Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms: Clinical correlates

Gynecol Oncol. 2015 Jun;137(3):430-5. doi: 10.1016/j.ygyno.2015.03.044. Epub 2015 Apr 9.

Abstract

Objectives: To measure HE4 levels in urine from normal donors, patients with LMP tumors and ovarian cancer patients and to correlate levels with clinical factors in ovarian cancer patients.

Methods: Archived samples from controls, patients with LMP tumors and ovarian cancer were tested using commercial assays, including serially collected serum and urine samples from women treated for stage III/IV serous ovarian cancer.

Results: Five of 6 patients with stage I/II and 26 of 36 stage III/IV serous ovarian cancer patients had HE4-positive urines, similar to serum samples (4 of 5 stage I/II and 26 of 34 stage III/IV) when tested at the same level of specificity (95%). Urine HE4 was more sensitive in LMP tumors: 9 of 32 urines (28%) HE4-positive versus 3 of 68 sera (4.4%, p=0.002). Mean levels of serum CA125 and HE4 decreased comparably in patients during initial treatment regardless of their primary platinum response, but mean urine HE4 levels decreased only 7% in primary platinum resistant patients while decreasing 68% in those who were sensitive. By 7months after diagnosis, urine HE4 levels were higher in primary platinum resistant patients compared to those who proved to be sensitive (p=0.051) and persisted 12months after diagnosis (p=0.014). HE4 values in urine also became positive in advance of clinical recurrence in several women while serum HE4 and serum CA-125 remained normal.

Conclusions: Measuring HE4 in urine complements serum assays for the detection of ovarian cancer and may allow identification of patients at high risk for primary platinum resistance.

Keywords: ELISA; HE4; LMP; Ovarian cancer; Urine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / urine*
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Female
  • Humans
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / urine*
  • Ovarian Neoplasms / urine*
  • Proteins / metabolism*
  • WAP Four-Disulfide Core Domain Protein 2

Substances

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