A new marker for breast cancer diagnosis, human epididymis protein 4: A preliminary study

Abstract

Breast cancer is the most frequently diagnosed cancer type in women. Tumor markers have been widely used for assessing the treatment response and early diagnosis of recurrence. Human epididymis protein 4 (HE4) is expressed in ductal carcinoma of the breast tissue; however, its serum levels and their diagnostic and prognostic potential in breast cancer have not been investigated, which was therefore the aim of the present study. The serum levels of HE4 were determined in 36 breast cancer patients, 11 ovarian cancer patients and 16 healthy volunteers. The association between clinicopathological characteristics of breast cancer and serum HE4 levels was investigated. A significant difference in the median serum levels of HE4 was identified between breast cancer patients, ovarian cancer patients and healthy volunteers (P=0.013). The cutoff value for the prediction of breast cancer was determined at >13.24 pmol/l for HE4, with a sensitivity of 61.11%, specificity of 68.75%, positive predictive value of 81.48%, negative predictive value of 44.0% and accuracy of 63.46%. Furthermore, a positive correlation between the serum levels of HE4 and cancer antigen 15-3 was determined (r=0.399, P=0.026). To the best of our knowledge, the present study was the first to determine the diagnostic value of serum HE4 for breast cancer. A significant elevation of serum HE4 levels in patients with breast cancer compared with that in healthy controls was identified. HE4 may serve as a novel biomarker for the diagnosis of breast cancer.

Tissue expression of human epididymal secretory protein 4 may be useful in the differential diagnosis of uterine cervical tumors

“…Because CA 125 is often elevated in benign conditions or as a result of physiologic changes in premenopausal women, it has not any confirmed role in the early detection of gynecologic cancers. Since abnormal levels of HE4 have been less frequently encountered in benign gynecological conditions HE4 may have increased specificity in differentiating between benign and malignant conditions [2][3][4][5][6][7]. In the present study, we have found that HE4 tissue expression increased in carcinomas, but decreased in intraepithelial neoplasia.…”

“…The potential use of HE4 as a tumor marker has been supported by an increasing number of studies demonstrating an upregulation of HE4 in a range of malignant neoplasms, particularly of gynecological, pulmonary and gastrointestinal origin [3,12,13,16,17,21]. Serological tests have revealed that HE4 has increased sensitivity and specificity in the detection of ovarian cancer relative to CA 125, which is the current gold standard serum biomarker for ovarian carcinomas [3,12]. Several studies examining multiple serum biomarkers for epithelial ovarian carcinomas have found the combination of HE4 and CA125 had greater sensitivity and specificity than either marker alone.…”

“…Conversely, HE4 overexpression has not been detected in ovarian mucinous tumors [4][5][6], non-epithelial ovarian cancers, sex cord stromal tumors and germ cell tumors. However overexpression of HE4 has been detected in primary tuba uterina carcinomas and endometrial malignancies [2][3][4][5][6][7]. Among non-gynecological cancers, HE4 expression has been also demonstrated in various subtypes of lung cancer [12].…”

“…HE4 contains four disulfide core proteins and due to similarities with other whey acidic protein family members, it functions as a proteinase inhibitor [2,3]. Firstly, presence of HE4 in the distal regions of the epithelial cells of the epididymal duct, suggests its roles in sperm maturation [1][2][3][4][5].…”

Diagnostic value of urinary-to-serum human epididymis protein 4 ratio in ovarian cancer

“…For example, a large study demonstrated that S-HE4 has a higher sensitivity and specificity in the diagnosis of OC when compared with serum CA-125 (23). However, the evaluation of S-HE4 levels may be problematic when patients suffer from additional conditions, such as CKD (17), heart failure (4), and breast (24) and lung (25) cancer. Thus, the accuracy of S-HE4 in OC diagnosis remains a challenge.…”