A critical review on HE4 performance in endometrial cancer: where are we now?

To date, no good marker for endometrial cancer (EC) that may be routinely used in clinical practice for diagnosis, prognosis and monitoring is available; besides the use of tumour markers is not recommended by international guidelines. However, during the last years, an increasing interest in literature has been growing on human epididymis protein 4 (HE4) that demonstrated to be a useful clinical marker with high sensitivity and specificity even at early stage. However, published studies differ for some variables such as HE4 cut-off and sample size. Therefore, we assess this comprehensive review to gather all the evidence reported in literature on HE4 potential value in diagnosis, prognosis, and recurrence of EC. A systematic literature search was performed using PubMed/PubMed Central/MEDLINE predefined keywords from January 1952 to June 2013. We divided all the relevant studies into three different clinical issues: "Diagnosis", "Prognosis" and "Disease monitoring". The analysis of published data suggests that HE4 is the most accurate and sensitive EC marker identified to date. In particular, this new marker seems to have a good performance in diagnosis. The best cut-off of HE4 in diagnosis ranges between 50 and 70 pmol/L, resulting at least in 78.8 % of sensitivity and 100 % of specificity in all stages. Another important aspect to consider is HE4 capacity in predicting the stage of disease and myometrial involvement, which can help scheduling the appropriate timing of imaging and surgery in a more individualised fashion and as indicator of patients prognosis.