title: Comparison of serum human epididymis protein 4 with cancer antigen 125 as a tumor marker in patients with malignant and nonmalignant diseases.
abstract: BACKGROUND
  Human epididymis protein 4 (HE4), a precursor of human epididymis protein, has been proposed as a tumor marker for ovarian cancer. We evaluated HE4 in comparison with cancer antigen 125 (CA 125) in healthy individuals and in patients with benign and malignant diseases.
  
  
  METHODS
  CA 125 and HE4 serum concentrations were determined in 101 healthy individuals, 535 patients with benign pathologies (292 with benign gynecologic diseases) and 423 patients with malignant diseases (127 with ovarian cancers). CA 125 and HE4 cutoffs were 35 kU/L and 140 pmol/L, respectively.
  
  
  RESULTS
  HE4 and CA 125 results were abnormal in 1.1% and 9.9% of healthy individuals and in 12.3% and 37% of patients with benign diseases, respectively. Renal failure was the most common cause of increased HE4 in patients with benign disease, who had significantly higher HE4 concentrations (P = 0.001) than patients with other benign diseases. HE4 showed a higher specificity than CA 125 in patients with benign gynecologic diseases, with abnormal concentrations in 1.3% and 33.2% of the patients, respectively. HE-4 concentrations were abnormal primarily in gynecologic cancer and lung cancer. By contrast, CA 125 was increased in many different nonovarian malignancies, including nonepithelial tumors. A significantly higher area under the ROC curve was obtained with HE4 than with CA 125 for differentiating benign from malignant diseases (0.755 vs 0.643) and in the differential diagnosis of gynecologic diseases (0.874 vs 0.722).
  
  
  CONCLUSIONS
  HE4 has significantly higher diagnostic specificity than CA 125, and the combination of CA 125 and HE4 improved the detection of ovarian cancer in all stages and histological types.
authors.affiliation: Laboratory of Clinical Biochemistry (Unit for Cancer Research), Medical School, Barcelona, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Escudero
authors.forename: Jose M
authors.initials: JM
authors.lastname: Auge
authors.forename: Xavier
authors.initials: X
authors.lastname: Filella
authors.forename: Aureli
authors.initials: A
authors.lastname: Torne
authors.forename: Jaume
authors.initials: J
authors.lastname: Pahisa
authors.forename: Rafael
authors.initials: R
authors.lastname: Molina
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D003937:Diagnosis, Differential; D030501:Epididymal Secretory Proteins / Q000378:metabolism*; D005260:Female; D005833:Genital Neoplasms, Female / Q000097:blood / Q000175:diagnosis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D017698:Postmenopause; D017697:Premenopause; D012372:ROC Curve; D012016:Reference Values; D012680:Sensitivity and Specificity; D012737:Sex Factors; D055815:Young Adult; D023083:beta-Defensins
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C426184:DEFB126 protein, human; D030501:Epididymal Secretory Proteins; D023083:beta-Defensins