Human epididymis protein 4 (HE4) is a whey acidic four-disulfide core protein. Serum HE4 has been shown to be a promising biomarker for epithelial ovarian cancer (EOC) with manual HE4 EIA assays. The ARCHITECT system is one of the major automated formats for cancer immunodiagnostics. This abstract describes the clinical performance of an investigational ARCHITECT HE4 assay in the measurement of serum HE4 from longitudinal samples of subjects with EOC and single-point samples from healthy subjects, and subjects with malignancy, benign diseases, EOC or other malignant diseases.

PROCEDURES: The ARCHITECT HE4 Assay is a paramagnetic microparticle chemiluminescent assay adopting the sensitive CHEMIFLEX® technology. Single-point and longitudinal serum samples were tested with an investigational ARCHITECT HE4 Assay reagent lot on the ARCHITECT i2000SR. Single-point sera were collected from healthy subjects (N = 400), subjects with pregnancy (N = 50) and benign disease (N = 612), and subjects which were diagnosed with EOC (N = 314) and other cancers (N = 250) including endometrial, breast, gastrointestinal, lung, and bladder cancer. Longitudinal sera (N = 506), including initial time point and follow-up visits (average = 5.7 per subject), were collected from subjects (N = 76) which were diagnosed with EOC. All of the single-point and longitudinal samples were handled in accordance with IRB-approved and GCP-compliant protocols.

RESULTS: Using an ARCHITECT HE4 cut-off value of >140 pmol/L, the percent distributions of ARCHITECT HE4 by cohort are: 3% of healthy subjects, 0% with pregnancy, 7.2% of subjects with benign diseases, 53.5% with EOC and 28.4% with other cancers. Using the upper 95% point of the distribution of the HE4 ratio at 14% to categorize the successive HE4 readings into those that were and were not significantly elevated for the longitudinal samples, the sensitivity, specificity and positive predictive value of HE4 elevation versus disease progression were 53.4% (95% CI: 44.1%-62.5%), 78.8% (95% CI: 74.7% - 82.4%) and 43.2% (95% CI: 32.9% - 54.1%) respectively. The total concordance between HE4 elevation and disease progression was 73%. Receiver Operator Characteristic analysis showed an area under the curve of 0.685 (SE = 0.033) for the diagnosis of progression from the ratio of successive HE4 readings. When comparing the change of the HE4 ratio with the diagnostic response to therapy, a decrease in HE4 reflected response to therapy with a sensitivity of 82% and a specificity of 53%.

CONCLUSIONS: The study with single-point samples has shown the utility of ARCHITECT HE4 values as a serum biomarker for EOC. The longitudinal increase of ARCHITECT HE4 values in sera seemed to be effective in recognizing the progression of EOC. The longitudinal decrease of ARCHITECT HE4 values in sera seemed to correlate with the response of EOC subjects to therapy.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4653.