Elecsys® HE4 - Human epididymal protein 4

Improving care for ovarian cancer patients

  • Human epididymal protein 4 (HE4) is a biomarker that is highly elevated in epithelial ovarian cancer and has been shown to be involved in ovarian cancer cell proliferation and invasion1-3
  • HE4 increases the sensitivity of CA125 in the detection of ovarian cancer in patients presenting with pelvic mass4
  • Among women presenting with pelvic mass, the combined use of HE4 and CA 125 using ROMA (Risk of Ovarian Malignancy Algorithm) can increase the sensitivity and specificity of detecting ovarian cancer - even stages I/II ovarian cancer – than CA 125 alone5-7
  • In addition, HE4 complements CA 125 in identifying patients with disease recurrence and disease progression8-10



ROMA algorithm
Elecsys® HE4 - Human epididymal protein 4

Risk of Ovarian Malignancy Algorithm (ROMA) with Elecsys HE4 and CA 125

Accurate stratification of women with stage I-IV ovarian cancer:

83.3% were correctly classified as high risk
75.6% were correctly classifed as low risk
Positive predictive value of 65%
Negative predictive value of 90%

Elecsys HE4
Assay time
18 min.
Sample material Serum collected using standard sampling tubes or tubes containing separating gel
Li-heparin plasma, K2-EDTA and K3-EDTA plasma
Sample volume 10 µL
Detection Limit* LoD 15 pmol/L
Measuring Range 15 - 1,500 pmol/L
Intermediate precision cobas e 411, Elecsys 2010 analyzer: 2.7 - 4.3 %
cobas e 601/e 602 modules E170: 2.6 - 3.4 %
Traceablity HE4 EIA from Fujirebio Diagnostics

*LoD = Limit of Detection

Clinical benefit #1: Among women presenting with pelvic mass, a combined use of HE4 and CA 125 using ROMA (Risk of Ovarian Malignancy Algorithm) can increase the sensitivity and specificity of detecting ovarian cancer - even stages I/II ovarian cancer – as compared to testing CA 125 alone

  • ROMA accurately identifies 94% of the patients with pelvic mass as having ovarian cancer5
  • ROMA has a higher sensitivity than CA 125 alone: Among ten women with ovarian cancer, ROMA identifies one more patient than CA 125 alone (sensitivity: ROMA 90% vs. CA 125 79%)6
  • ROMA has a higher specificity than CA 125 alone: Among ten women with benign gynecologic diseases, ROMA dismisses one more patient which CA125 alone would include as having ovarian cancer (Specificity: ROMA 93% vs. CA 125 86%)6
  • ROMA has a higher sensitivity and specificity in detecting stages I/II ovarian cancer than CA 125 alone7

Clinical benefit #2: HE4 and CA 125 together improve ovarian cancer monitoring

  • Either HE4 or CA 125 levels can be elevated in patients during therapy monitoring and recurrence monitoring 8-10
  • At disease progression, some patients show an elevated HE4 level earlier than an increase in CA 125 level, and others show an elevated CA 125 level earlier than an increase in HE4 level. Therefore, HE4 and CA 125 together can effectively monitor therapy response8-10
  • As patients with elevated CA 125 level at diagnosis can switch to elevated HE4 level at follow up, and vice versa, testing for both HE4 and CA 125 can identify patients with recurrent disease that CA 125 alone would miss10

Technical benefit: Efficiency and reliability for the laboratory

  • Elecsys® HE4 
    • Shows excellent precision across the entire measuring range for reliable results
    • Has 28 days of stability at 2-8˚C after opening
    • Is fast with 18 minute assay time
    • Is available for use inboth serum and plasma
  • Consolidation of 17 tumor marker assays is available on one automated platform

References

1. Moore, R.G. et al. (2012) Scientific Reports 4: 3574
2.Lu, R. et al. (2012) Biochem. Biophys. Res. Comm. 419: 274-280
3. Zhu, Y.-F. et al. (2013) Asian Pacific Journal of Tropical Medicine. 265-272
4. Moore, R.G. et al. (2008). Gynecol Oncol. 108, 402–408
5. Moore, R.G. et al. (2011) Obstet. Gynecol. 118: 280-288
6. Ortiz-Muñoz, B. et al. (2012) Tumor Biol. 35(7): 7249-58
7. Karlsen, M.A. et al. (2012). Gynecol Oncol. 127: 379-383
8. Schummer, M. et al. (2012) Gynecol. Oncol. 125: 65–69 
9. 
Allard, J. et al. (2008) J Clin Oncol. 26 (May 20 Suppl): abstract 5535 
10. 
Escudero, J.M. et al. (2014). Tumor Biol. 35 (Suppl 1): S1-S9