Ovarian cancer is the leading cause of death from gynecologic cancers, in fact, >80% of cases are diagnosed as advanced-stage disease associated with a high mortality rate (<40% of women cured). A systematic review was performed to estimate the role of HE4 in the diagnosis, prognosis and follow-up of ovarian tumors. Areas covered: A comprehensive search of the literature from January 1952 to August 2016 was conducted using the terms 'ovarian tumor' and 'ovarian cancer' combined with 'HE4' and 'human epididymis protein 4'. The search identified a total of 259 citations, of which 141 were potentially relevant after initial evaluation. Of these studies, 75 primary studies met the inclusion criteria and were analyzed, with a total of 14,773 patients. Expert commentary: Serum HE4 dosage is a useful preoperative test for predicting the benign or malignant nature of pelvic masses. It seems to have a promising role in the prediction of clinical and surgical outcomes. Moreover, HE4 seems to better predict recurrence in comparison to CA-125.
The aim of the study was to explore the clinical value of serum human epididymis secretory protein E4 (HE4) and CA125 in endometrial carcinoma. From January 2010 to April 2012, serum specimens were collected from consecutive cases of endometrial carcinoma and from cases of uterus benign disease (control group). The CA125 normal value is considered less than 35 U/mL. Two HE4 cutoff are considered: less than 70 pmol/L and less than 150 pmol/L. The specificity analysis was performed using the Mann-Whitney test for the CA125 and HE4 series. The level of statistical significance is set at p < 0.05. The sensitivity of CA125 in detecting endometrial cancer is 19.8 %, whereas the sensitivity of HE4 is 59.4 and 35.6 % for 70 and 150 pmol/L cutoff, respectively. Thus the specificity of HE4 is 100 % (positive predictive value = 100 %, negative predictive value = 71.52 and 61.31 % considering the two HE4 cutoff, respectively), whereas the CA125 specificity is 62.14 % (positive predictive value = 33.9 %, negative predictive value = 44.14 %) in detection of endometrial cancer. Combining CA125 and HE4, the sensitivity to detect endometrial cancer is 60.4 and 34.6 %, at HE4 cutoff of 70 and 150 pmol/L, respectively, with a specificity of 100 %. HE4 may be a new tool for preoperative evaluation and postoperative surveillance of endometrial cancer patients, with a positive predictive value = 100 %. HE4 at cutoff of 70 pmol/L yields the best sensitivity and specificity.
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