Caratteristiche biochimiche e funzionali della proteina 4 dell’epididimo umano (HE4)

Serum carbohydrate antigen 125 (CA125) is the established biomarker for detecting ovarian cancer (OC) recurrence and monitoring therapeutic response. The recent evidence calls into question the better performance of serum HE4 to detect patients with OC. The replacement of CA125 with HE4 appears advisable, but more focus is needed on the biochemical characterization of the protein structure, which is an overriding prerequisite to overcome possible methodological limitations. By resorting to published literature, we sought to review the available information on the protein structure, activity, functions and tissue expression under physiologic and pathologic conditions. The gene encoding for HE4, WFDC2, is composed by six exons. Five HE4 isoforms have been identified and recognized to define specific patterns differently expressed in neoplasm and normal tissues. Under physiologic conditions, HE4 is reported as protease inhibitor playing a crucial role in sperm maturation. In pathophysiology, HE4 is likely involved in cancer progression and metastases. In particular, HE4 is overexpressed in serous and endometrioid OC. Further information on the HE4 expression pattern in cancer progression will likely improve the clinical performance of the marker.