title: HE4 and epithelial ovarian cancer: comparison and clinical evaluation of two immunoassays and a combination algorithm.
abstract: BACKGROUND
  Two commercial immunoassays for HE4 have been compared and the diagnostic accuracy of HE4, CA 125 and the combinatory ROMA algorithm for epithelial ovarian cancer (EOC) has been evaluated.
  
  
  METHODS
  HE4 and CA125 were measured on sera obtained from 259 women (73 healthy, 90 with benign ovarian or adnexal diseases, 96 with EOC). The ARCHITECT CMIA HE4 assay was compared with the Fujirebio EIA HE4, and the risk for EOC by the combinatory ROMA algorithm (HE4+CA 125) was assessed with both HE4 assays.
  
  
  RESULTS
  The CMIA HE4 assay showed a good linearity (r>0.9998) and precision (interassay and total CVs <4%). The correlation with EIA HE4 was linear (r=0.994), with an average bias of 0.4%. By ROC curve analysis, the sensitivity for EOC at a fixed specificity of 90%, 95% and 99% was 89.6%, 84.4% and 79.2% by CMIA HE4, 84.4%, 83.3% and 79.2% by EIA HE4, 86.5%, 76.0% and 59.4% by CMIA CA125. The accuracy of the ROMA algorithm determined by CMIA or EIA HE4 was very similar (AUC 87.1% vs. 87.6%; p=n.s.) and greater in menopause.
  
  
  CONCLUSIONS
  The two HE4 assays showed a good correlation and similar clinical value, with a greater precision for CMIA. HE4 was more specific and accurate than CA125, supporting its use in addition to clinical and imaging criteria for the discrimination of benign from malignant ovarian lesions. The ROMA algorithm showed a good accuracy for discriminating women at high risk for EOC.
authors.affiliation: Department of Laboratory Medicine, A.O. Spedali Civili, Brescia, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Ruggeri
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bandiera
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.forename: Silvana
authors.initials: S
authors.lastname: Belloli
authors.forename: Antonella
authors.initials: A
authors.lastname: Ravaggi
authors.forename: Chiara
authors.initials: C
authors.lastname: Romani
authors.forename: Eliana
authors.initials: E
authors.lastname: Bignotti
authors.forename: Renata A
authors.initials: RA
authors.lastname: Tassi
authors.forename: Germana
authors.initials: G
authors.lastname: Tognon
authors.forename: Claudio
authors.initials: C
authors.lastname: Galli
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.forename: Sergio
authors.initials: S
authors.lastname: Pecorelli
mesh_terms: D000465:Algorithms; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D019411:Clinical Laboratory Techniques; D030501:Epididymal Secretory Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood*; D010051:Ovarian Neoplasms / Q000097:blood*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D023083:beta-Defensins
chemical_list: D018394:CA-125 Antigen; C426184:DEFB126 protein, human; D030501:Epididymal Secretory Proteins; C451759:MUC16 protein, human; D008565:Membrane Proteins; D023083:beta-Defensins