title: Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms: Clinical correlates.
abstract: OBJECTIVE
  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.
authors: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: John B
authors: JB
authors: Liao
authors: Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Yuen Yee
authors: YY
authors: Yip
authors: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Elizabeth M
authors: EM
authors: Swisher
authors: Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Kathy
authors: K
authors: Agnew
authors: Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors: Karl Erik
authors: KE
authors: Hellstrom
authors: Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: ihellstr@u.washington.edu.
authors: Ingegerd
authors: I
authors: Hellstrom
mesh_terms: D014408:Biomarkers, Tumor / Q000652:urine*; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000652:urine*; D010051:Ovarian Neoplasms / Q000652:urine*; D011506:Proteins / Q000378:metabolism*; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: ELISA; HE4; LMP; Ovarian cancer; Urine