Serum human epididymis protein 4 and risk for ovarian malignancy algorithm as new diagnostic and prognostic tools for epithelial ovarian cancer management.
BACKGROUND
The aim of this work was to analyze the diagnostic and prognostic value of serum human epididymis protein 4 (HE4) and Risk for Ovarian Malignancy Algorithm (ROMA) in epithelial ovarian cancer (EOC).


METHODS
Preoperative serum samples of 419 women (140 healthy controls, 131 ovarian benign cysts, 34 endometriosis, and 114 EOC) were tested for CA125 and HE4 using fully automated methods (Abbott ARCHITECT) and validated cutoff values.


RESULTS
For the discrimination of benign masses from EOC, in premenopausal women, the sensitivity and specificity were 92.3% and 59.4% for CA125, 84.6% and 94.2% for HE4, and 84.6% and 81.2% for ROMA, whereas in postmenopausal women, the sensitivity and specificity were 94.3% and 82.3% for CA125, 78.2% and 99.0% for HE4, and 93.1% and 84.4% for ROMA. In patients with EOC, elevated CA125, HE4, and ROMA levels were associated with advanced Federation of Gynaecologists and Obstetricians (FIGO) stage, suboptimally debulking, ascites, positive cytology, lymph node involvement, and advanced age (all P ≤ 0.05). Elevated HE4 and ROMA (both P ≤ 0.01), but not CA125 (P = 0.0579), were associated with undifferentiated tumors. In multivariable analysis, elevated HE4 and ROMA (all P ≤ 0.05) were independent prognostic factors for shorter overall, disease-free, and progression-free survival.


CONCLUSIONS
This study underlines the high specificity of HE4 in discriminating endometriosis and ovarian benign cysts from EOC and the high sensitivity of CA125 in detecting EOC. We showed HE4 and ROMA as independent prognostic factors. Multicenter studies are needed to draw firm conclusions about the applicability of HE4 and ROMA in clinical practice.
Angelo Nocivelli, Institute of Molecular Medicine, Division of Gynecologic Oncology, University of Brescia, Brescia, Italy. bandieraelisabetta@libero.it
Elisabetta
E
Bandiera
Chiara
C
Romani
Claudia
C
Specchia
Laura
L
Zanotti
Claudio
C
Galli
Giuseppina
G
Ruggeri
Germana
G
Tognon
Eliana
E
Bignotti
Renata A
RA
Tassi
Franco
F
Odicino
Luigi
L
Caimi
Enrico
E
Sartori
Alessandro D
AD
Santin
Sergio
S
Pecorelli
Antonella
A
Ravaggi
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis; D011379:Prognosis; D011506:Proteins / Q000032:analysis*; D012307:Risk Factors; D000081102:WAP Four-Disulfide Core Domain Protein 2; D055815:Young Adult
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human