title: Anti-HE4 antibodies in infertile women and women with ovarian cancer.
abstract: OBJECTIVE
  To develop an assay for anti-HE4 antibodies and assess such antibodies in sera from women with increased epidemiologic risk for ovarian cancer (infertility) and patients with ovarian cancer in comparison to controls.
  
  
  METHODS
  An ELISA was developed to measure antibodies to recombinant full length HE4 and cut-off values were determined for different levels of specificity (up to 99%).
  
  
  RESULTS
  Infertile women more frequently had anti-HE4 antibodies than controls (23% at 98% specificity, p < 0.001) with antibodies most frequent in women with POF (31%) and ovulatory dysfunction (47%). There was also an increased frequency of anti-HE4 antibodies in patients with ovarian cancer (14% at 97% specificity, p < 0.01), but more women with certain types of infertility have anti-HE4 antibodies than women with ovarian cancer. Most patients with ovarian cancer have circulating HE4 antigen, which may interfere with detection of antibodies, while the level of HE4 antigen in sera from infertile women was not higher than in normal controls. There was a statistically significant correlation between antibodies to HE4 and antibodies to mesothelin in the same patients.
  
  
  CONCLUSIONS
  Women with certain types of infertility, which have increased risk to develop ovarian cancer, and women with ovarian cancer more frequently than controls have antibodies to HE4, a biomarker for ovarian cancer. The antibodies may reflect a tumor-promoting Th2 type of inflammation.
authors.affiliation: Department of Pathology, Harborview Medical Center, Seattle, WA 98104, United States. ihellstr@u.washington.edu
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Hellstrom
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Swisher
authors.forename: Karl Erik
authors.initials: KE
authors.lastname: Hellstrom
authors.forename: Yuen Yee
authors.initials: YY
authors.lastname: Yip
authors.forename: Kathy
authors.initials: K
authors.lastname: Agnew
authors.forename: Judith L
authors.initials: JL
authors.lastname: Luborsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D000941:Antigens / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D004715:Endometriosis / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D007247:Infertility, Female / Q000276:immunology*; D000090204:Mesothelin; D010051:Ovarian Neoplasms / Q000276:immunology*; D010060:Ovulation / Q000276:immunology; D016649:Primary Ovarian Insufficiency / Q000276:immunology; D011506:Proteins / Q000276:immunology*; D000081102:WAP Four-Disulfide Core Domain Protein 2; D055815:Young Adult
chemical_list: D000906:Antibodies; D000941:Antigens; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; D000090204:Mesothelin
keywords: Cancer diagnostics; Inflammation; Tumor antigens