Human epididymis protein 4 (HE4) and ovarian cancer prognosis

Objective. A cohort study was conducted to evaluate whether preoperative plasma HE4 levels could predict the occurrence of death (primary endpoint) and progression (secondary endpoint) in women with ovarian cancer (OC). Methods. Between 1998 and 2006, we recruited 136 women newly diagnosed with DC of any FIGO stage at the University Hospital, CHUQ-L'Hotel-Dieu de Quebec, Canada. HE4 was measured using the Abbott's ARCHITECT HE4 assay. Dates of death were obtained by record linkage with the Quebec mortality files. Progression was evaluated using the CA-125 or the RECIST criteria, as recommended by the Gynecology Cancer Intergroup. Adjusted hazard ratios (HR) of death and progression, as well as their 95% confidence intervals (Cl), were estimated using the Cox proportional hazard regression model. Results. Preoperative levels of HE4 were strongly associated with all DC standard prognostic factors. HE4 levels increased significantly with age (p=0.02), FIGO stage (p<0.0001), grade (p=0.005), preoperative CA-125 levels (p<0.0001), and residual tumor (p<0.0001). HE4 levels above the median value (394 pmol/L) were significantly associated with mortality (HR=2.17; 95% Cl: 1.42-3.32) and progression (HR=1.81; 95% Cl: 1.21-2.72). After adjustment for the FIGO stage, which was the only factor significantly associated with prognosis in multivariate analyses, the association of HE4 with death remained statistically significant (HR=1.67; 95% Cl: 1.08-2.59). However, the association with progression was no longer significant (HR=1.32; 95% Cl: 0.87-1.99). Conclusion. These results show that preoperative the plasma level of HE4 is a marker of DC aggressiveness and a predictor of death. (C) 2012 Elsevier Inc. All rights reserved.