Abstract 437: Lumipulse G HE4 assay for monitoring of ovarian cancer recurrence and progression
Authors: Radwan Rachel , Öhrvik Anders , Falcone Katherine , Gannon Sara , Felman Candice , Benina Natalya , Svensson Natascha , Raju Savitha , Jones Sharee , Peacock Catherine , Young Julianna , Li Zhong-Qian , Fermer Christian , Dickson Diana 
Published: July 2016

Human epididymis protein 4 (HE4), a member of Whey acidic four-disulfide core protein (WFDC) family, was demonstrated as one of the most useful biomarkers for ovarian cancer (HellstrÖm I, et al. 2003; Drapkin R, et al. 2005; Moore RG, et al. 2007).This study was to evaluate the use of Lumipulse G HE4 assay with patient serum for monitoring recurrence and progression of epithelial ovarian cancer. Recently, Lumipulse G HE4 assay was cleared by US FDA as an aid in monitoring recurrence or progressive disease in patients with epithelial ovarian cancer. Methods: Lumipulse G HE4 is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of HE4 in human serum and plasma on the Lumipulse G System by a two-step sandwich immunoassay method. In the assay, serum was added to and incubated with an anti-HE4 monoclonal antibody (MAb)-linked magnetic particles. The particles were then washed and rinsed to remove unbound materials. Alkaline phosphatase-labeled 2nd anti-HE4 MAb was added to and incubated with the HE4-bound particles. The particles were then washed and rinsed again to remove unbound materials. Substrate 3-(2’-spiroadamantane)-4-methoxy-4-(3”-phosphoryloxy) phenyl-1, 2-dioxetane disodium salt (AMPPD) solution was then added to and mixed with the particles. Luminescence signals were thus generated by the cleavage of dephosphorylated AMPPD and converted into the amount of HE4 in the serum. Results: In the monitoring study, changes in HE4 levels in serial serum samples collected in SST tubes from 72 subjects with epithelial ovarian cancer were compared to changes in disease status, that is, progression or no progression. A total of 330 observations were undertaken with an average number of 5.6 observations per subject. A positive change in the HE4 value was defined as an increase in the observation value that was at least 18% greater than the previous observation value. Of the 61 samples with a positive change, 49% of them correlated with the progression of epithelial ovarian cancer while 80% of the 269 subject serial samples with no significant change in the HE4 value correlated with no progression. The total concordance was 74%, positive predictive values (PPV) 35%, and negative predictive value (NPV) 87%. In addition, a comparison of Lumipulse G HE4 with the predicate device, HE4 EIA, was carried out using specimens consistent with CLSI Protocol EP09-A3 and weighted Deming regression analysis. The slope and correlation coefficient (r) obtained were 1.03 and 0.9891, respectively, for the tested specimens (n = 143) which ranged from 33.4 - 969.5 pmol/L, and slope and r of 1.03 and 0.9917, respectively, for the tested specimens (n = 168) ranged from 33.4 - 4602.0 pmol/L. Conclusion: The Lumipulse G HE4 assay has demonstrated to be useful in monitoring the course of disease in women with epithelial ovarian cancer and well correlated with the predicate device HE4 EIA.

Citation Format: Rachel Radwan, Anders Öhrvik, Katherine Falcone, Sara Gannon, Candice Felman, Natalya Benina, Natascha Svensson, Savitha Raju, Sharee Jones, Catherine Peacock, Julianna Young, Zhong-Qian Li, Christian Fermer, Diana Dickson. Lumipulse G HE4 assay for monitoring of ovarian cancer recurrence and progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 437.