title: Diagnostic performance and establishment of reference limits of HE4 in Korean healthy women.
abstract: We aimed to establish distribution and reference limits of HE4 and risk of ovarian malignancy algorithm (ROMA) in healthy Korean women and investigated the factors influencing HE4 levels. We also investigated the diagnostic performances of HE4 and ROMA score, compared with CA125.
  
  
  
  We collected specimens from 1809 healthy Korean women, 140 specimens from patients with ovarian cancers (OCs) and 123 specimens from patients with benign ovarian tumor. Serum HE4 and CA125 concentrations were measured using an electrochemiluminescence immunoassay. The receiver operator characteristic (ROC) curve analysis was done for ROMA, HE4, CA125 and combining of HE4 and CA125.
  
  
  
  HE4 level was influenced by age, not by menopausal status. The 97.5th percentile upper reference limit of HE4 of subjects <50years and ≥50year-old was 63.87pmol/L and 88.28pmol/L, respectively. The 97.5th percentile upper reference limits of ROMA score were 13.66 in premenopausal and 19.30 in postmenopausal women. The serum HE4 level was even lower in the patients with benign tumor compared to those in healthy controls. HE4 had significantly higher concentrations in OCs than benign ovarian tumor (P<0.001). ROMA and HE4 combined with CA125 or not performed better diagnostically than CA125 alone for distinguishing OCs, with AUCs of 0.844 for ROMA, 0.827 for combining of HE4 and CA125, 0.825 for HE4, and 0.795 for CA125.
  
  
  
  The reference limit of HE4 was different from those reported by other studies, suggesting racial or regional difference. HE4 and ROMA were better than CA125 for differentiation normal and benign ovarian tumor from OCs. (Word count: 253).
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Shinae
authors.initials: S
authors.lastname: Yu
authors.affiliation: KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hyosoon
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Biostatistics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Mi Yeon
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Occupational and Environmental Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Seungho
authors.initials: S
authors.lastname: Ryu
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: mjkkmd@gmail.com.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.affiliation: Department of Laboratory Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: drwhy@hanmail.net.
authors.forename: Hee-Yeon
authors.initials: HY
authors.lastname: Woo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D018394:CA-125 Antigen / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D011506:Proteins / Q000032:analysis*; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: Benign ovarian tumor; CA125; Human epididymis protein 4; Ovarian cancer; Risk of ovarian malignancy algorithm