title: Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass.
abstract: OBJECTIVE
  Diagnostic factors are needed to improve the currently used serum CA125 and risk of malignancy index (RMI) in differentiating ovarian cancer (OC) from other pelvic masses, thereby achieving precise and fast referral to a tertiary center and correct selection for further diagnostics. The aim was to evaluate serum Human Epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) for these purposes.
  
  
  METHODS
  Serum from 1218 patients in the prospective ongoing pelvic mass study was collected prior to diagnosis. The HE4 and CA125 data were registered and evaluated separately and combined in ROMA and compared to RMI.
  
  
  RESULTS
  809 benign tumors, 79 borderline ovarian tumors, 252 OC (64 early and 188 late stage), 9 non-epithelial ovarian tumors and 69 non-ovarian cancers were evaluated. Differentiating between OC and benign disease the specificity was 62.2 (CA125), 63.2 (HE4), 76.5 (ROMA) and 81.5 (RMI) at a set sensitivity of 94.4 which corresponds to RMI=200. The areas under the curve (AUC) were 0.854 (CA125), 0.864 (HE4), 0,897 (ROMA) and 0.905 (RMI) for benign vs. early stage OC. For premenopausal benign vs. OC AUC were 0.925 (CA125), 0.905 (HE4), 0.909 (ROMA) and 0.945 (RMI).
  
  
  CONCLUSIONS
  HE4 and ROMA helps differentiating OC from other pelvic masses, even in early stage OC. ROMA performs equally well as the ultrasound depending RMI and might be valuable as a first line biomarker for selecting high risk patients for referral to a tertiary center and further diagnostics. Further improvements of HE4 and ROMA in differentiating pelvic masses are still needed, especially regarding premenopausal women.
authors: Department of Pathology, Molecular Unit, Herlev University Hospital, University of Copenhagen, Denmark.
authors: Mona Aarenstrup
authors: MA
authors: Karlsen
authors: Noreen
authors: N
authors: Sandhu
authors: Claus
authors: C
authors: Høgdall
authors: Ib Jarle
authors: IJ
authors: Christensen
authors: Lotte
authors: L
authors: Nedergaard
authors: Lene
authors: L
authors: Lundvall
authors: Svend A
authors: SA
authors: Engelholm
authors: Anette T
authors: AT
authors: Pedersen
authors: Dorthe
authors: D
authors: Hartwell
authors: Magnus
authors: M
authors: Lydolph
authors: Inga Alice
authors: IA
authors: Laursen
authors: Estrid V S
authors: EV
authors: Høgdall
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D003661:Decision Support Techniques; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000175:diagnosis*; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D010386:Pelvic Neoplasms / Q000097:blood / Q000175:diagnosis*; D011446:Prospective Studies; D011506:Proteins / Q000378:metabolism*; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D000081102:WAP Four-Disulfide Core Domain Protein 2; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human