title: HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) as diagnostic tools for ovarian cancer in patients with a pelvic mass: An Italian multicenter study.
abstract: OBJECTIVE
  This multicenter study aims to evaluate HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) performance in the differential diagnosis of epithelial ovarian cancer (EOC).
  
  
  METHODS
  A total of 405 patients referred to gynecological oncologist with suspicious pelvic mass requiring a surgery for identification of EOC were consecutively enrolled; 387 patients satisfied inclusion criteria: 290 benign diseases; 15 borderline neoplasia and 82 tumors (73 EOC).
  
  
  RESULTS
  Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125, HE4 and ROMA when calculating optimal cut-off values: premenopause, specificity (SP) >86.6, sensitivity (SN) >82.6, area under the curves (AUC)≥0.894; postmenopause, SP>93.2, SN>82, AUC≥0.928. Fixing SP at 98%, performance indicators obtained for benign vs EOC patients were: premenopause, SN:65.2%, positive predictive value (+PV): 75%, positive likelihood ratio (+LR): 26.4 for CA125; SN:69.6%, +PV:76.2%, +LR:28.1 for HE4; SN:69.6%, +PV: 80%; +LR:35.1 for ROMA; postmenopause, SN:88%, +PV: 95.7%, +LR:38.7 for CA125; SN:78%, +PV:95.1%, +LR:34.3 for HE4; SN:88%, +PV:97.8%, +LR:77.4 for ROMA. When using routine cut-off thresholds, ROMA showed better well-balanced values of both SP and SN (premenopause, SN:87%, SP:86.1%; postmenopause, SN:90%; SP:94.3%).
  
  
  CONCLUSIONS
  Overall, ROMA showed well balanced diagnostic performance to differentiate EOC from benign diseases. Meaningful differences of +PVs and +LRs between HE4 and CA125 suggest that the two markers may play at least in part different roles in EOC diagnosis, with HE4 seeming to be more efficient than CA125 in ruling in EOC patients in the disease group, also in early stages tumors, both in pre and postmenopause.
authors.affiliation: Unit of Gynecology and Obstetrics, G. Fracastoro Hospital, Via Circonvallazione 1, 37047 San Bonifacio, Verona (VR), Italy. Electronic address: cromagnolo@ulss20.verona.it.
authors.forename: Cesare
authors.initials: C
authors.lastname: Romagnolo
authors.affiliation: Regional Center for Biomarkers, Department of Clinical Pathology, Azienda ULSS12 Veneziana, Regional Hospital, Campo SS Giovanni e Paolo 6777, 30122 Venice (VE), Italy. Electronic address: antonette.leon@ulss12.ve.it.
authors.forename: Antonette E
authors.initials: AE
authors.lastname: Leon
authors.affiliation: Experimental and Clinical Pharmacology Unit, CRO Aviano National Cancer Institute, IRCCS, Via Franco Gallini 2, 33081 Aviano (PN), Italy; Regional Center for Biomarkers, Department of Clinical Pathology, Azienda ULSS12 Veneziana, Regional Hospital, Campo SS Giovanni e Paolo 6777, 30122 Venice (VE), Italy. Electronic address: aline.fabricio@ulss12.ve.it.
authors.forename: Aline S C
authors.initials: ASC
authors.lastname: Fabricio
authors.affiliation: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: mtaborelli@cro.it.
authors.forename: Martina
authors.initials: M
authors.lastname: Taborelli
authors.affiliation: Unit of Epidemiology and Biostatistics, CRO Aviano National Cancer Institute, IRCCS, via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: polesel@cro.it.
authors.forename: Jerry
authors.initials: J
authors.lastname: Polesel
authors.affiliation: Division of Gynecological Oncology, CRO Aviano National Cancer Institute, IRCCS, Via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: ldelpup@cro.it.
authors.forename: Lino
authors.initials: L
authors.lastname: Del Pup
authors.affiliation: CRO-Biobank, Clinical Cancer Pathology, CRO Aviano National Cancer Institute, IRCCS, Via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: asteffan@cro.it.
authors.forename: Agostino
authors.initials: A
authors.lastname: Steffan
authors.affiliation: CRO-Biobank, Clinical Cancer Pathology, CRO Aviano National Cancer Institute, IRCCS, Via Franco Gallini 2, 33081 Aviano (PN), Italy. Electronic address: scervo@cro.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Cervo
authors.affiliation: Division of Gynecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Spedali Civili 1, 25123 Brescia, (BS), Italy. Electronic address: antonella.ravaggi@unibs.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Ravaggi
authors.affiliation: Division of Gynecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Spedali Civili 1, 25123 Brescia, (BS), Italy. Electronic address: laura.zanotti84@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Zanotti
authors.affiliation: Division of Gynecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Spedali Civili 1, 25123 Brescia, (BS), Italy. Electronic address: bandieraelisabetta@libero.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bandiera
authors.affiliation: Division of Gynecologic Oncology, "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia, Spedali Civili 1, 25123 Brescia, (BS), Italy. Electronic address: odicino.franco@gmail.com.
authors.forename: Franco E
authors.initials: FE
authors.lastname: Odicino
authors.affiliation: Department of Clinical Pathology, G. Fracastoro Hospital, Via Circonvallazione 1, 37047 San Bonifacio, Verona (VR), Italy. Electronic address: novella.scattolo@ulss20.verona.it.
authors.forename: Novella
authors.initials: N
authors.lastname: Scattolo
authors.affiliation: Istituto Oncologico Veneto (IOV), IRCCS, Via Gattamelata, 64, 35128 Padova (PD), Italy. Electronic address: elisa.squarcina@libero.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Squarcina
authors.affiliation: Unit of Obstetrics and Gynecology, Dell'Angelo Hospital, Via Paccagnella 11, 30174 Mestre (VE), Italy. Electronic address: christine.papadakis@ulss12.ve.it.
authors.forename: Christine
authors.initials: C
authors.lastname: Papadakis
authors.affiliation: Unit of Obstetrics and Gynecology, Dell'Angelo Hospital, Via Paccagnella 11, 30174 Mestre (VE), Italy. Electronic address: tiziano.maggino@ulss12.ve.it.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Maggino
authors.affiliation: Regional Center for Biomarkers, Department of Clinical Pathology, Azienda ULSS12 Veneziana, Regional Hospital, Campo SS Giovanni e Paolo 6777, 30122 Venice (VE), Italy. Electronic address: massimo.gion@ulss12.ve.it.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gion
mesh_terms: D000328:Adult; D000465:Algorithms; D018394:CA-125 Antigen / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007118:Immunoassay; D008565:Membrane Proteins / Q000097:blood*; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D011506:Proteins / Q000378:metabolism*; D012307:Risk Factors; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: 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: CA125; Epithelial ovarian cancer; HE4; Pelvic mass; ROMA; Tumor markers