Human Epididymis Protein 4 (HE4 tumor marker) Is a Secreted Glycoprotein that Serous and Endometrioid Ovarian Carcinomas overexpress.
CA 125 is the most commonly used serum marker to monitor therapeutic response and detect disease recurrence in patients treated for epithelial ovarian cancer.
The National Comprehensive Cancer Network recommends CA 125 measurement before each treatment cycle and at each follow-up evaluation for women with elevated pretreatment concentrations. However, CA 125 is not elevated in all patients with epithelial ovarian cancer and is not specific to ovarian cancer. For this reason, physicians measure Human Epididymis Protein 4 (he4 tumour marker) in addition to CA 125.3 HE4 was first identified in the epithelium of the distal epididymis and originally predicted to be a protease inhibitor involved in sperm maturation.
HE4 marker overexpresses in 93 percent of serious, 100 percent of endometrioid epithelial ovarian cancers, and 50 percent of clear cell (not mucinous) ovarian carcinomas. HE4 secrete into the circulation resulting in elevated serum levels.
HE4 Tumour Marker Intro
Human epididymal protein 4 (HE4 Tumour Marker) is a novel ovarian cancer-specific tumor marker with higher specificity and sensitivity than cancer antigen 125 marker. HE4 is a secreted glycoprotein encoded by the WFDC2 gene with a molecular weight of about 25kD. It is mainly overexpressed in ovarian epithelial and endometrial cancer and has a specific positive rate in lung cancer and gastric cancer. Overexpression of HE4 can promote the proliferation, invasion, and metastasis of ovarian cancer cells. It consists of two core structures: a native N-terminal glycosylated protein of approximately 25KDa and two whey acidic protein core regions (WAP, consisting of 4 disulfide-bonded core regions and eight cysteine residues). The specificity and positive predictive value of HE4 detection alone were higher, and the combined detection of CA125 had higher sensitivity and significantly improved the negative predictive value and diagnostic accuracy. Human epididymal protein 4 (HE4) is a novel ovarian cancer-specific tumor marker with higher specificity and sensitivity than CA125. HE4 is a secreted glycoprotein encoded by the WFDC2 gene with a molecular weight of about 25kD. It is mainly overexpressed in ovarian epithelial and endometrial cancer and has a specific positive rate in lung cancer and gastric cancer. Overexpression of HE4 can promote the proliferation, invasion, and metastasis of ovarian cancer cells. It consists of two core structures: a native N-terminal glycosylated protein of approximately 25KDa and two whey acidic protein core regions (WAP, consisting of 4 disulfide-bonded core regions and eight cysteine residues). The specificity and positive predictive value of HE4 detection alone were higher, and the combined detection of CA125 had higher sensitivity and significantly improved the negative predictive value and diagnostic accuracy.
HE4 Tumor Marker Importance
Under normal physiological conditions, HE4 tumour marker has a deficient expression level in the human body. Still, it is highly expressed in ovarian cancer tissue and patient serum, and HE4 can be used for early diagnosis, identification, treatment monitoring, and prognosis evaluation of ovarian cancer. 88% of ovarian cancer patients will have elevated HE4 tumour marker. Compared with CA125, HE4 tumour marker is more sensitive and specific, especially in the initial asymptomatic stage of the disease. The diagnostic sensitivity of HE4 in the early stage of the disease was 82.7%, while that of CA125 was only 45.9%. The specificity of HE4 is as high as 99% compared to the specificity of CA125 of only 20%, which means that clinicians have more confidence in the HE4 test results. When a clinician diagnoses ovarian cancer solely based on a CA125 test, 8 out of 10 women may be misdiagnosed. HE4 and CA125 are complementary markers. The combined application of the two can increase the sensitivity to 92%, reduce false-negative results by 30%, and significantly increase the accuracy of an ovarian cancer diagnosis.
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