title: The diagnostic accuracy of two human epididymis protein 4 (HE4) testing systems in combination with CA125 in the differential diagnosis of ovarian masses.
abstract: BACKGROUND
  Cancer antigen 125 (CA125) is the best known single tumor marker for ovarian cancer (OC). We investigated whether the additional information of the human epididymis protein 4 (HE4) improves diagnostic accuracy.
  
  
  METHODS
  We retrospectively analyzed preoperative sera of 109 healthy women, 285 patients with benign ovarian masses (cystadenoma: n=78, leimyoma: n=66, endometriosis: n=52, functional ovarian cysts: n=79, other: n=10), 16 low malignant potential (LMP) ovarian tumors and 125 OC (stage I: 22, II: 15, III: 78, IV: 10). CA125 was analyzed using the ARCHITECT system, HE4 using the ARCHITECT(a) system and EIA(e) technology additionally.
  
  
  RESULTS
  The lowest concentrations of CA125 and HE4 were observed in healthy individuals, followed by patients with benign adnexal masses and patients with LMP tumors and OC. The area under the curve (AUC) for the differential diagnosis of adnexal masses of CA125 alone was not significantly different to HE4 alone in premenopausal (CA125: 86.7, HE4(a): 82.6, HE4(e): 81.6% p>0.05) but significantly different in postmenopausal [CA125: 93.4 vs. HE4(a): 88.3 p=0.023 and vs. HE4(e): 87.8% p=0.012] patients. For stage I OC, HE4 as a single marker was superior to CA125, which was the best single marker in stage II-IV. The combination of CA125 and HE4 using risk of malignancy algorithm (ROMA) gained the highest sensitivity at 95% specificity for the differential diagnosis of adnexal masses [CA125: 70.9, HE4(a): 67.4, HE4(e): 66.0, ROMA(a): 76.6 and ROMA(e): 74.5%], especially in stage I OC [CA125: 27.3, HE4(a): 40.9, HE4(e): 40.9, ROMA(a): 45.5 and ROMA(e): 45.5%].
  
  
  CONCLUSIONS
  CA125 is still the best single marker in the diagnosis of OC. HE4 alone and even more the combined analysis of CA125 and HE4 using ROMA improve the diagnostic accuracy of adnexal masses, especially in early OC.
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig- Maximilians-University Munich, Grosshadern Campus, Munich, Germany. Miriam.Lenhard@med.uni-muenchen.de
authors.forename: Miriam
authors.initials: M
authors.lastname: Lenhard
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
authors.forename: Linda
authors.initials: L
authors.lastname: Hertlein
authors.forename: Angela
authors.initials: A
authors.lastname: Kirschenhofer
authors.forename: Sophie
authors.initials: S
authors.lastname: Fürst
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.forename: Karin
authors.initials: K
authors.lastname: Hofmann
authors.forename: Katja
authors.initials: K
authors.lastname: Krocker
authors.forename: Alexander
authors.initials: A
authors.lastname: Burges
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*; D003937:Diagnosis, Differential; D030501:Epididymal Secretory Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007118:Immunoassay; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis*; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D030501:Epididymal Secretory Proteins