous / blood
  • Adenocarcinoma, Mucinous / mortality*
  • Adenocarcinoma, Mucinous / surgery
  • Adult
  • Aged
  • Cystadenocarcinoma, Serous / blood
  • Cystadenocarcinoma, Serous / mortality*
  • Cystadenocarcinoma, Serous / surgery
  • Endometrial Neoplasms / blood
  • Endometrial Neoplasms / mortality*
  • Endometrial Neoplasms / surgery
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoblotting
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / surgery
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / surgery
  • Prognosis
  • Proteins / metabolism*
  • Survival Rate
  • WAP Four-Disulfide Core Domain Protein 2
  • Young Adult


  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human