Human epididymis protein 4 (HE4) in benign and malignant diseases

Abstract

Background: Human epididymis protein 4 (HE4) is described as a useful new biomarker in ovarian cancer. As HE4 is neither tumor nor organ specifi c, we intensively investigated the occurrence of this protein in female and male patients with various benign and malignant diseases in order to avoid misinterpretation and to identify potential additional clinical relevance. Methods:We retrospectively investigated HE4 (ARCHITECT ® , Abbott Diagnostics, US) in the sera of 205 healthy individuals, 654 patients with benign disorders and 720 patients with cancer before initial treatment. Results:The lowest concentrations of HE4 were observed in healthy men (median 26.2 pmol/L) followed by healthy women (median 40.4 pmol/L). In benign diseases, highest HE4 concentrations were seen in both women and men with renal failure (women, median 1041 pmol/L; men, median 1368 pmol/L). In women, the highest HE4 levels in malignant diseases were observed in ovarian cancer (median 242 pmol/l), whereas the highest HE4 concentrations in men occurred in lung cancer (median 89.2 pmol/L). The area under the curve (AUC) of HE4 in women was highest in ovarian cancer and borderline tumors as compared to benign gynecological disorders (88.9 % ), with a sensitivity of 67.4 % at 95 % specifi city. Also, signifi cantly elevated concentrations of HE4 with reference to the respective group of benign diseases were observed

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

“…Generally, HE4 levels in healthy women are higher than those in healthy men (median 26.2 pM vs. 40.4 pM) presumably due to the HE4 expression in woman's reproductive organs. In both sexes, the HE4 levels appear to increase with age [36]. In a study by Bolstad et al, HE4 was measured in 1591 subjects comprised of 801 women and 790 men of age 18-86 years from the Nordic Reference Interval Project Bio-bank and Database.…”

“…Hertlein et al compared serum HE4 concentrations in patients with several benign gynecological diseases such as benign cervical diseases, cystadenoma, leiomyoma, bleeding disorder, endometriosis, functional ovarian cyst, and inflammation diseases [36]. They found that women with inflammation diseases had the highest median values of serum HE4 (median 67.6 pM).…”

Tissue CA125 and HE4 Gene Expression Levels Offer Superior Accuracy in Discriminating Benign from Malignant Pelvic Masses

“…HE4 was found to offer a better diagnostic performance than CA125 for distinguishing between benign and malignant pelvic masses (Holcomb et al, 2011;Zheng and Gao, 2012;Chung et al, 2013). Regardless of its beneficial characteristics, similar to classic tumor markers (Trapé et al, 2011), HE4 has some limitations in the detection of tumors, where its level may be elevated in benign diseases without evidence of malignancy (Hertlein et al, 2012).…”

Diagnostic value of human epididymis protein 4 (HE4) as a potential serological marker of endometrial cancer

“…[14] обнаружили повышенную экс-прессию НЕ4 не только в опухолевой ткани РЯ, но и не-которых других опухолей, в том числе и в РЭ. Результаты оценки НЕ4 как потенциального ОМ для РЭ противоре-чивы [7,[15][16][17][18]. В 2008 г. R. Moore и соавт.…”

“…[18]. В других публикациях приводятся данные о меньшей чувствительности НЕ4 для РЭ [16,17], и даже показано преимущество СА125 (50% против 28% -для НЕ4) [15].…”