title: Roles of human epididymis protein 4, carbohydrate antigen 125, inhibin B and anti-Müllerian hormone in the differential diagnosis and follow-up of ovarian granulosa cell tumors.
abstract: OBJECTIVE
  Evaluation of circulating tumor markers in ovarian cancer is crucial for optimal patient care. The goal of this study was to verify the most accurate circulating tumor markers for the diagnosis and follow-up of adult-type granulosa cell tumors (AGCTs).
  
  
  METHODS
  The levels of circulating human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125), together with AGCT markers inhibin B and anti-Müllerian hormone (AMH), were measured in 135 samples from AGCT patients, 37 epithelial ovarian carcinoma (EOC) patients, and 40 endometrioma (ENDO) patients. The levels were plotted with receiver operating characteristic (ROC) graphs, and the area under the curves (AUC) of the different markers were calculated and compared.
  
  
  RESULTS
  HE4 levels were significantly lower in AGCTs than in EOCs (p<0.0001). CA125 levels were above 35IU/l in 25% of AGCT patients and 47.5% of ENDO patients, whereas inhibin B and AMH levels were elevated only in patients with AGCTs. In the AUC comparison analyses, inhibin B alone was sufficient to differentiate AGCT from EOC. In differentiating AGCT from ENDO, inhibin B and AMH performed similarly, and the combination of inhibin B and AMH increased the accuracy compared to either marker alone (sensitivity, 100%; specificity, 93%). Among AGCT patients, inhibin B was the best marker for detecting the presence of AGCT.
  
  
  CONCLUSIONS
  HE4 and CA125 levels were low in AGCTs, and inhibin B was the most accurate circulating biomarker in distinguishing AGCTs from EOCs and from ENDOs. Inhibin B was also the best single marker for AGCT follow-up.
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland.
authors.forename: Ulla-Maija
authors.initials: UM
authors.lastname: Haltia
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20520 Turku, Finland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Hallamaa
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Tapper
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20520 Turku, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hynninen
authors.affiliation: Clinical Chemistry, University of Helsinki and HUSLAB, Finland.
authors.forename: Henrik
authors.initials: H
authors.lastname: Alfthan
authors.affiliation: AnshLabs, Webster, TX, USA.
authors.forename: Bhanu
authors.initials: B
authors.lastname: Kalra
authors.affiliation: Physiology, Faculty of Medicine, University of Helsinki, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Ritvos
authors.affiliation: Children's Hospital, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland; Department of Pediatrics, St. Louis Children´s Hospital, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Markku
authors.initials: M
authors.lastname: Heikinheimo
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland.
authors.forename: Leila
authors.initials: L
authors.lastname: Unkila-Kallio
authors.affiliation: Department of Obstetrics and Gynecology, University of Turku and Turku University Hospital, 20520 Turku, Finland; Department of Physiology, Institute of Biomedicine, University of Turku, 20014 Turku, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Perheentupa
authors.affiliation: Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland; Children's Hospital, University of Helsinki and Helsinki University Hospital, PO Box 20, 00014, University of Helsinki, Finland. Electronic address: Anniina.farkkila@helsinki.fi.
authors.forename: Anniina
authors.initials: A
authors.lastname: Färkkilä
mesh_terms: D000328:Adult; D000359:Aftercare; D000368:Aged; D000369:Aged, 80 and over; D054304:Anti-Mullerian Hormone / Q000097:blood; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D003937:Diagnosis, Differential; D004715:Endometriosis / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006106:Granulosa Cell Tumor / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D007265:Inhibins / Q000097:blood; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis*; D011506:Proteins / Q000378:metabolism; D012372:ROC Curve; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human; C422364:inhibin B; D007265:Inhibins; D054304:Anti-Mullerian Hormone
keywords: AMH; CA125; Granulosa cell tumor; HE4; Inhibin B; Ovarian cancer