title: Diagnostic performance of the biomarkers HE4 and CA125 in type I and type II epithelial ovarian cancer.
abstract: OBJECTIVE
  To evaluate the diagnostic performance of HE4 and CA125 in patients presenting with suspicious malignant ovarian cysts. We especially wanted to investigate the levels of HE4 and CA125 with regard to the gene and histology-unifying model of type I and type II epithelial ovarian cancer (EOC).
  
  
  METHODS
  Plasma from 373 women presenting with a suspicious malignant ovarian cyst was collected prior to surgery. Histology, grade, and stage were determined according to FIGO-classification. HE4 and CA125 were analyzed using ELISA, and the markers were evaluated for significance separately and in combination. Receiver operating curves, the area under the curve, sensitivity and specificity were estimated.
  
  
  RESULTS
  The combination of HE4 and CA125 resulted in the best diagnostic power in comparing benign tumors to EOC (ROC AUC 0.93, sensitivity 94.4% at 75% specificity) for type II. Diagnostic power in type I (ROC AUC 0.79, sensitivity 61.9% at 75% specificity) was less impressive. In particular, mucinous benign vs. malignant tumors could not significantly be separated by the dual marker combination. Impressively high ROC AUC 0.99 was found for the late stage type II EOC with 100% sensitivity at 75% specificity.
  
  
  CONCLUSIONS
  HE4 and CA125 have a good ability to diagnose the more aggressive type II tumors but a poor diagnostic ability when patients are presenting with slow-growing type I in the early stage. Our results support the hypothesis that EOC should be looked upon as several different diseases, and that we lack biomarkers for sub-groups of EOC.
authors.affiliation: University of Gothenburg, Institute of Clinical Sciences, Department of Obstetrics and Gynecology, S-41345 Gothenburg, Sweden. Electronic address: bjorg.kristjansdottir@vgregion.se.
authors.forename: Björg
authors.initials: B
authors.lastname: Kristjansdottir
authors.forename: Kristina
authors.initials: K
authors.lastname: Levan
authors.forename: Karolina
authors.initials: K
authors.lastname: Partheen
authors.forename: Karin
authors.initials: K
authors.lastname: Sundfeldt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D010048:Ovarian Cysts / Q000097:blood* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D011506:Proteins / Q000032:analysis*; D012372:ROC Curve; D000081102:WAP Four-Disulfide Core Domain Protein 2; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: CA125; Diagnostic biomarkers; Epithelial ovarian cancer; HE4; Type I and type II EOC