title: Clinical value of human epididymis protein 4 and the Risk of Ovarian Malignancy Algorithm in differentiating borderline pelvic tumors from epithelial ovarian cancer in early stages.
abstract: OBJECTIVE
  The clinical value of human epididymis protein 4 (HE4) and the possibility of its use in the differential diagnosis in patients with benign, borderline and epithelial ovarian cancer in early International Federation of Gynaecology and Obstetrics (FIGO) stages.
  
  
  METHODS
  The study group consisted of 205 women, including 60 with ovarian cancer, 18 with borderline tumors, 77 with benign lesions and 50 healthy subjects. In all the patients, before the treatment and in control groups, we determined CA 125 and HE4 in serum by electrochemiluminescence on the basis of the COBAS e601 system. For comparison of two independent groups, we used the U Mann-Whitney test. The analysis of the diagnostic power of the assessed parameters has been determined using the MedCalc statistical program. The probability of disease free survival (DFS) was evaluated using the log-rank test and Cox regression model.
  
  
  RESULTS
  Concentrations of HE4, CA 125 and Risk of Ovarian Malignancy Algorithm (ROMA) value were significantly higher in early ovarian cancer than in patients with benign (P<0.0001) and borderline tumors (P<0.002), the receiver operating characteristics (ROC) curves, demonstrated the highest diagnostic sensitivity for the ROMA score, as well post (AUC=0.817) as pre-menopausal (AUC=0.806). HE4 concentrations (P<0.021) and the value of the ROMA score (P<0.004) were significantly higher in patients with relapse than in patients in remission. There was no connection between concentrations of the studied tumor markers and DFS.
  
  
  CONCLUSIONS
  Determination of HE4 serum concentrations has a significant clinical value, especially in patients with benign lesions and elevated CA 125 levels. The combined assessment of HE4, CA 125 and the ROMA algorithm is helpful in differentiating benign tumors and borderline pelvic tumors from epithelial ovarian cancer in early FIGO stages. Determination of HE4, CA 125 and ROMA algorithm is not helpful in differentiating patients with borderline from benign lesions.
authors.affiliation: The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Laboratory of Tumor Markers, Department of Pathology and Laboratory Diagnostics, Roentgen Street 5, 02-781 Warsaw, Poland. Electronic address: bkotowicz@coi.pl.
authors.forename: Beata
authors.initials: B
authors.lastname: Kotowicz
authors.affiliation: The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Laboratory of Tumor Markers, Department of Pathology and Laboratory Diagnostics, Roentgen Street 5, 02-781 Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Fuksiewicz
authors.affiliation: The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Department of Gynecologic Oncology, Roentgen Street 5, 02-781 Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Sobiczewski
authors.affiliation: The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Department of Gynecologic Oncology, Roentgen Street 5, 02-781 Warsaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Spiewankiewicz
authors.affiliation: The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Department of Urooncology, Roentgen Street 5, 02-781 Warsaw, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jonska-Gmyrek
authors.affiliation: Second Department of Gynecology, Prof. F. Skubiszewski University School of Medicine, Lublin, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Skrzypczak
authors.affiliation: The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Laboratory of Tumor Markers, Department of Pathology and Laboratory Diagnostics, Roentgen Street 5, 02-781 Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Kowalska
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D062625:Cystadenofibroma / Q000097:blood* / Q000473:pathology*; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000473:pathology*; D016016:Proportional Hazards Models; D011506:Proteins / Q000378:metabolism*; D012372:ROC Curve; D012307:Risk Factors; 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
keywords: Borderline tumors; Human epididymis protein 4; Ovarian cancer; Prognostic factors