Human epididymis protein 4 (HE4) in laboratory medicine and an algorithm in renal disorders

Over the past three decades, cancer antigen (CA) 125 has been utilized for monitoring women who were treated for ovarian cancer. However, this tumor marker showed several limitations such as false elevation in benign pelvic diseases and, in turn, no alterations in ovarian tumors at early stages with a relatively high ratio. For more than ten years, the human epididymis protein 4 (HE4) has become available for the routine laboratory repertoire, showing a higher sensitivity and specificity compared to that of CA125 in ovarian malignancies, but also in other types of tumors based on recently accumulated clinical data. Despite its remarkable diagnostic characteristics, in certain cases, the evaluation of HE4 results may be problematic when patients suffer from additional conditions that may alter HE4 level. Besides the direct effects of age and smoking, menopause status and decreased renal function also show a substantial impact on HE4 values, which should be considered in each patient. For this purpose, we attempted to create a new formula and an algorithm that may be helpful to predict the probability of the presence of ovarian tumor by using the concentrations of HE4 and CA125.