Human epididymis protein 4: factors of variation

Background: Amongst the newly proposed biomarkers for ovarian cancer, serum human epididymis protein 4 (HE4) shows the greatest potential for clinical use. However, systematic appraisals of its biological characteristics are not available. This study sought to critically revise the available literature on biological and lifestyle factors affecting HE4 concentrations in serum to understand their possible influence on the marker interpretation. Methods: A literature search was undertaken on electronic databases and references from retrieved articles. Article results were analyzed by evaluating study design, sample size, statistical approach, employed assay and, when available, by collecting similar information for carbohydrate antigen 125 (CA-125). Results: Several factors may influence serum HE4 concentrations. In contrast to CA-125, higher HE4 concentrations are reported in the elderly. Although no variations in HE4 concentrations can be clearly associated to menopausal status, a strong difference in biomarker biological intra-individual variation according to the fertility status is reported. Smoking and renal function can also significantly influence HE4 results. Conclusion: The knowledge of factors influencing HE4 concentrations is relevant to promote more adequate interpretative criteria for use of this biomarker in the clinical setting.