Prognostic significance of serum HE4 in epithelial ovarian cancer.

Abstract

5081 Background: Human epididymis protein 4 (HE4), a relatively new marker for ovarian carcinoma, is the product of the WFDC2 (HE4) gene that is overexpressed in patients with ovarian carcinoma. Using an immunoassay, a small study indicated comparable sensitivity for CA 125 and HE4 in postmenopausal women with ovarian cancer. A subsequent and larger study confirmed the sensitivity of HE4. We investigated the possibility of HE4 to predict survival for patients with EOC. Methods: In the present study we measured serum concentration of HE4 in 35 patients with surgically diagnosed EOC since December 2008 until May 2010. All patients received the same standard of care using an integrative model combining surgery, and chemotherapy as appropriate. Of 35 pts. 28 had stage III disease at diagnosis, and 7 stage IV. Blood samples were obtained before surgery, at each IV chemotherapy cycle and every 3 months. The Kaplan-Meier or product-limit method was used to calculate survival.Serum levels of HE4 were determined using assays and kits developed by Fujirebio Diagnostic, Inc. and were performed according to the manufacturer's specifications. Results: At the time of this analysis (December 2010), 7 patients had expired and 18 were censored. The median age at presentation was 54.2 years (range 38.1 - 73.5 years). At baseline (study entry) no patients had low serum HE4 levels (<100 pM). After 3 cycles of planned chemotherapy, 20 pts had lower serum HE4 levels (<100pM) and 15 had high serum HE4 levels (>100pM); at the end of 6 planned cycles 28 pts had lower serum HE4 levels (<100pM) and 7 had yet high serum HE4 levels (>100pM). All pts with a HE4 plasma level > 400pM at the end of the planned treatment died before December 2010. Patients with a reduced HE4 at both baseline and 3 months had the best overall survival. Conclusions: Our data show that HE4 can improve the monitoring of treatment response and disease progression. Reduction in HE4 after 3 or within the 6 planned cycles of chemotherapy is clearly associated with better overall survival in EOC. Patients with a HE4 plasma level >400pM at the end of chemotherapy have a particularly poor prognosis and could be immediately submitted to different chemotherapy regimens or be enrolled in perspective controlled clinical trials.